益生菌Lactobacillus casei Zhang免疫调节和抗肿瘤作用及机理研究
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摘要
本课题以内蒙古农业大学乳品生物技术与工程教育部重点实验室从传统发酵酸马奶中分离鉴定的240株乳杆菌中,经前期大量实验确立的一株具有明显益生特性的乳杆菌Lactobacillus. casei Zhang(Lb. casei Zhang)为研究对象,观察了其对实验小鼠的的免疫调节及抗肿瘤作用,并探讨了其可能的作用机理。
前期的大量研究表明,益生菌Lb. casei Zhang具有优良的益生特性和降胆固醇、抗氧化和免疫调节等对机体有益的功能特性。
本课题以前期的研究为基础,深入探讨了益生菌Lb. casei Zhang免疫调节及抗肿瘤方面的功能特性,为其进一步开发应用提供了实验依据。
本课题实验分四部分:
第一部分:采用动物活体试验方法,Lb. casei Zhang制备成热致死菌体和活菌制剂各分成高、中、低三个剂量组灌服小鼠15天,测定胸腺指数、脾脏指数;观察ConA促进脾淋巴细胞增殖作用、脾脏巨噬细胞吞噬中性红的能力。采用ELISA法检测血清中IFN-γ、IL-12、IL-1α、TNF-α的含量。
第二部分: Lb. casei Zhang活菌制剂分高、中、低三个剂量组灌服小鼠。分别于第3、7、11、15天,摘取脾脏,计算脾指数;RT-PCR法测定脾脏中IL-2和IL-2RαmRNA的转录水平,并从小鼠局部肠粘膜免疫组织及免疫细胞着手,对服用Lb. casei Zhang后小鼠肠道局部免疫组织一Peyer’s结的数量计分进行了研究。采用免疫组化法检测小肠粘膜CD3+、IgA+细胞数量并通过图象分析软件分析其阳性信号平均光密度值了解其表达情况。
第三部分:以荷H22肝癌小鼠为模型,用Lb. casei Zhang活菌制剂分高、中、低三个剂量灌服小鼠12天后,滴片法测定小鼠腹腔巨噬细胞吞噬鸡红细胞的吞噬率和吞噬指数;计算脾指数,计算肿瘤生长抑制率,ELISA法测定血清中肿瘤坏死因子-β(TNF-β)的含量;免疫组化法检测小鼠肿瘤细胞中癌基因Bcl-2和抑癌基因Bax蛋白的表达程度,从分子水平探讨其抗肿瘤的可能机制。
第四部分:以荷H22肝癌化疗小鼠为模型,观察Lb. casei Zhang对化疗药物的减毒增效作用。以腹腔注射环磷酰胺(CTX)联用Lb. casei Zhang活菌制剂高、中、低三个剂量灌服小鼠12天后,计算脾指数、肿瘤生长抑制率,并对小鼠肠道局部免疫组织一Peyer’s结进行计数计分;采用原位杂交法检测肿瘤细胞中增殖细胞核抗原(PCNA)的表达,采用碘化丙啶(PI)染色利用流式细胞仪检测肿瘤细胞细胞周期及凋亡率。
通过以上的实验结果,我们得出的总体结论是:具有明显益生特性的乳杆菌Lb. casei Zhang对实验小鼠的细胞免疫、体液免疫、肠道粘膜免疫可产生多方面的、有利于机体免疫功能状态的调节作用;对体外移植性小鼠肝癌H22肿瘤具有明显的抑制生长作用,对化疗药环磷酰胺(CTX)具有明显的减毒增效作用,其抗肿瘤的机制可能是通过增强荷瘤小鼠的免疫功能、抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡而发挥作用。
On the basis of the research on the 240 strains of Lactobacillus. casei Zhang(Lb. casei Zhang)isolated from the traditionally home-made koumiss by the Key Laboratory of Dairy Biotechnology and Engineering of Inner Mongolia Agricultural University affiliated to the Ministry of Education. This thesis studies the function of immunity adjustment and anti-tumor activity of one strain of probiotic bacterium Lb. casei Zhang in the body of a laboratory mouse, which contains the potential probiotic properties proved in many past experiments, and explores its possible mechanism of activity.
According to the rich studies in the early stage, it is proved that the Lb. casei Zhang has good probiotic properties, and some functions such as reducing cholesterin, antioxidation, and immune adjustment as well as other properties.
Based on the studies in the early stage, this thesis further explores the immunity adjustment and anti-tumor activity of Lb. casei Zhang, and then lays a foundation of research in experiment for its further development and application.
The experiment on this thesis consists of four parts:
Part I:
Taking the in vivo experiment, several little mice are orally taken the bacillus killed by high heat and live bacillus made from Lb. casei Zhang in three dosages with high dose, middle dose and low dose and observed for 15 days. Measure the thymus index and spleen index of the mice; observe the function and ability of ConA in the lymphocyte multiplication and macrophage phagocytic function. Test the content of IFN-γ, IL-12, IL-1αand TNF-αin the blood serum in the method of ELISA.
Part II:
Live bacillus of Lb. casei Zhang is divided into three dosage of high, middle and low and instilled into the mice. And then remove their spleens to calculate the index of spleens at the third, seventh, eleventh and fifteenth day. Take the RT-PCR method to measure the transcription level of IL-2 and IL-2RαmRNA in the spleens.
Set about the research on the immune tissue and immune cells of local intestinal mucosa of little mice, study the number counting of Peyer’s in the local intestine immune tissue of mice taken Lb. casei Zhang, measure the number of CD3+ and IgA+ of small intestine mucous by the method of immune histochemistry, and then analyze the average optical density with positive signal by using image analysis system so as to know its expressive condition.
Part III:
Take the little mice with H22 liver cancer for example, 12 days later when the mice are instilled into live bacillus of Lb. casei Zhang in three dosages of high, middle and low, and measure the rate and index of peritoneal macrophage phagocytizing chicken red blood cell in mice by drop technique and calculate the index of spleen and the rate of tumor suppression. Measure the number of Tumor Necrosis Factorβin blood serum by the method of ELISA, check the expression of cancer bcl-2 gene and tumor suppressor gene by immune histochemistry methods, and then explore the possible mechanism of tumor suppressor based on the molecule level.
Part IV:
Take the mice with H22 liver cancer treated by chemical therapy as models, and then observe the action of toxin-attenuating and efficacy– enhancing caused by Lb. casei Zhang. 12 days later when the mice are injected with Cyclophosphamide in the abdomen and together instilled into live bacillus of Lb. casei Zhang in three dosages of high, middle and low, calculate the index of spleen and rate of tumor suppression, record the Peyer’s in the local immune tissue of mice’s intestine, check the expression of PCNA in tumor cells by using the method of in situ hybridization, and check the cell cycle and apoptosis rate of tumor cells by using flow cytometer with propidium iodide technology.
We reach a general conclusion based on the above experiments: the Lb. casei Zhang with evident probiotic properties have many active adjustment actions on cell immunity, humoral immunity and intestine mucosal immunity of laboratory little mice; have an evident inhibitory action of growth on the transplanted tumor of H22 liver cancer-bearing mice; have an evident action of toxin-attenuating and efficacy– enhancing on the Cyclophosphamide in chemical therapy. Its mechanism to resist tumor probably is to inhibit the increase of tumor cells and induce the apoptosis of tumor cells through strengthening the immunity of mice with tumor.
前期的大量研究表明,益生菌Lb. casei Zhang具有优良的益生特性和降胆固醇、抗氧化和免疫调节等对机体有益的功能特性。
本课题以前期的研究为基础,深入探讨了益生菌Lb. casei Zhang免疫调节及抗肿瘤方面的功能特性,为其进一步开发应用提供了实验依据。
本课题实验分四部分:
第一部分:采用动物活体试验方法,Lb. casei Zhang制备成热致死菌体和活菌制剂各分成高、中、低三个剂量组灌服小鼠15天,测定胸腺指数、脾脏指数;观察ConA促进脾淋巴细胞增殖作用、脾脏巨噬细胞吞噬中性红的能力。采用ELISA法检测血清中IFN-γ、IL-12、IL-1α、TNF-α的含量。
第二部分: Lb. casei Zhang活菌制剂分高、中、低三个剂量组灌服小鼠。分别于第3、7、11、15天,摘取脾脏,计算脾指数;RT-PCR法测定脾脏中IL-2和IL-2RαmRNA的转录水平,并从小鼠局部肠粘膜免疫组织及免疫细胞着手,对服用Lb. casei Zhang后小鼠肠道局部免疫组织一Peyer’s结的数量计分进行了研究。采用免疫组化法检测小肠粘膜CD3+、IgA+细胞数量并通过图象分析软件分析其阳性信号平均光密度值了解其表达情况。
第三部分:以荷H22肝癌小鼠为模型,用Lb. casei Zhang活菌制剂分高、中、低三个剂量灌服小鼠12天后,滴片法测定小鼠腹腔巨噬细胞吞噬鸡红细胞的吞噬率和吞噬指数;计算脾指数,计算肿瘤生长抑制率,ELISA法测定血清中肿瘤坏死因子-β(TNF-β)的含量;免疫组化法检测小鼠肿瘤细胞中癌基因Bcl-2和抑癌基因Bax蛋白的表达程度,从分子水平探讨其抗肿瘤的可能机制。
第四部分:以荷H22肝癌化疗小鼠为模型,观察Lb. casei Zhang对化疗药物的减毒增效作用。以腹腔注射环磷酰胺(CTX)联用Lb. casei Zhang活菌制剂高、中、低三个剂量灌服小鼠12天后,计算脾指数、肿瘤生长抑制率,并对小鼠肠道局部免疫组织一Peyer’s结进行计数计分;采用原位杂交法检测肿瘤细胞中增殖细胞核抗原(PCNA)的表达,采用碘化丙啶(PI)染色利用流式细胞仪检测肿瘤细胞细胞周期及凋亡率。
通过以上的实验结果,我们得出的总体结论是:具有明显益生特性的乳杆菌Lb. casei Zhang对实验小鼠的细胞免疫、体液免疫、肠道粘膜免疫可产生多方面的、有利于机体免疫功能状态的调节作用;对体外移植性小鼠肝癌H22肿瘤具有明显的抑制生长作用,对化疗药环磷酰胺(CTX)具有明显的减毒增效作用,其抗肿瘤的机制可能是通过增强荷瘤小鼠的免疫功能、抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡而发挥作用。
On the basis of the research on the 240 strains of Lactobacillus. casei Zhang(Lb. casei Zhang)isolated from the traditionally home-made koumiss by the Key Laboratory of Dairy Biotechnology and Engineering of Inner Mongolia Agricultural University affiliated to the Ministry of Education. This thesis studies the function of immunity adjustment and anti-tumor activity of one strain of probiotic bacterium Lb. casei Zhang in the body of a laboratory mouse, which contains the potential probiotic properties proved in many past experiments, and explores its possible mechanism of activity.
According to the rich studies in the early stage, it is proved that the Lb. casei Zhang has good probiotic properties, and some functions such as reducing cholesterin, antioxidation, and immune adjustment as well as other properties.
Based on the studies in the early stage, this thesis further explores the immunity adjustment and anti-tumor activity of Lb. casei Zhang, and then lays a foundation of research in experiment for its further development and application.
The experiment on this thesis consists of four parts:
Part I:
Taking the in vivo experiment, several little mice are orally taken the bacillus killed by high heat and live bacillus made from Lb. casei Zhang in three dosages with high dose, middle dose and low dose and observed for 15 days. Measure the thymus index and spleen index of the mice; observe the function and ability of ConA in the lymphocyte multiplication and macrophage phagocytic function. Test the content of IFN-γ, IL-12, IL-1αand TNF-αin the blood serum in the method of ELISA.
Part II:
Live bacillus of Lb. casei Zhang is divided into three dosage of high, middle and low and instilled into the mice. And then remove their spleens to calculate the index of spleens at the third, seventh, eleventh and fifteenth day. Take the RT-PCR method to measure the transcription level of IL-2 and IL-2RαmRNA in the spleens.
Set about the research on the immune tissue and immune cells of local intestinal mucosa of little mice, study the number counting of Peyer’s in the local intestine immune tissue of mice taken Lb. casei Zhang, measure the number of CD3+ and IgA+ of small intestine mucous by the method of immune histochemistry, and then analyze the average optical density with positive signal by using image analysis system so as to know its expressive condition.
Part III:
Take the little mice with H22 liver cancer for example, 12 days later when the mice are instilled into live bacillus of Lb. casei Zhang in three dosages of high, middle and low, and measure the rate and index of peritoneal macrophage phagocytizing chicken red blood cell in mice by drop technique and calculate the index of spleen and the rate of tumor suppression. Measure the number of Tumor Necrosis Factorβin blood serum by the method of ELISA, check the expression of cancer bcl-2 gene and tumor suppressor gene by immune histochemistry methods, and then explore the possible mechanism of tumor suppressor based on the molecule level.
Part IV:
Take the mice with H22 liver cancer treated by chemical therapy as models, and then observe the action of toxin-attenuating and efficacy– enhancing caused by Lb. casei Zhang. 12 days later when the mice are injected with Cyclophosphamide in the abdomen and together instilled into live bacillus of Lb. casei Zhang in three dosages of high, middle and low, calculate the index of spleen and rate of tumor suppression, record the Peyer’s in the local immune tissue of mice’s intestine, check the expression of PCNA in tumor cells by using the method of in situ hybridization, and check the cell cycle and apoptosis rate of tumor cells by using flow cytometer with propidium iodide technology.
We reach a general conclusion based on the above experiments: the Lb. casei Zhang with evident probiotic properties have many active adjustment actions on cell immunity, humoral immunity and intestine mucosal immunity of laboratory little mice; have an evident inhibitory action of growth on the transplanted tumor of H22 liver cancer-bearing mice; have an evident action of toxin-attenuating and efficacy– enhancing on the Cyclophosphamide in chemical therapy. Its mechanism to resist tumor probably is to inhibit the increase of tumor cells and induce the apoptosis of tumor cells through strengthening the immunity of mice with tumor.
引文
1周德庆.微生物学教程(第二版).北京:高等教育出版社,2004,39-60
2黄秀梨主编.微生物学(第二版).北京:高等教育出版社,2003
3郭本恒主编.益生菌.北京:化学工业出版社,2004
4凌代文.乳酸细菌分类鉴定及实验方法.北京:中国轻工业出版社,1999
5孟昭赫.乳酸菌与人类健康.北京:人民卫生出版社,1993
6郭兴华.益生菌基础与应用.北京:北京科学技术出版社,2002
7杨汝德,林勉,陈惠音.益生素及其应用.中国乳品工业,2000,28(1),29-31
8 Gionchetti P, Rizzello F, Venturi A, etal. Oralbacterio the rapyas mainte nancetrea tmentinp at ients with chronic pouchhitis:Adou-ble-blind,placebo-controlledtrial.Gastroenterology,2000,119:1512-1517.
9张自德,冯燕.蜡样芽抱杆菌活菌制剂治疗婴幼儿及成人腹泻60例临床观察.中国微生态学杂志,1999,6(3):177-180
10蓝景刚,胡宏.双歧杆菌及其表面分子的免疫增强作用.中国微生态学杂志,1999,11(3):129-131
11王树山,杨松,邓莉,等.微生态制剂“妈咪爱”治疗婴幼儿轮状病毒肠炎的临床研究.中国微生态学杂志,1996,8(3):31-33
12赖新峰,王立生,潘令嘉,等.双歧杆菌对裸鼠的腹腔巨噬细胞激活作用的初步观察.中国微生态学杂志,1999,11(6):336-337
13 Clausen M.R. ,H.,Tvede,M.,and Mortensen, P.B.(1991). Colonic Fer-mentationto Short-chain Fatty Acidsis decrease dinantibiotic -asso- ciateddia rrhea.Gastroenterology 101,1497-1504
14 Survival of Lactob qacillusaci do philusinaspray- dryingprocess Es-pina & Packard.J. Food protect 42: 149-152
15何国庆,孔青,等.益生菌的功效与潜在危害[J].食品科技,2004(1):12-15
16李琴,张世春,等.益生菌营养及保健作用[J].食品研究与开发,2004,25(2):106-109
17 Serum cholesteroland bowelflorain thenew born Harrison&peat.1975,Am J Clin.nutr,28:1351-1355
18杨维军,王华,等.益生菌的功效及其在食品中的应用[J].四川食品与发酵,2005(1):27-30
19 Pouwels.,P.H.Leer,R.J.Shaw.M,etal.Lactic acid bactria as antigen delivery vehickes for oral immunization purpose.Int.J.FoodTechnol41,1998:155-167
20董珂,刘晶晶,等.益生菌增强集体免疫和抗肿瘤作用的分子机制[J].中国微生态学杂,2005,17(1):79-81
21蒋寒青,康白.肠道生理性细菌粘附机制的研究进展.中国微生态学杂志,1995(1):48-49
22钟燕.益生菌与乳糖不耐受研究进展.国外医学卫生学分册,2003,30(2):101-105
23郑跃杰,潘令嘉,王立生,等.双歧杆菌粘附素的纯化.中华微生物和免疫学杂志,1999,19(3):1961
24苏世彦.双歧杆菌的分离、鉴定与驯化.江苏食品与发酵,1998(2):10-13
25田允波,葛长荣,张曦.益生素的研究和应用现状.兽药与饲料添加剂,1999,4(3):36-39
26张自德,冯燕.蜡样芽抱杆菌活菌制剂治疗婴幼儿及成人腹泻60例临床观察.中国微生态学杂志,1999,6(3):177-180
27 GILL HS,RUTHERFURD KJ,et al.Enhancement of natural and acquired immunity by Lactobacillus rhamnosus (HN001),Lactobacillus acidophilus (HN017) and Bifidobacterium lactis (HN019)[J].Br J Nutr.2000 Feb,83(2):167-176
28 HALLER D,SERRANT P,PERUISSEAU G,et al.IL-10 producing CD14low monocytes inhibit lymphocyte-dependent activation of intestinal epithelial cells by commensal bacteria[J].Microbiol Immunol,2002,46(3):195-205
29 CANGEMI de Gutierrez,RV,SANTOS de Araoz,ME NADER-MACIAS.Effect of intranasal administration of Lactobacillus fermentum on the respiratory tract of mice[J].Biol Pharm Bull,2000,23:973-978
30 CANGEMI de Gutierrez R,SANTOS V,NADER-MACIAS ME.Protective effect of intranasally inoculated Lactobacillus fermentum against Streptococcus pneumoniae challenge on the mouse respiratory tract[J].FEMS Immunol Med Microbiol,2001 ,31(3):187-195
31 MARIN ML,TEJADA-SIMON MV,LEE J H,et al.Stimulation of cytokine production in clonal macrophage and T-cell models by Streptococcus thermophilus:comparison with Bifidobacterium sp.and Lactobacillus bulgaricus[J].J Food Prot, 1998, 61: 859 -864
32 PELTO L,ISOLAURI E,LILIUS EM,et al.Probiotic bacteria down-regulate the milk-induced inflammatory response in milk- hypersensitive subjects but have an immunostimulatoryeffectin healthy subjects[J].Clin Exp Allergy,1998,28:1474-1479
33 TAKAGI AT,MATSUZAKI M,SATO K,et al.Enhancement of natural killer cytotoxicity delayedmurinecarcinogenesisbyaprobioticmicroorganism[J].Carcinogenesis,2001,22:599-605
34 HALLER D,SERRANT P,GRANATO D,et al.Activation of Human NK Cells by Staphylococci and Lactobacilli Requires Cell Contact-Dependent Costimulation by Autologous Monocytes[J].Clinical and Diagnostic Laboratory Immunology,2002,9(3):649-657
35 HANNE R.Lactobacilli Differentially Modulate Expression of Cytokines and Maturation Surface Markers in Murine Dendritic Cells [J]. The Journal of Immunology,2002,168:171-178.
36 SHIDA KK,MAKINO A,MORISHITA K,et al.Lactobacillus casei inhibits antigen-induced IgEsecretion through regulation of cytokine production in murine splenocyte cultures[J].Int Arch Allergy Immunol,1998.
37 LIM BK,MAHENDRAN R,LEE YK,et al.Chemopreventive effect of Lactobacillus rhamnosus on growth of a subcutaneously implanted bladder cancer cell line in the mouse[J].Jpn J Cancer Res,2002 ,93(1):36-41
38 De WAARD R,CAASSEN E,BOKKEN GC,et al.Enhanced Immunological Memory Responses to Listeria monocytogenes in Rodents, as Measured by Delayed-Type Hypersensitivity (DTH),Adoptive Transfer of DTH, and Protective Immunity, following Lactobacillus casei Shirota Ingestion Clinical and Diagnostic Laboratory Immunology, 2003,10(1):59-65
39 De Waard R, GARSSEN J,SNEL J,et al.Enhanced antigen-specific delayed-type hypersensitivity and immunoglobulin G2b responses after oral administration of viable Lactobacillus casei YIT9029 in Wistar and Brown Norway rats[J].Clin Diagn Lab Immunol,2001,8:762-767
40 HORI T,KIYOSHIMEA J,SHIDA K,et al.Augmentation of Cellular Immunity and Reduction of Influenza Virus Titer in Aged Mice Fed Lactobacillus casei Strain Shirota[J].Clinical and Diagnostic Laboratory Immunology,2002,9(1):105-108
41 POCHARD P,GOSSET P,et al.Lactic acid bacteria inhibit TH2 cytokine production by mononuclear cells from allergic patients [J].J Allergy Clin Immunol,2002 ,110(4):617-623.
42 PERDIGON G,ALVAREZ S,RACHID M,et al.Immune system stimulation by probiotics[J].J Dairy Sci,1995,78:1597-160
43 Blum S,Alvarze S and Haller D.Intestinal microflora and the interaction with immunocompetent cells.Antonie van Leeuwenhoek,1999,76:199-205
44王立生.双歧杆菌的免疫激活作用及其生物学意义.国外医学生理,病理科学与临床分册,1998,18(4):320-322
45 Lee J,Ametani A,Enomoto A,et al.Motoshima H:Ike F and Kaminogawa S.Screening for the immunopotentiatng activity of food microorganisms and enhancement of the immune response by Bifidobacterium adolescentis M101-4.Bioscience,Biotechnology and Biochemistry,1993,57:2127-2130.
46 Tejado-Simon MV,Lee JH,Ustunol Z,et al.Ingestion of yogurt containing Lactobacillus acidophilus and Bifidobacterium to potentiate immunoglobulin A response to choleratoxin in mice.Journal of Dairy Science.1999,82:649-660
47 Takahashi T,Oka T,Iwana H,et al.Immune Response of Mice to Orally Administcred LacticAcidbacteria. Bioscience. BiotechnologyandBiochemistry.1993,57(9):1557-1560
48 Marin ML,Lee JH,Murtha J,et al.Differential cytokine production in clonal macrophageand T cell lines cultured with Bifidobacterium sp.Journal of Dairy Science,1997,80:2713-2720
49 Perdigon G.Systemic augmentation of the immune response in mice by feeding ferment edmilk swith Lactobacillus casei and Lactobacillus acid ophilus.1988,Immunology 63:17-21
50 Maassen CB,Yamazaki R and Hashimoto S,et al.The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice.Journal of Dairy Science,1998,81(1):48-53.
51 Shida K,Makino K and Morishita A.Lactobacillus casei Inhibits Antigen-Induced IgE Secretion through Regulation of Cytokine Production in Murine Splenocyte Cultures.International Archives of Allergy and Immunology,1998.115(4):278-287
52 Matsuzaki T,Yamazaki R and Hashimoto S.The effect of oral feeding of Lactobacillus casei Shirota on immunoglobulin E production in mice.Joumal of Dairy Science.1998.81(1):48-53
53 Marin ML,Tejada-Simon MV,and Lee JH.Stimulation of cytokine production in clonal macrophage and T-cell models by Streptococcus thermophilus:Comparison with Bifidobacterium sp.and Lactobacillus bulgaricus Joumal of Food Protection,1998,61(7):859-864
54 Miettinen M,Matikainen S and Vuopio-Varkila J,et al.Lactobacillus and Streptococci Induce Interleukin-12(IL-12).IL-18,and Gamma Interferon Production in Human Peripheral Blood Mononuclear Cells.Infection and Immunity,1998,66(12):6058-6063
55 Perdigon G,Nader De Macios,M and Alvarez S,et al.Enhancement of immune response in mice fed with Streptococcus thermophilus and Lactobacillus acidophilus.Journal of Dairy Science, 1987, 70: 919-926
56 Zhan Y and Cheers C.Differential induction of macrophagederived cytokines by live and dead intracellular bacteria in vitro.Infection and Immunity,1995,63(2):720-723
57 Marin ML,Tejada-Simon MV,Murtha J,et al.Efeects of Lactobacillus spp on cytokine production byraw 264.7 macrophage and EL-4 thymoma cell lines.Journal of Food Protection, 1997, 60(11): 1364-1370
58 Perdigon G,Nader De Macios M,Alvarez S,et al.Efeect of perorally administered lactobacilli on macrophage activation in mice.Infection and Immunity,1986,53:404-410
59 Perdigon G,Nader De Macias ME,Alvarez S,et al.Enhancement of immune response in mice fed with Streptococcus thermophilus and Lactobacillus acidophilus.Journal of Dairy Science, 1987, 70: 919-926
60 Hatcher GE and Lambrecht RS.Augmentation of microphage phagocytic activity bycell-free extracts of selected lactic acid-producing bacteria.Journal of Dairy Science,1993,76:2485-2492
61 Muller-Alouf H,Alouf J,Gerlach D,et al.Comparative study of cytokine release by human peripheral blood mononuclear cells stimulated with Streptococcus pyogenes superantigeic erythrogenic toxins heat-killed Streptococci,and lipopolysaccharide.Infection and Immunity,1998,62(11):4915-4921
62 Tejada-Simon MV,Ustunol Z and Pestka JJ.Exvivo effects of lactobacilli,streptococci,and Bifidobacteria on cytokine and nitric oxide production in a murine model.Journal of Food Protection,1999,62(2):162-169
63 De Simone C and Vesely R.Enhancement of immune response of murine Peyer’s patches by a diet supplemented with yogurt.Immunopharrnacology and Immunotoxicology,1987,9(1):87-100
64 Trapp CL,Chang CC,Halpern GM,et al.The influence of chronic yogurt consumption on populations of young and elderly adults.Intemational Journal of Immunophannacology,1993,9:53-64.
65 Matsuzaki T,Yamazaki R,Hashimoto S,et al.Antidiabelic effects of an oral administration of Lactobacillus casei in a non-insulin-dependent diabetes mellitus (NIDDM) model using KK-A super(y) mice.Endocrine Journal,1997,44(3):357-365
66 Muscettola M,Massai L,Tanganelli C,et al.Effects of Lactobacilli on interferon production in young and aged mice.Annals New York Academy of Scienecs,1994,717:227-232
67 Chen T,Isomaki P,Rimpilainen M,et al.Human cytokine responses induced by gram-positive cell walls of normal intestinal microbiota.Clinical and Experimental Immunology,1999,118(2):261-267.
68 Tejada-Simon MV and Pestka JJ.Proinflammatory cytokine and nitric oxide induction in murine macrophages by cell wall and cytoplasmic extracts of lactic acid bacteria.Journal of Food Protection.1999,62(12):1435-1444
69 Perdigon G,Alvarez S,Rachid M,et al.Symposium:Probiotic bacteria for humans:clinical systems for evaluation of effectiveness.Journal of Dairy Science 1993,78:1597-1606
70 Popova P and Guencheva G.Lactobacillus Stimulating effect of deodan(an oral preparation from Lactobacillus bulgarcus“LB51”)on monocytes/macrophages and host resistance to experimental infections.International Journal of Immunopharmacology,1993,15:25-27
71 Morata de Ambrosini V,Gonzalez S,Perdigon G,et al.Immunostimulating Activity of Cell Walls from Lactic Acid Bacteria and Related Species.Food and AgriculturalImmunology.1998,10(2):183-191.
72 Tejada-Simon MV.Ustunol Z and Pestka JJ.Effects of Lactic acid bacteria ingestion of basal cytokine mRNA and immunoglobulin levels in mouse.Journal of Food Protection.1999,62(3):287-291.
73 Ha CL,Lee JH,Zhou HR,et al.Efeects of yogurt ingestion on mucosal and systemic cytokine gene expression in the mouse.Journal of Food Protection.1999,62(2):181-188
74 Spanhaak S,Havenaar R and Schaafsma G.The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans.European Journal of Clinical Nutrition,1998,52(12):899-907
75 Wheeler JG,Bogie ML,Shema SJ.Impact of dietary yogurt on immune function.American Journal of Medical Science,1997,313(2):120-123
76 Water J,Keen C and Gershwin M.The influence of chronic yogurt consumption on immunity. Journal of Nutrition, 1999,129:1492-1498
77 Schiffrin EJ,Rochat F and Link-Amster H.Immunomodulation of Human Blood Cells Following the Ingestion of Lactic Acid Bacteria.Journal of Dairy Science,1995,78:491-497
78 Takahashi T,Oka T,Iwana H,et al.Immune Response of Mice to Orally Administered Lactic Acid bacteria.Bioscience Biotechnology and Biochemistry,1993,57(9):1557-1560
79范志红,宋锦萍,汪涛,等.饲喂酸奶不同时间对小鼠某些免疫功能指标的影响.中国乳品工业,2004,32(4):10-13
80 Donnet-Hughes A,Rochat F,Serrant P,et al.Modlation of nonspecific mechanisms of defense by Lactic acid bacteria:Efeective Dose.Journal of Dairy Science,1999,82:863-869
81 Perdigon GE,Vintini S,Alvarez M,et al.Study of the possible mechanisms involved in the mucosal immune system activation by lactic acid bacteria.Journal of Dairy Science,1999,82:1108-1114
82 Von der Weid T,Donnet-Hghes A,Blum S,et al.Scientific thoroughness of human studies showing immune-stimulating properties of yogurt.American Journal of Clinical Nutrition,2001,73(1):133-134
83 Fukui M,Fujino T, Tsutsui K,et al. The tumor-preventing effect of amixture of several lactic acid bacteria on 1,2-dimethylhydrazine-induced colon carcinogenesis in mice. Oncol Rep, 2001,8(5):1073-1078
84 Balansky R, Gyosheva B, Ganchev G, et al. Inhibitory effects of freezedried milk fermented by selected Lactobacillus bulgaricus strains on carcinogenesis induced by
1,2-dimethylhydrazine in rats and by diethylnitrosamine in hamsters. Cancer Lett, 1999,147(1-2):125-137
85 Femia AP, Luceri C, Dolara P, et al. Antitumorigenic activity of the prebiotic inulinenriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane induced colon carcinogenesis in rats. Carcinogenesis, 2002,23(11):1953-1960
86 Korshunov VM, Kafarskaia LI, Bagirova MSh,et al. The effect of SolcoTrichovac on the vaginal microflora of patients with a papillomavirus IFNection associatedwith a cervical intraepithelial neoplasm. ZhMikrobiol Epidemiol Immunobiol, 1994,5:13-17
87 Biffi A, Coradini D, Larsen R,et al. Antiproliferative effect of fermented milk on the growth of a human breast cancer cell line. Nutr Cancer,1997,28(1):93-99
88 Zabala A, Martin MR,Haza AI, et al. Anti-proliferative effect of tow lactic acid bacteria strains of human origin on the growth of a myeloma cell line.Lett Appl Microbiol, 2001,32(4):287-292.
89 Ohashi Y,Nakai S, Tsukamoto T,et al. Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Urol Int, 2002,68(4):273-280
90 Budagov RS, U1’ianova LP, Chureeva LN, et al. Efficacy of a preparation based on Lactobacillus acidophilus for protection from myelotoxic effects of ionizing radiation and antineoplastic cytostatics. Eksp Klin Farmakol, 2002,65(2):59-63
91 Seow SW, Rahmat JN, Mohamed AA, et al. Lactobacillus species is more cytotoxic to human bladder cancer cells than Mycobacterium Bovis(bacillus Calmette-Guerin).J Urol, 2002, 168(5): 2236-2239
92 Hamilton Miller JM. The role of probiotics in the treatment and prevention of helicobacter pylori IFNection. Int JAntimicrobAgents, 2003,22(4):360-366
93 Bauer G.Lactobacilli-mediated control of vaginal cancer through specific reactive oxygen species interaction. MedHypotheses, 2001,57(2):252-257
94 Kato I, Tanaka K, Yokokura T. Lactic acid bacterium potently induces the production of interleukin-12 and interferon-γby mouse splenocytes.Int J Immunophamacol, 1999,21(2):121-131.
95 Takagi A,Matsuzaki T, Sato M, et al. Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microor granism. Carcinogenesis,2001,22(4):599-605
96 Murosaki S, Muroyama K, Yamamoto Y, et al. Antitumor effect of heat-killedLactobacillus plantarumL-137 through restoration of impaired interleukin-12 production in tumor-bearing mice, Cancer Immunol Immunother, 2000,49(3):157-164
97 Takahashi T, Kushiro A, Nomoto K, et al. Antitumor effects of the intravesical instillation of heat killed cell of the Lactobacillus casei strain Shirota on the murine orthotopic bladder tumor MBT-2. J Urol, 2001,166(6):2506-2511
98 Chen T, Isomaki P, Rimpilainen M, et al. Human cytokine responses induced by gram-positive cell walls of normal intestinal microbiota. Clin Exp Immunol,1999,118(2):261-267
99 Kitazawa H, Watanabe H, Shimosato T, et al. Immunostimulatory oligonucleotide, CpG-like motif exists in Lactobacillus delbrueckii ssp.bulgaricus NIAI B6. Int J Food Microbiol, 2003,85(1-2):11-21
100 Lammers KM,Brigidi P, Vitali B, et al. Immunomodulatory effects of probiotic bacteria DNA: IL-1 and IL-10 response in human peripheral blood mononuclear cells. FEMS Immunol MedMicrobiol, 2003,38(2):165-172
101 Tejada Simon MV, Pestka JJ. ProIFNlammatory cytokine and nitric oxide induction in murine macrophages by cell wall and cytoplasmic extracts of lactic acid bacteria. J Food Prot, 1999,62(12)1435-1444
102 Heui DongP, ChangHo R. Antimutagenic activity of lactobacillus plantarum KLAB21 isolated from Kimchi Korean fermented vegetables.Biotechnol Lett, 2001,23(19):1583-1589
103 Yazawa K, Fujimori M, Amano J, et al. Bifidobacterium longum as adelivery systemfor cancergene therapy: selective localization and growth in hypoxic tumors. Cancer Gene Ther, 2000,7(2):269-274
104 Yazawa K, Fujimori M, Nakamura T, et al. Bifidobacterium longum as a delivery systemfor cancergene therapy of chemically induced ratmammmary tumors.Breast Cancer ResTreat, 2001,66(2):165-170
105 Thomberry NA,Lazebink Y.Caspases:enemieswithin[J]·Science,1998,281(5381):1312-1316
106王立生,朱惠明,潘令嘉,等.双歧杆菌对实验性大肠癌调亡促进基因表达的影响[J].中国微生态学杂志,2001,13(4):206-207
107王立生,潘令嘉,陈宏,等.双歧杆菌对实验性大肠癌bc1-2及bax基因表达的影响[J].中国癌症杂志,1998,8(3):253-256
108王立生,朱惠明,潘令嘉,等.双歧杆菌对实验性大肠癌NF-kB和IkBa的影响[J].中国病理生理杂志,2003,19(8):1062-1064
109康白主编.微生物学原理:免疫微生态学[M].大连:大连出版社,2002,76-88
110 Sakai M. Current research status of fish immunostimulants[J].Aquaculture, 1999,172:63-92
111康白.双歧杆菌[M].大连:大连海事大学出版社,1998,1-2
112孟和毕力格,乌日娜,王立平,杨续金,徐杰,董莹,孙志宏,张和平.不同地区酸马奶中乳杆菌的分离及其生物学特性的研究,中国乳品工业,2004,32(11)6-11
113乌日娜,张和平,孟和毕力格.酸马奶中乳杆菌Lb.casei.Zhang和ZL12-1的16S rDNA基因序列及聚类分析,中国乳品工业,2005,33(6)4-9
114张和平,孟和毕力格,王俊国,孙天松,徐杰,王立平,云月英,乌日娜.分离自内蒙古传统发酵酸马奶(Koumiss)中L.casei Zhang潜在益生特性的研究,中国乳品工业,2005,34(4)6-11
115 Simpson MA, Gozzo J J, Spectrophotometric determination of lymphocyte mediated sheep red blood cell hemolysis in vitro.JImmunol Methods,1978,21:159
116顾瑞霞,伊明.乳酸菌抗肿瘤特性的研究进展.中国微生态杂志,1999,11(4):253
117程波财,魏华.乳酸菌与肠粘膜免疫.中国微生态杂志,2001,13(5):302
118张洪泉,顾瑞霞,许爱华,等.五株活菌型乳酸对荷瘤小鼠的免疫调节作用.药物生物技术,1996,3(2):101
119清水精一.乳酸菌肠内フロフと健康はツ酵乳"マサイの战士"の开发と有效性にフ~て[ J].食品工业, 200(2): 40.
120骆承痒.乳与乳制品工艺学.北京:农业出版社,1992,236
121小崎道雄.日本食品工业学会志,1991,38,651
122 Ohara I.Jpn J.Dairy and Food science,1992,41(2),A-87
123何明清.动物微生态学[M].北京:中国农业出版社,1994
124杨景云.医用微生态学[M].北京:中国医药科技出版社,1997
125 Leer R J.Genetic analysis of a ciocin B,anovel bacterioncin produced by Lactobacillus acidophilus[J].Microbiology,1995,141:1 629-1 635
126郑健仙·功能性食品(第三卷)·北京:中国轻工业出版社, 1999
127周俭·保健食品设计原理及其应用·北京:中国轻工业出版社, 1998
128周勇·补益药药理研究方法[A]·见陈奇主编·中药药理研究方法学[C]·北京:人民卫生出版社,1993:172-173
129赖新峰,王立生,潘令嘉,等·双歧杆菌对裸鼠腹腔巨噬细胞激活作用的初步研究[J]·中国微生态学杂志,1999,1(6):336-337
130汪谦.现代医学实验方法[M].北京:人民卫生出版社,1997:690-691
131 GIL D,GARCIA L F,ROJAS M.Modulation of macrophage apoptosis by antimy-cobacterial theraphy:physiological role of apoptosis in the control of Myco-bacterium tuberculosis[J].Infect Immun,2004,65(2):1 886
132 Kobayshi M, Fitz L, Ryan M. Identification and purification on atural killer cell stimulatory fator (NKSF), a cytokine witmultiple biological effects on human lymphocytes〔J〕. J Exp Med 1989, 170: 827-845
133 Tazaki T, Minoguchi K, Yokoe T, et a.l Allergen rush immunotherapy increases interleukin ( IL)-12 production and IL-12 receptor beta2 chain expression in patientswith allergic asthma. Cell Immuno,l 2004, 228: 20-26
134 Brunda MJ,Luistro L,Warrier RR,et al.Antitumor and antimetastatic activity of interkeukin-12 against murine tumors.J Exp Med,1993,46:5276-5281
135 Dinarello C A. Proinflammatory cytokines. Chest. 2000, 118: 503-508
136 Majamaa.H, Isolauri.E, Saxelin.M, Vesikari.T. Lactic acid bacteria in the treatment of acute rotavirus gastroenteritis. J.Pediatr.Gastroenterol.Nutr. 1995;20:333-338
137 Chihara J. Stress and immunoallergy〔J〕. Rinsho Byori,1998,46(6):587
138 Prete DG,Magy E,Romagnani S. Human Th1and Th2cell:Functional properties,mechanism of regulation and role in disease〔J〕. Lab Investig,1994,70:299
139 Perdigon G,Nader De Macios M,Ak,arez S,et a1.Effect of perorally administered lactobacilli on macrophage activation in mice.Infection and lmnmnity 1986,53:404-410
140 Perdigon G,Nader de Macias ME Alvarez S,et a1.Enhancement of jmmune response in mice fedⅥithStreptococcus thermophilus and Lactobacillus acidophilus Journal of Dairy.Science 1 987,70:9 1 9-926
141 Hatcher GE and Lambrecht RS.Augmentation of microphage phagocytic activity b3, cell—free extracts of selected lactic acid—producing bacteria.Journal Of Dairy Science 1 993,76:2485—2492
142 Marin ML,Tejada—Simon MV,and Lee JH.Stimulation of cytokine production in clonal macrophage and T—ceil models by Streptococcus thermophilus:Comparison with Bifidobac—teriuln sp.and Lactobacillus bulgaricus.Journal of Food Protection 1 998,6 1(7):859-864
143 Marin ML Tejada—Simon MV Murtha J,et a1.Effects of Lactobacillus spp.on cytokine production by raw 264 7macrophage and EL一4 thymoma cell lines Journal ol’FoodProtection,l997 60(I1):l 364-l370
144 Muller-Alouf H,AloufJ,Gerlach D.et a1.Comparatk,e study of cytokine release by human peripheral blood mononuclcar cells stimulated with Streptococcus pyogenes superantigeic erythrogenic toxins , heat—killed Streptococci , and lipopolys—accharide.Infection and Immunity,l 998,62(1 1):49 1 5-492 1
145 Tejada—Simon MV,Ustunol Z and Pestka JJ.Ex vivo effects of lactobacilli,streptococci,and Bifidobacteria on cytokine and nitric oxide production in a murine mode1. Journal of Food Protection,1 999,62(2):l 62-1 69
146 De Simone C and Vesely R. Enhancement of hlllnune response of murine Peyer’s patches by a diet supplementedⅥrith yogurt . Immunophan11acology and In1mLmotoxic0logy l987.9(11):87-l00
147 Trapp CL,Chang CC,Halpern GM,et al The influence of chronic yogurt consumptionon populations ofyoung and elderl3,adults.1ntemational Journal of lmmunophannacology, 1 993,9:53-64
148 Matsuzaki T,Yamazaki R Hashimoto S,ct al Antidiabetic effects of an ordl administration of Lactobacillus case in a non—insulin—dependent diabetes roellitus (NIDDM) model using KK—A super(y) mice Endocrine Journa1.1 997.44 (3):357-365
149 Matsuzaki T,Yamazaki R and Hashimoto S.The effect oforal feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice.Journal of Dairy Science,1998 81(1):48-53
150 Muscettola M,Massai L,Tanganelli C.et al Efects of Lactobacilli on interferon production in young and aged mice.Annals New York Academy of Sciences . 1 994.7 l 7:227-232
151 Chen T,lsomaki P,Rimpi lainen M,et al Human cytokine responses induced by gram—positive cell walls of normal intestinal microbiota.C linical and Experi mental lmmuno.1ogy,1999,1 18(2):261-267
152 Tejada—Simon MV and Pestka JJ Proinflammatorv cvtokil1e and nitric oxide induction in murine macrophages b3r cell wall and c3,toplasmic extracts of lactic acid bacteria Journal of Food Protection,1999,62(121:1435-1444
153 SHIDA KK,MAKINO A,MORISHITA K,et al.Lactobacillus casei inhibits antigen induced IgE secretion through regulation of cytokine production in murine splenocyte cultures[J].Int Arch Allergy Immunol,1998
154 LIMBK,MAHENDRANR,LEE YK,et al.Chemopreventive effect of Lactobacillus rhamnosus on growth of a subcutaneously implanted bladder caner cell line in the mouse[J].Jpn J Cancer Res,2002,93(1):36-41
155余保平,王伟岸.消化系疾病免疫学[M].北京:科学出版社,2000. 45-50
156赖新峰,王立生,潘令嘉,等.双歧杆菌对裸鼠腹腔巨噬细胞激活作用的初步研究[J].中国微生态学杂志,1999,1(6):336-337
157 Mosmann T R,S Sed.The expanding universeof T-cell subsets: Th1,Th2 and more[J].Immunol.Today,1996,17:138-146
158 Prete DG,Magy E,Romagnani S.Human Th1 and Th2 cell:Functional properties,mechanism of regulation and role in disease[J].Lab Investing,1994,70:299
159 Smith KA. Lowest dose interleukin-2 immunotherapy.Blood, 1993; 81∶1414
160 Chihara J.Stress and immunoallergy[J].Rinsho Byori,1998,46(6):587
161 Waldmann TA. The interleukin-2 receptor. J Biol Chem,1991; 266∶2681
162 Romagnani,S. The Th1/Th2 paradigm. Immunol Today.1997,18:263-266
163张宝元,马晓红,刘霞,等.双歧杆菌及其WPG对S180荷瘤鼠免疫调节和抑制作用的研究[J].中国微生态学杂志,2001,13(1):8-10
164魏小龙,茹祥斌,王青定,等.用竞争性RT-PCR方法定量检测p53基因的表达[J].军事医学科学院院刊,1999, 23(2):107
165 Kruis W.Review article:antibiotics and probiotics in inflammatory bowel disease[J]·Aliment Pharmacol Ther,2004,20(Supp14):75-78
166 Sartor RB.Therapeutic manipulation of the enteric microflora in inflammatory boweldiseases; antibiotics, probiotics, andprebiotics[J].Gastroenterol,2004,126:1620-1633
167 PollardM, SharonN. Response of the peyer’s in germ freemice to angyenic stimulation[J]. Infect Immune, 1970, 2(4): 96-100
168 Matsunaga K, Morita I, Oguchi Yet al·The effect of a biological response modifier, PSK, on the intestinal immune system in tumor bearing mice[J].Anticance Res,1987; 7(3 Pt B):509
169 Nakasaki H, TajimaT, MitomiTet al·Countermeasuresfor hypofunction of gut associated lymphoidtissue during TPN inrats[J].Nippon-Shokakibyo-Gakkai-Zasshi,1996; 93(11):806
170王立生,潘令嘉,施理,等.双岐杆菌对裸鼠腹腔巨嗜细胞产生IL-1、IL-6、IL-12的影响[J].中华微生物学和免疫学杂志,1998,18(5)∶373
171 Hart A L, Lammers K, Brigidi P et al. Modulation of human dendritic cell phenotype and function勿probiotic bacteria. Gut. 2004, 53: 1602-1609
172 Vinderola QMartar C, Perdigon G Role of intestinal epithelial cells in immune effects mediated by gram-positive probiotic bacteria: involvment of Toll-like receptor. Clin Diagn Lab Immunol. 2005, 9: 1075-1084
173 Menard S, Candalh C, Bambou J C et al. Lactic acid bacteria secrete metabolites retaining anti-inflammatory properties after intestinal transport. Gut, 2004, 53:821-828
174 FUKATSU K,SAKAMOTO S,HARA E,et al.Gut ischemia reperfusion affects gut macosal immunity:a possible mechanism for infectious complications after severe surgical insults[J].Crit care Med,2006,34(1):182-187
175 SPAHN TW,KUCHARZIK T.Modulating the intestinal immune system:the role of lymphotoxin and GALT organs[J].Gut,2004,53:456-465
176王涛,黎沾良,王亚平.全肠外营养对肠免疫功能影响的研究.中华外科杂志,1996,34(5)307-310
177周正任.浅谈黏膜免疫机制[J].中国微生态学杂志, 2000,12(16): 311-312
178 Salminen S, IsolauriE, SalminenE. Clinicaluse ofprobiotics for stabilizing the gutmucosalbarrier: successful strains and future challenges[J]. Antonie van Leeuwenhoek,1996, 99(2):347-358
179 FullerR, Perdigon G. Probiotics 3: Immunodulation by the gut microflora and probiotics[M ]. Netherlands: Kluwer Academic Publisher, 2000. 213-233
180 Salminen S,Bouley,C Boutron-Ruault MCet al.Functional food science and gastrointestinal physiology and function[J].Bri J Nutri,1998,80(1):147-171
181祁保民,高齐瑜.动物粘膜免疫系统[J].中国兽医杂志,1998,24(4):55-57
182 TakahashiM, Iwata S, YamazakiN,etal.Phagocytosisof the lactic acid bacteria byM cells in the rabbitPeyer’sPatchs[J]. Clin ElectronMicrosc, 1991, 24(2) : 5-6
183 FamularoG, MorettiS, Marcellin,ietal. Stimulation of immunity by probiotics[M]. London: Chapman andHil,l 1997. 133-161
184 Garriga M,Pascual M.Selection of lactobacilli for chicken probiotic adjuncts[J].J Appl Microbiol,1998,84(1):125~132
185杨洁彬,郭兴华,张篪,等.乳酸菌—生物学基础及应用.北京:中国轻工业出版社,1996. 179～180,246～249
186胡东良.乳酸菌的抗肿瘤、抗变异原及免疫增强作用.中国乳品工业,1997,25(6):12～
14
187 Yasui H,Shida K,Matsuzaki T,et al . Immunomodulatory function of lactic acid bacteria. Antonie van Leeuwenhoek 1999,76:383～389
188 Niedzielin K, Kordecki H, Birkenfeld B. A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome.Eur J Gastroenterol Hepatol. 2001,13(10):1143-7
189 Ohashi Y,Nakai S, Tsukamoto T,et al. Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Urol Int, 2002,68(4):273-280
190 Fukui M,Fujino T, Tsutsui K,et al. The tumor-preventing effect of amixture of several lactic acid bacteria on 1,2-dimethylhydrazine-induced colon carcinogenesis in mice. Oncol Rep, 2001,8(5):1073-1078
191 Balansky R, Gyosheva B, Ganchev G, et al. Inhibitory effects of freeze-dried milk fermented by selected Lactobacillus bulgaricus strains on car-cinogenesis induced by 1,2-dimethylhydrazine in rats and by diethylni trosamine in hamsters. Cancer Lett, 1999,147(1-2):125-137
192 Femia AP, Luceri C, Dolara P, et al. Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probioticsLactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane induced colon carcinogenesis in rats. Carcinogenesis, 2002,23(11):1953-1960
193 Budagov RS, U1’ianova LP, Chureeva LN, et al. Efficacy of a preparation based onLactobacillus acidophilus for protection from myelotoxic effects of ionizing radiation and antineoplastic cytostatics. Eksp Klin Far-makol, 2002,65(2):59-63.
194 Nicholson DW, Thornberry NA. Apoptosis: Life and death decisions [J]. Science, 2003, 299(6504): 214-215
195 RESTA-LENERTS, BARRE TTKE. Live probiotics protectin testina lepithelial cells from the effects of infection with entero in vasive Escherichiacoli(EIEC)[J].Gut,2003,52:988-997
196康白.新抗微生物战略[C]∥湖南省首届微生态学与第三届医院感染学术会会议论文集,1988:15-31
197 GRONL UND MM,ARVIL OMMIH ,KER OP,etal.Importance of interstinal colonization in the maturation of humoral immunityin earlyinfancy :aprospective follow-up study of healthy in fantsaged0-6months[J].Archives of Diseasein Childhood,2000,83:186-192
198陈文学,史俊华.双歧杆菌的研究进展[J].中国微生态学杂志,2000(12):298-300
199 Yuya Y, Manabu K, Daishiro I, et al. Involvement of doxorubicin-induced Fas expression in the antitumor effect of doxorubicin on Lewis lung carcinoma in vivo[J]. International Immunopharma cology, 2005,5: 281-288
200 Kato I, Tanaka K, Yokokura T. Lactic acid bacterium potently induces the production of interleukin-12 and interferon-γby mouse splenocytes.Int J Immunophamacol, 1999,21(2):121-131
201 Takagi A,Matsuzaki T, Sato M, et al. Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microor granism. Carcinogenesis,2001,22(4):599-605
202陈慰峰.医学免疫学(第三版)[M].北京:人民卫生出版社,2001:81-84
203 Kuboya T, McNamaraDM, Wang JJ,etal. Effects of tumornecrosis factors gene polymorphism on patientswith congestive heart failure. Circulation. 1998, 97(25): 2499
204 Browning J, Ribolini A. Study on the differing effects of tumor necrosis factor and lymphotoxin on the growth of several human tumor lines. J Immunol, 1992,77:411
205 Seow SW, Rahmat JN, Mohamed AA, et al. Lactobacillus species is more cytotoxic to human bladder cancer cells than Mycobacterium Bovis(bacillus Calmette-Guerin).J Urol, 2002,168(5):2236-2239
206 Martin S T,Green D R·Apoptosis and cancer: the failure of control son cell death and cell survival·CRC Cit Rev Oncol Hematol,1995,18(2):137-153
207 Rosse T, Olivier R, Monney L,et al. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c [J]. Nature, 1998, 391(6666): 496-499
208 Guo B, Zhai D, Cabezas E,et al. Humanin peptide suppresses apoptosis by interferingwith Bax activation [J]. Nature, 2003,423(6938): 456-461
209崔玉芳,杨红,高亚兵,等.辐射诱发小鼠淋巴结细胞凋亡特征和意义的研究.中华放射医学与防护杂志,2001,21:6365
210 Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death [J]. Cell, 1993, 74(4): 609-619
211 Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death·Cell, 1993,74(4):609-619
212 Yi X, Yin XM, Dong Z·Inhibition of Bid-induced apoptosis by Bcl-2·tBid insertion,Bax translocation,and Bax/Bak oligomerization suppressed·J Biol Chem, 2003, 278(19):16992-16999
213 Bareton GB, Piebol dJ,Christot foris G,etal. ApoPtosis and immunohis toehemieal Bel2ex ressionin colore ctaladenomas andeareinomas,aspectso fearino gensisand Prognostic significanee[J].Caneer,1996;77(2):255-264
214 Hockenbe DM.Bel一2ineancer,develoPmentand aPOPtosis[J].CellSei,1994,18(s):51-59
215 Huang Y,RS ,Reed JC,etal. Estronin ereasesintra cellular P26 to PZI BaX ratosan dinhibitstaxo lindueed aPoPtosis of human breasteaneer MCF7ceells[J].BreastCancer ResTreat,1997:42(l):73-81
216 Reed J C.Bcl-2 and the regulation of programmed cell death〔J〕. J CellBio,l 1993,
75(2): 241
217 MiyashitaT,Reed JC.Bcl-2 oncoprotein block chemotherapy induced apoptosis in a human leukemia cell line〔J〕. Blood,1993, 81(1): 151
218 Krajewski S, Krajewska M, Shabaik A, et a.l Immunohisto chemicaldetermination of in vivo distribution ofBax, a dominant inhibitor ofBcl-2〔J〕.Am J Patho,l 1994, 145: 1323
219李勇,潘立峰.化疗诱导人胃癌细胞凋亡及Bcl-2、Bax基因蛋白表达变化的研究〔J〕.河北医科大学学报, 2001,22(3): 163
220 SultanaH,Kigawa J,KanamoriY. Chemosensitivity and p53-Bax pathway-mediated apoptosis in patientswith uterine cervical cancer〔J〕.Ann Onco,l 2003, 14(2): 214.
221 Krest I, Keusgen M. Quality of Herbal Remedies from Allium sativum: Differences between Alliinase from Garlic Powder and Fresh Garlic[J]. Planta Medica, 1999,65:1339-1343
222 Siegers CP, Stefffen B, Robke A, et al. The effects of garlic preparations against human tumor cell proliferation[J]. Phytomedicine, 1999,6:7-11.
223 Hirsch K, Danilenko M, Giat J, et al. Effect of purified allicin,the major ingredient of freshly crushed garlic, on cancer cell proliferation[J]. Nutr Cancer, 2000,38:245-254
224 Takeda K, Smyth M J, Cretney E,et al. Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development [J].J Exp Med, 2002, 195(2): 161-169.
225 Yu C L, Ye T X, Lu D Y,et al.Modern Medical Immunology(现代医学免疫学) [M]. Shanghai: Shanghai University of Medical Science Publishing House, 1998
226 Ma Y, Ma Y Z, Zhang J Y,et al. Regulatory effects of polysaccharide Fb from Huangmo on immunological function in mice [J].J Jilin Univ:Med Ed(吉林大学学报:医学版),2005, 31(5): 692-695
227 asegawa H, Suzuki R, Nagaoka T,et al. Prevention of growth and metastasis of murine melanorr a through enbanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatrio [J].Biol Pharm Bull, 2002, 25(7): 861-866
228 Tsai Y J, Chen I L, Horng L Y,et al. Induction of differentiation in rat C6 glioma cells with Saiko saponins [J].Phytother Res, 2002, 16(2): 117-121
229 Bruck I,O DonnellM. The ring-type polymerase sliding clamp family[J].Genome Bio,l 2001, 2(1):REVIEWS3001
230 NishitaniH,Lygerou Z.Control ofDNA replication licensing in a cell cycle[J].Genes to cells, 2002, 7(6): 523-534
231 StevauxO,Dyson NJ. A revised picture of the E2F transcript tionalnetwork and RB function[J].CurrOpin cellBio, 2002, 14(6): 684-691
232 TsurimotoT. PCNA binding proteins[J]. FrontBiocsc,i 1999,4:D849-858
233 Habib MR, Joel AH, Qing F. Modulation of apoptosis by nitric oxide:implications in myocardial ischemia and heart failure[J].Pharmacology&Therapeutics, 2005, 106: 147-162
234 Castellon E, Clementi M, Hitschfeld C, Sanchez C, Benitez D, Saenz L, et al.Effect of leuprolide and cetrorelix on cell growth, apoptosis, and GnRH receptor expression in primary cell cultures from human prostate carcinoma [J].Cancer Invest. 2006, 24(3):261-268
235 Fan HT, Xiong XY, Cao W, Gao ZB, Li XQ, Jia M, et al. Effects of proliferation inhibition and apoptosis of resveratrol trinicotinate on HepG2 cells and its mechanism[J].Chin J Clin pharmacol Then 2006, 11 (5 ):540-544
236 Zhan HX,Zhong CG,Xu SQ,Li HW. Relationships of hexavalent chromium( VI)-induced apoptosis,oxidadve damage and expressions of p53 and caspase3 in L-02 hepatocytes [J].Chin J Pharmacol Toxicol, 2006, 20 (2):144-151
237 Zhan J, Yang J, Tang HB. Inhibitory effect of isoliquiritigenin on proliferation of human cervical cancer cells in vitro and in vivo [J].Chin J Pharmacol Toxicoi, 2005,19(6):436-442
238唐忠志,付立波,唐瑛.丹参酮ⅡA抑制人肝癌细胞的生长及诱导其凋亡的实验研究[J] .第三军医大学学报,2003,25(9):774-776
239 Naryzhny SN,Desouza LV,Siu KW,et al.Characterization of the human proliferating cell nuclear antigen physico-chemical properties:aspects of double trimer stability[J].Biochem Cell Biol,2006,84(5):669-676
240岳辉,张宁,冯新莉,等.胰腺癌组织中p57kip2、Cyclin E和PCNA表达与临床病理因素的关系[J].癌症,2003,22(7):705-709
241 Oketani M,Kohara K,Tuvdendorj D,et a1.Inhibition by arsenictrioxide of human hepatoma cell growth[J].Cancer Lett,2002,183(2):147-153
242 Blain SW,Scher HI,Cordon-Cardo C,et a1.p27 as a target for cancer therapeutics[J].Cancer Cell,2003,3(2):111-115
243 Ganoth D,Bornstein G,Ko TK,et al.The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27[J].Nat Cell Biol,2001,3(3):321-324
244 Yokoi S,Yasui K,Saito-Ohara F,et al.A novel target gene,SKP2,within the 5p13 amplicon that is frequently detected in small cell lung cancers[J].Am J Pathol,2002,161(1):207-216
245 Kuznetosv G, Towle MJ, Cheng H, et al. Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389[J].Cancer Res,2004,64(16):5760-5766
246云月英,王立平,陈永福,孟和毕力格,张和平.喂饲Lactobacillus casei Zhang对大鼠体内脂质代谢的影响.微生物学通报, 2006. 33(3) : 60-64
247张和平,张七斤,孟和毕力格,任贵强. L.casei zhang对小鼠T淋巴细胞亚群及血清IgG和肠黏膜SigA的影响.中国乳品工业, 2006. 34(10): 4-8
248托娅,苏雅勒玛,张和平.乳杆菌L.casei zhang对小鼠血清中细胞因子水平的影响.食品科学, 2006, 27(11): 488-491
249王俊国,孟和毕力格,张和平*,陈永福,包秋华.干酪乳杆菌Zhang对大鼠抗氧化能力的影响[J].营养学报,2008,30(1):1-6
2黄秀梨主编.微生物学(第二版).北京:高等教育出版社,2003
3郭本恒主编.益生菌.北京:化学工业出版社,2004
4凌代文.乳酸细菌分类鉴定及实验方法.北京:中国轻工业出版社,1999
5孟昭赫.乳酸菌与人类健康.北京:人民卫生出版社,1993
6郭兴华.益生菌基础与应用.北京:北京科学技术出版社,2002
7杨汝德,林勉,陈惠音.益生素及其应用.中国乳品工业,2000,28(1),29-31
8 Gionchetti P, Rizzello F, Venturi A, etal. Oralbacterio the rapyas mainte nancetrea tmentinp at ients with chronic pouchhitis:Adou-ble-blind,placebo-controlledtrial.Gastroenterology,2000,119:1512-1517.
9张自德,冯燕.蜡样芽抱杆菌活菌制剂治疗婴幼儿及成人腹泻60例临床观察.中国微生态学杂志,1999,6(3):177-180
10蓝景刚,胡宏.双歧杆菌及其表面分子的免疫增强作用.中国微生态学杂志,1999,11(3):129-131
11王树山,杨松,邓莉,等.微生态制剂“妈咪爱”治疗婴幼儿轮状病毒肠炎的临床研究.中国微生态学杂志,1996,8(3):31-33
12赖新峰,王立生,潘令嘉,等.双歧杆菌对裸鼠的腹腔巨噬细胞激活作用的初步观察.中国微生态学杂志,1999,11(6):336-337
13 Clausen M.R. ,H.,Tvede,M.,and Mortensen, P.B.(1991). Colonic Fer-mentationto Short-chain Fatty Acidsis decrease dinantibiotic -asso- ciateddia rrhea.Gastroenterology 101,1497-1504
14 Survival of Lactob qacillusaci do philusinaspray- dryingprocess Es-pina & Packard.J. Food protect 42: 149-152
15何国庆,孔青,等.益生菌的功效与潜在危害[J].食品科技,2004(1):12-15
16李琴,张世春,等.益生菌营养及保健作用[J].食品研究与开发,2004,25(2):106-109
17 Serum cholesteroland bowelflorain thenew born Harrison&peat.1975,Am J Clin.nutr,28:1351-1355
18杨维军,王华,等.益生菌的功效及其在食品中的应用[J].四川食品与发酵,2005(1):27-30
19 Pouwels.,P.H.Leer,R.J.Shaw.M,etal.Lactic acid bactria as antigen delivery vehickes for oral immunization purpose.Int.J.FoodTechnol41,1998:155-167
20董珂,刘晶晶,等.益生菌增强集体免疫和抗肿瘤作用的分子机制[J].中国微生态学杂,2005,17(1):79-81
21蒋寒青,康白.肠道生理性细菌粘附机制的研究进展.中国微生态学杂志,1995(1):48-49
22钟燕.益生菌与乳糖不耐受研究进展.国外医学卫生学分册,2003,30(2):101-105
23郑跃杰,潘令嘉,王立生,等.双歧杆菌粘附素的纯化.中华微生物和免疫学杂志,1999,19(3):1961
24苏世彦.双歧杆菌的分离、鉴定与驯化.江苏食品与发酵,1998(2):10-13
25田允波,葛长荣,张曦.益生素的研究和应用现状.兽药与饲料添加剂,1999,4(3):36-39
26张自德,冯燕.蜡样芽抱杆菌活菌制剂治疗婴幼儿及成人腹泻60例临床观察.中国微生态学杂志,1999,6(3):177-180
27 GILL HS,RUTHERFURD KJ,et al.Enhancement of natural and acquired immunity by Lactobacillus rhamnosus (HN001),Lactobacillus acidophilus (HN017) and Bifidobacterium lactis (HN019)[J].Br J Nutr.2000 Feb,83(2):167-176
28 HALLER D,SERRANT P,PERUISSEAU G,et al.IL-10 producing CD14low monocytes inhibit lymphocyte-dependent activation of intestinal epithelial cells by commensal bacteria[J].Microbiol Immunol,2002,46(3):195-205
29 CANGEMI de Gutierrez,RV,SANTOS de Araoz,ME NADER-MACIAS.Effect of intranasal administration of Lactobacillus fermentum on the respiratory tract of mice[J].Biol Pharm Bull,2000,23:973-978
30 CANGEMI de Gutierrez R,SANTOS V,NADER-MACIAS ME.Protective effect of intranasally inoculated Lactobacillus fermentum against Streptococcus pneumoniae challenge on the mouse respiratory tract[J].FEMS Immunol Med Microbiol,2001 ,31(3):187-195
31 MARIN ML,TEJADA-SIMON MV,LEE J H,et al.Stimulation of cytokine production in clonal macrophage and T-cell models by Streptococcus thermophilus:comparison with Bifidobacterium sp.and Lactobacillus bulgaricus[J].J Food Prot, 1998, 61: 859 -864
32 PELTO L,ISOLAURI E,LILIUS EM,et al.Probiotic bacteria down-regulate the milk-induced inflammatory response in milk- hypersensitive subjects but have an immunostimulatoryeffectin healthy subjects[J].Clin Exp Allergy,1998,28:1474-1479
33 TAKAGI AT,MATSUZAKI M,SATO K,et al.Enhancement of natural killer cytotoxicity delayedmurinecarcinogenesisbyaprobioticmicroorganism[J].Carcinogenesis,2001,22:599-605
34 HALLER D,SERRANT P,GRANATO D,et al.Activation of Human NK Cells by Staphylococci and Lactobacilli Requires Cell Contact-Dependent Costimulation by Autologous Monocytes[J].Clinical and Diagnostic Laboratory Immunology,2002,9(3):649-657
35 HANNE R.Lactobacilli Differentially Modulate Expression of Cytokines and Maturation Surface Markers in Murine Dendritic Cells [J]. The Journal of Immunology,2002,168:171-178.
36 SHIDA KK,MAKINO A,MORISHITA K,et al.Lactobacillus casei inhibits antigen-induced IgEsecretion through regulation of cytokine production in murine splenocyte cultures[J].Int Arch Allergy Immunol,1998.
37 LIM BK,MAHENDRAN R,LEE YK,et al.Chemopreventive effect of Lactobacillus rhamnosus on growth of a subcutaneously implanted bladder cancer cell line in the mouse[J].Jpn J Cancer Res,2002 ,93(1):36-41
38 De WAARD R,CAASSEN E,BOKKEN GC,et al.Enhanced Immunological Memory Responses to Listeria monocytogenes in Rodents, as Measured by Delayed-Type Hypersensitivity (DTH),Adoptive Transfer of DTH, and Protective Immunity, following Lactobacillus casei Shirota Ingestion Clinical and Diagnostic Laboratory Immunology, 2003,10(1):59-65
39 De Waard R, GARSSEN J,SNEL J,et al.Enhanced antigen-specific delayed-type hypersensitivity and immunoglobulin G2b responses after oral administration of viable Lactobacillus casei YIT9029 in Wistar and Brown Norway rats[J].Clin Diagn Lab Immunol,2001,8:762-767
40 HORI T,KIYOSHIMEA J,SHIDA K,et al.Augmentation of Cellular Immunity and Reduction of Influenza Virus Titer in Aged Mice Fed Lactobacillus casei Strain Shirota[J].Clinical and Diagnostic Laboratory Immunology,2002,9(1):105-108
41 POCHARD P,GOSSET P,et al.Lactic acid bacteria inhibit TH2 cytokine production by mononuclear cells from allergic patients [J].J Allergy Clin Immunol,2002 ,110(4):617-623.
42 PERDIGON G,ALVAREZ S,RACHID M,et al.Immune system stimulation by probiotics[J].J Dairy Sci,1995,78:1597-160
43 Blum S,Alvarze S and Haller D.Intestinal microflora and the interaction with immunocompetent cells.Antonie van Leeuwenhoek,1999,76:199-205
44王立生.双歧杆菌的免疫激活作用及其生物学意义.国外医学生理,病理科学与临床分册,1998,18(4):320-322
45 Lee J,Ametani A,Enomoto A,et al.Motoshima H:Ike F and Kaminogawa S.Screening for the immunopotentiatng activity of food microorganisms and enhancement of the immune response by Bifidobacterium adolescentis M101-4.Bioscience,Biotechnology and Biochemistry,1993,57:2127-2130.
46 Tejado-Simon MV,Lee JH,Ustunol Z,et al.Ingestion of yogurt containing Lactobacillus acidophilus and Bifidobacterium to potentiate immunoglobulin A response to choleratoxin in mice.Journal of Dairy Science.1999,82:649-660
47 Takahashi T,Oka T,Iwana H,et al.Immune Response of Mice to Orally Administcred LacticAcidbacteria. Bioscience. BiotechnologyandBiochemistry.1993,57(9):1557-1560
48 Marin ML,Lee JH,Murtha J,et al.Differential cytokine production in clonal macrophageand T cell lines cultured with Bifidobacterium sp.Journal of Dairy Science,1997,80:2713-2720
49 Perdigon G.Systemic augmentation of the immune response in mice by feeding ferment edmilk swith Lactobacillus casei and Lactobacillus acid ophilus.1988,Immunology 63:17-21
50 Maassen CB,Yamazaki R and Hashimoto S,et al.The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice.Journal of Dairy Science,1998,81(1):48-53.
51 Shida K,Makino K and Morishita A.Lactobacillus casei Inhibits Antigen-Induced IgE Secretion through Regulation of Cytokine Production in Murine Splenocyte Cultures.International Archives of Allergy and Immunology,1998.115(4):278-287
52 Matsuzaki T,Yamazaki R and Hashimoto S.The effect of oral feeding of Lactobacillus casei Shirota on immunoglobulin E production in mice.Joumal of Dairy Science.1998.81(1):48-53
53 Marin ML,Tejada-Simon MV,and Lee JH.Stimulation of cytokine production in clonal macrophage and T-cell models by Streptococcus thermophilus:Comparison with Bifidobacterium sp.and Lactobacillus bulgaricus Joumal of Food Protection,1998,61(7):859-864
54 Miettinen M,Matikainen S and Vuopio-Varkila J,et al.Lactobacillus and Streptococci Induce Interleukin-12(IL-12).IL-18,and Gamma Interferon Production in Human Peripheral Blood Mononuclear Cells.Infection and Immunity,1998,66(12):6058-6063
55 Perdigon G,Nader De Macios,M and Alvarez S,et al.Enhancement of immune response in mice fed with Streptococcus thermophilus and Lactobacillus acidophilus.Journal of Dairy Science, 1987, 70: 919-926
56 Zhan Y and Cheers C.Differential induction of macrophagederived cytokines by live and dead intracellular bacteria in vitro.Infection and Immunity,1995,63(2):720-723
57 Marin ML,Tejada-Simon MV,Murtha J,et al.Efeects of Lactobacillus spp on cytokine production byraw 264.7 macrophage and EL-4 thymoma cell lines.Journal of Food Protection, 1997, 60(11): 1364-1370
58 Perdigon G,Nader De Macios M,Alvarez S,et al.Efeect of perorally administered lactobacilli on macrophage activation in mice.Infection and Immunity,1986,53:404-410
59 Perdigon G,Nader De Macias ME,Alvarez S,et al.Enhancement of immune response in mice fed with Streptococcus thermophilus and Lactobacillus acidophilus.Journal of Dairy Science, 1987, 70: 919-926
60 Hatcher GE and Lambrecht RS.Augmentation of microphage phagocytic activity bycell-free extracts of selected lactic acid-producing bacteria.Journal of Dairy Science,1993,76:2485-2492
61 Muller-Alouf H,Alouf J,Gerlach D,et al.Comparative study of cytokine release by human peripheral blood mononuclear cells stimulated with Streptococcus pyogenes superantigeic erythrogenic toxins heat-killed Streptococci,and lipopolysaccharide.Infection and Immunity,1998,62(11):4915-4921
62 Tejada-Simon MV,Ustunol Z and Pestka JJ.Exvivo effects of lactobacilli,streptococci,and Bifidobacteria on cytokine and nitric oxide production in a murine model.Journal of Food Protection,1999,62(2):162-169
63 De Simone C and Vesely R.Enhancement of immune response of murine Peyer’s patches by a diet supplemented with yogurt.Immunopharrnacology and Immunotoxicology,1987,9(1):87-100
64 Trapp CL,Chang CC,Halpern GM,et al.The influence of chronic yogurt consumption on populations of young and elderly adults.Intemational Journal of Immunophannacology,1993,9:53-64.
65 Matsuzaki T,Yamazaki R,Hashimoto S,et al.Antidiabelic effects of an oral administration of Lactobacillus casei in a non-insulin-dependent diabetes mellitus (NIDDM) model using KK-A super(y) mice.Endocrine Journal,1997,44(3):357-365
66 Muscettola M,Massai L,Tanganelli C,et al.Effects of Lactobacilli on interferon production in young and aged mice.Annals New York Academy of Scienecs,1994,717:227-232
67 Chen T,Isomaki P,Rimpilainen M,et al.Human cytokine responses induced by gram-positive cell walls of normal intestinal microbiota.Clinical and Experimental Immunology,1999,118(2):261-267.
68 Tejada-Simon MV and Pestka JJ.Proinflammatory cytokine and nitric oxide induction in murine macrophages by cell wall and cytoplasmic extracts of lactic acid bacteria.Journal of Food Protection.1999,62(12):1435-1444
69 Perdigon G,Alvarez S,Rachid M,et al.Symposium:Probiotic bacteria for humans:clinical systems for evaluation of effectiveness.Journal of Dairy Science 1993,78:1597-1606
70 Popova P and Guencheva G.Lactobacillus Stimulating effect of deodan(an oral preparation from Lactobacillus bulgarcus“LB51”)on monocytes/macrophages and host resistance to experimental infections.International Journal of Immunopharmacology,1993,15:25-27
71 Morata de Ambrosini V,Gonzalez S,Perdigon G,et al.Immunostimulating Activity of Cell Walls from Lactic Acid Bacteria and Related Species.Food and AgriculturalImmunology.1998,10(2):183-191.
72 Tejada-Simon MV.Ustunol Z and Pestka JJ.Effects of Lactic acid bacteria ingestion of basal cytokine mRNA and immunoglobulin levels in mouse.Journal of Food Protection.1999,62(3):287-291.
73 Ha CL,Lee JH,Zhou HR,et al.Efeects of yogurt ingestion on mucosal and systemic cytokine gene expression in the mouse.Journal of Food Protection.1999,62(2):181-188
74 Spanhaak S,Havenaar R and Schaafsma G.The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans.European Journal of Clinical Nutrition,1998,52(12):899-907
75 Wheeler JG,Bogie ML,Shema SJ.Impact of dietary yogurt on immune function.American Journal of Medical Science,1997,313(2):120-123
76 Water J,Keen C and Gershwin M.The influence of chronic yogurt consumption on immunity. Journal of Nutrition, 1999,129:1492-1498
77 Schiffrin EJ,Rochat F and Link-Amster H.Immunomodulation of Human Blood Cells Following the Ingestion of Lactic Acid Bacteria.Journal of Dairy Science,1995,78:491-497
78 Takahashi T,Oka T,Iwana H,et al.Immune Response of Mice to Orally Administered Lactic Acid bacteria.Bioscience Biotechnology and Biochemistry,1993,57(9):1557-1560
79范志红,宋锦萍,汪涛,等.饲喂酸奶不同时间对小鼠某些免疫功能指标的影响.中国乳品工业,2004,32(4):10-13
80 Donnet-Hughes A,Rochat F,Serrant P,et al.Modlation of nonspecific mechanisms of defense by Lactic acid bacteria:Efeective Dose.Journal of Dairy Science,1999,82:863-869
81 Perdigon GE,Vintini S,Alvarez M,et al.Study of the possible mechanisms involved in the mucosal immune system activation by lactic acid bacteria.Journal of Dairy Science,1999,82:1108-1114
82 Von der Weid T,Donnet-Hghes A,Blum S,et al.Scientific thoroughness of human studies showing immune-stimulating properties of yogurt.American Journal of Clinical Nutrition,2001,73(1):133-134
83 Fukui M,Fujino T, Tsutsui K,et al. The tumor-preventing effect of amixture of several lactic acid bacteria on 1,2-dimethylhydrazine-induced colon carcinogenesis in mice. Oncol Rep, 2001,8(5):1073-1078
84 Balansky R, Gyosheva B, Ganchev G, et al. Inhibitory effects of freezedried milk fermented by selected Lactobacillus bulgaricus strains on carcinogenesis induced by
1,2-dimethylhydrazine in rats and by diethylnitrosamine in hamsters. Cancer Lett, 1999,147(1-2):125-137
85 Femia AP, Luceri C, Dolara P, et al. Antitumorigenic activity of the prebiotic inulinenriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane induced colon carcinogenesis in rats. Carcinogenesis, 2002,23(11):1953-1960
86 Korshunov VM, Kafarskaia LI, Bagirova MSh,et al. The effect of SolcoTrichovac on the vaginal microflora of patients with a papillomavirus IFNection associatedwith a cervical intraepithelial neoplasm. ZhMikrobiol Epidemiol Immunobiol, 1994,5:13-17
87 Biffi A, Coradini D, Larsen R,et al. Antiproliferative effect of fermented milk on the growth of a human breast cancer cell line. Nutr Cancer,1997,28(1):93-99
88 Zabala A, Martin MR,Haza AI, et al. Anti-proliferative effect of tow lactic acid bacteria strains of human origin on the growth of a myeloma cell line.Lett Appl Microbiol, 2001,32(4):287-292.
89 Ohashi Y,Nakai S, Tsukamoto T,et al. Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Urol Int, 2002,68(4):273-280
90 Budagov RS, U1’ianova LP, Chureeva LN, et al. Efficacy of a preparation based on Lactobacillus acidophilus for protection from myelotoxic effects of ionizing radiation and antineoplastic cytostatics. Eksp Klin Farmakol, 2002,65(2):59-63
91 Seow SW, Rahmat JN, Mohamed AA, et al. Lactobacillus species is more cytotoxic to human bladder cancer cells than Mycobacterium Bovis(bacillus Calmette-Guerin).J Urol, 2002, 168(5): 2236-2239
92 Hamilton Miller JM. The role of probiotics in the treatment and prevention of helicobacter pylori IFNection. Int JAntimicrobAgents, 2003,22(4):360-366
93 Bauer G.Lactobacilli-mediated control of vaginal cancer through specific reactive oxygen species interaction. MedHypotheses, 2001,57(2):252-257
94 Kato I, Tanaka K, Yokokura T. Lactic acid bacterium potently induces the production of interleukin-12 and interferon-γby mouse splenocytes.Int J Immunophamacol, 1999,21(2):121-131.
95 Takagi A,Matsuzaki T, Sato M, et al. Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microor granism. Carcinogenesis,2001,22(4):599-605
96 Murosaki S, Muroyama K, Yamamoto Y, et al. Antitumor effect of heat-killedLactobacillus plantarumL-137 through restoration of impaired interleukin-12 production in tumor-bearing mice, Cancer Immunol Immunother, 2000,49(3):157-164
97 Takahashi T, Kushiro A, Nomoto K, et al. Antitumor effects of the intravesical instillation of heat killed cell of the Lactobacillus casei strain Shirota on the murine orthotopic bladder tumor MBT-2. J Urol, 2001,166(6):2506-2511
98 Chen T, Isomaki P, Rimpilainen M, et al. Human cytokine responses induced by gram-positive cell walls of normal intestinal microbiota. Clin Exp Immunol,1999,118(2):261-267
99 Kitazawa H, Watanabe H, Shimosato T, et al. Immunostimulatory oligonucleotide, CpG-like motif exists in Lactobacillus delbrueckii ssp.bulgaricus NIAI B6. Int J Food Microbiol, 2003,85(1-2):11-21
100 Lammers KM,Brigidi P, Vitali B, et al. Immunomodulatory effects of probiotic bacteria DNA: IL-1 and IL-10 response in human peripheral blood mononuclear cells. FEMS Immunol MedMicrobiol, 2003,38(2):165-172
101 Tejada Simon MV, Pestka JJ. ProIFNlammatory cytokine and nitric oxide induction in murine macrophages by cell wall and cytoplasmic extracts of lactic acid bacteria. J Food Prot, 1999,62(12)1435-1444
102 Heui DongP, ChangHo R. Antimutagenic activity of lactobacillus plantarum KLAB21 isolated from Kimchi Korean fermented vegetables.Biotechnol Lett, 2001,23(19):1583-1589
103 Yazawa K, Fujimori M, Amano J, et al. Bifidobacterium longum as adelivery systemfor cancergene therapy: selective localization and growth in hypoxic tumors. Cancer Gene Ther, 2000,7(2):269-274
104 Yazawa K, Fujimori M, Nakamura T, et al. Bifidobacterium longum as a delivery systemfor cancergene therapy of chemically induced ratmammmary tumors.Breast Cancer ResTreat, 2001,66(2):165-170
105 Thomberry NA,Lazebink Y.Caspases:enemieswithin[J]·Science,1998,281(5381):1312-1316
106王立生,朱惠明,潘令嘉,等.双歧杆菌对实验性大肠癌调亡促进基因表达的影响[J].中国微生态学杂志,2001,13(4):206-207
107王立生,潘令嘉,陈宏,等.双歧杆菌对实验性大肠癌bc1-2及bax基因表达的影响[J].中国癌症杂志,1998,8(3):253-256
108王立生,朱惠明,潘令嘉,等.双歧杆菌对实验性大肠癌NF-kB和IkBa的影响[J].中国病理生理杂志,2003,19(8):1062-1064
109康白主编.微生物学原理:免疫微生态学[M].大连:大连出版社,2002,76-88
110 Sakai M. Current research status of fish immunostimulants[J].Aquaculture, 1999,172:63-92
111康白.双歧杆菌[M].大连:大连海事大学出版社,1998,1-2
112孟和毕力格,乌日娜,王立平,杨续金,徐杰,董莹,孙志宏,张和平.不同地区酸马奶中乳杆菌的分离及其生物学特性的研究,中国乳品工业,2004,32(11)6-11
113乌日娜,张和平,孟和毕力格.酸马奶中乳杆菌Lb.casei.Zhang和ZL12-1的16S rDNA基因序列及聚类分析,中国乳品工业,2005,33(6)4-9
114张和平,孟和毕力格,王俊国,孙天松,徐杰,王立平,云月英,乌日娜.分离自内蒙古传统发酵酸马奶(Koumiss)中L.casei Zhang潜在益生特性的研究,中国乳品工业,2005,34(4)6-11
115 Simpson MA, Gozzo J J, Spectrophotometric determination of lymphocyte mediated sheep red blood cell hemolysis in vitro.JImmunol Methods,1978,21:159
116顾瑞霞,伊明.乳酸菌抗肿瘤特性的研究进展.中国微生态杂志,1999,11(4):253
117程波财,魏华.乳酸菌与肠粘膜免疫.中国微生态杂志,2001,13(5):302
118张洪泉,顾瑞霞,许爱华,等.五株活菌型乳酸对荷瘤小鼠的免疫调节作用.药物生物技术,1996,3(2):101
119清水精一.乳酸菌肠内フロフと健康はツ酵乳"マサイの战士"の开发と有效性にフ~て[ J].食品工业, 200(2): 40.
120骆承痒.乳与乳制品工艺学.北京:农业出版社,1992,236
121小崎道雄.日本食品工业学会志,1991,38,651
122 Ohara I.Jpn J.Dairy and Food science,1992,41(2),A-87
123何明清.动物微生态学[M].北京:中国农业出版社,1994
124杨景云.医用微生态学[M].北京:中国医药科技出版社,1997
125 Leer R J.Genetic analysis of a ciocin B,anovel bacterioncin produced by Lactobacillus acidophilus[J].Microbiology,1995,141:1 629-1 635
126郑健仙·功能性食品(第三卷)·北京:中国轻工业出版社, 1999
127周俭·保健食品设计原理及其应用·北京:中国轻工业出版社, 1998
128周勇·补益药药理研究方法[A]·见陈奇主编·中药药理研究方法学[C]·北京:人民卫生出版社,1993:172-173
129赖新峰,王立生,潘令嘉,等·双歧杆菌对裸鼠腹腔巨噬细胞激活作用的初步研究[J]·中国微生态学杂志,1999,1(6):336-337
130汪谦.现代医学实验方法[M].北京:人民卫生出版社,1997:690-691
131 GIL D,GARCIA L F,ROJAS M.Modulation of macrophage apoptosis by antimy-cobacterial theraphy:physiological role of apoptosis in the control of Myco-bacterium tuberculosis[J].Infect Immun,2004,65(2):1 886
132 Kobayshi M, Fitz L, Ryan M. Identification and purification on atural killer cell stimulatory fator (NKSF), a cytokine witmultiple biological effects on human lymphocytes〔J〕. J Exp Med 1989, 170: 827-845
133 Tazaki T, Minoguchi K, Yokoe T, et a.l Allergen rush immunotherapy increases interleukin ( IL)-12 production and IL-12 receptor beta2 chain expression in patientswith allergic asthma. Cell Immuno,l 2004, 228: 20-26
134 Brunda MJ,Luistro L,Warrier RR,et al.Antitumor and antimetastatic activity of interkeukin-12 against murine tumors.J Exp Med,1993,46:5276-5281
135 Dinarello C A. Proinflammatory cytokines. Chest. 2000, 118: 503-508
136 Majamaa.H, Isolauri.E, Saxelin.M, Vesikari.T. Lactic acid bacteria in the treatment of acute rotavirus gastroenteritis. J.Pediatr.Gastroenterol.Nutr. 1995;20:333-338
137 Chihara J. Stress and immunoallergy〔J〕. Rinsho Byori,1998,46(6):587
138 Prete DG,Magy E,Romagnani S. Human Th1and Th2cell:Functional properties,mechanism of regulation and role in disease〔J〕. Lab Investig,1994,70:299
139 Perdigon G,Nader De Macios M,Ak,arez S,et a1.Effect of perorally administered lactobacilli on macrophage activation in mice.Infection and lmnmnity 1986,53:404-410
140 Perdigon G,Nader de Macias ME Alvarez S,et a1.Enhancement of jmmune response in mice fedⅥithStreptococcus thermophilus and Lactobacillus acidophilus Journal of Dairy.Science 1 987,70:9 1 9-926
141 Hatcher GE and Lambrecht RS.Augmentation of microphage phagocytic activity b3, cell—free extracts of selected lactic acid—producing bacteria.Journal Of Dairy Science 1 993,76:2485—2492
142 Marin ML,Tejada—Simon MV,and Lee JH.Stimulation of cytokine production in clonal macrophage and T—ceil models by Streptococcus thermophilus:Comparison with Bifidobac—teriuln sp.and Lactobacillus bulgaricus.Journal of Food Protection 1 998,6 1(7):859-864
143 Marin ML Tejada—Simon MV Murtha J,et a1.Effects of Lactobacillus spp.on cytokine production by raw 264 7macrophage and EL一4 thymoma cell lines Journal ol’FoodProtection,l997 60(I1):l 364-l370
144 Muller-Alouf H,AloufJ,Gerlach D.et a1.Comparatk,e study of cytokine release by human peripheral blood mononuclcar cells stimulated with Streptococcus pyogenes superantigeic erythrogenic toxins , heat—killed Streptococci , and lipopolys—accharide.Infection and Immunity,l 998,62(1 1):49 1 5-492 1
145 Tejada—Simon MV,Ustunol Z and Pestka JJ.Ex vivo effects of lactobacilli,streptococci,and Bifidobacteria on cytokine and nitric oxide production in a murine mode1. Journal of Food Protection,1 999,62(2):l 62-1 69
146 De Simone C and Vesely R. Enhancement of hlllnune response of murine Peyer’s patches by a diet supplementedⅥrith yogurt . Immunophan11acology and In1mLmotoxic0logy l987.9(11):87-l00
147 Trapp CL,Chang CC,Halpern GM,et al The influence of chronic yogurt consumptionon populations ofyoung and elderl3,adults.1ntemational Journal of lmmunophannacology, 1 993,9:53-64
148 Matsuzaki T,Yamazaki R Hashimoto S,ct al Antidiabetic effects of an ordl administration of Lactobacillus case in a non—insulin—dependent diabetes roellitus (NIDDM) model using KK—A super(y) mice Endocrine Journa1.1 997.44 (3):357-365
149 Matsuzaki T,Yamazaki R and Hashimoto S.The effect oforal feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice.Journal of Dairy Science,1998 81(1):48-53
150 Muscettola M,Massai L,Tanganelli C.et al Efects of Lactobacilli on interferon production in young and aged mice.Annals New York Academy of Sciences . 1 994.7 l 7:227-232
151 Chen T,lsomaki P,Rimpi lainen M,et al Human cytokine responses induced by gram—positive cell walls of normal intestinal microbiota.C linical and Experi mental lmmuno.1ogy,1999,1 18(2):261-267
152 Tejada—Simon MV and Pestka JJ Proinflammatorv cvtokil1e and nitric oxide induction in murine macrophages b3r cell wall and c3,toplasmic extracts of lactic acid bacteria Journal of Food Protection,1999,62(121:1435-1444
153 SHIDA KK,MAKINO A,MORISHITA K,et al.Lactobacillus casei inhibits antigen induced IgE secretion through regulation of cytokine production in murine splenocyte cultures[J].Int Arch Allergy Immunol,1998
154 LIMBK,MAHENDRANR,LEE YK,et al.Chemopreventive effect of Lactobacillus rhamnosus on growth of a subcutaneously implanted bladder caner cell line in the mouse[J].Jpn J Cancer Res,2002,93(1):36-41
155余保平,王伟岸.消化系疾病免疫学[M].北京:科学出版社,2000. 45-50
156赖新峰,王立生,潘令嘉,等.双歧杆菌对裸鼠腹腔巨噬细胞激活作用的初步研究[J].中国微生态学杂志,1999,1(6):336-337
157 Mosmann T R,S Sed.The expanding universeof T-cell subsets: Th1,Th2 and more[J].Immunol.Today,1996,17:138-146
158 Prete DG,Magy E,Romagnani S.Human Th1 and Th2 cell:Functional properties,mechanism of regulation and role in disease[J].Lab Investing,1994,70:299
159 Smith KA. Lowest dose interleukin-2 immunotherapy.Blood, 1993; 81∶1414
160 Chihara J.Stress and immunoallergy[J].Rinsho Byori,1998,46(6):587
161 Waldmann TA. The interleukin-2 receptor. J Biol Chem,1991; 266∶2681
162 Romagnani,S. The Th1/Th2 paradigm. Immunol Today.1997,18:263-266
163张宝元,马晓红,刘霞,等.双歧杆菌及其WPG对S180荷瘤鼠免疫调节和抑制作用的研究[J].中国微生态学杂志,2001,13(1):8-10
164魏小龙,茹祥斌,王青定,等.用竞争性RT-PCR方法定量检测p53基因的表达[J].军事医学科学院院刊,1999, 23(2):107
165 Kruis W.Review article:antibiotics and probiotics in inflammatory bowel disease[J]·Aliment Pharmacol Ther,2004,20(Supp14):75-78
166 Sartor RB.Therapeutic manipulation of the enteric microflora in inflammatory boweldiseases; antibiotics, probiotics, andprebiotics[J].Gastroenterol,2004,126:1620-1633
167 PollardM, SharonN. Response of the peyer’s in germ freemice to angyenic stimulation[J]. Infect Immune, 1970, 2(4): 96-100
168 Matsunaga K, Morita I, Oguchi Yet al·The effect of a biological response modifier, PSK, on the intestinal immune system in tumor bearing mice[J].Anticance Res,1987; 7(3 Pt B):509
169 Nakasaki H, TajimaT, MitomiTet al·Countermeasuresfor hypofunction of gut associated lymphoidtissue during TPN inrats[J].Nippon-Shokakibyo-Gakkai-Zasshi,1996; 93(11):806
170王立生,潘令嘉,施理,等.双岐杆菌对裸鼠腹腔巨嗜细胞产生IL-1、IL-6、IL-12的影响[J].中华微生物学和免疫学杂志,1998,18(5)∶373
171 Hart A L, Lammers K, Brigidi P et al. Modulation of human dendritic cell phenotype and function勿probiotic bacteria. Gut. 2004, 53: 1602-1609
172 Vinderola QMartar C, Perdigon G Role of intestinal epithelial cells in immune effects mediated by gram-positive probiotic bacteria: involvment of Toll-like receptor. Clin Diagn Lab Immunol. 2005, 9: 1075-1084
173 Menard S, Candalh C, Bambou J C et al. Lactic acid bacteria secrete metabolites retaining anti-inflammatory properties after intestinal transport. Gut, 2004, 53:821-828
174 FUKATSU K,SAKAMOTO S,HARA E,et al.Gut ischemia reperfusion affects gut macosal immunity:a possible mechanism for infectious complications after severe surgical insults[J].Crit care Med,2006,34(1):182-187
175 SPAHN TW,KUCHARZIK T.Modulating the intestinal immune system:the role of lymphotoxin and GALT organs[J].Gut,2004,53:456-465
176王涛,黎沾良,王亚平.全肠外营养对肠免疫功能影响的研究.中华外科杂志,1996,34(5)307-310
177周正任.浅谈黏膜免疫机制[J].中国微生态学杂志, 2000,12(16): 311-312
178 Salminen S, IsolauriE, SalminenE. Clinicaluse ofprobiotics for stabilizing the gutmucosalbarrier: successful strains and future challenges[J]. Antonie van Leeuwenhoek,1996, 99(2):347-358
179 FullerR, Perdigon G. Probiotics 3: Immunodulation by the gut microflora and probiotics[M ]. Netherlands: Kluwer Academic Publisher, 2000. 213-233
180 Salminen S,Bouley,C Boutron-Ruault MCet al.Functional food science and gastrointestinal physiology and function[J].Bri J Nutri,1998,80(1):147-171
181祁保民,高齐瑜.动物粘膜免疫系统[J].中国兽医杂志,1998,24(4):55-57
182 TakahashiM, Iwata S, YamazakiN,etal.Phagocytosisof the lactic acid bacteria byM cells in the rabbitPeyer’sPatchs[J]. Clin ElectronMicrosc, 1991, 24(2) : 5-6
183 FamularoG, MorettiS, Marcellin,ietal. Stimulation of immunity by probiotics[M]. London: Chapman andHil,l 1997. 133-161
184 Garriga M,Pascual M.Selection of lactobacilli for chicken probiotic adjuncts[J].J Appl Microbiol,1998,84(1):125~132
185杨洁彬,郭兴华,张篪,等.乳酸菌—生物学基础及应用.北京:中国轻工业出版社,1996. 179～180,246～249
186胡东良.乳酸菌的抗肿瘤、抗变异原及免疫增强作用.中国乳品工业,1997,25(6):12～
14
187 Yasui H,Shida K,Matsuzaki T,et al . Immunomodulatory function of lactic acid bacteria. Antonie van Leeuwenhoek 1999,76:383～389
188 Niedzielin K, Kordecki H, Birkenfeld B. A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome.Eur J Gastroenterol Hepatol. 2001,13(10):1143-7
189 Ohashi Y,Nakai S, Tsukamoto T,et al. Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Urol Int, 2002,68(4):273-280
190 Fukui M,Fujino T, Tsutsui K,et al. The tumor-preventing effect of amixture of several lactic acid bacteria on 1,2-dimethylhydrazine-induced colon carcinogenesis in mice. Oncol Rep, 2001,8(5):1073-1078
191 Balansky R, Gyosheva B, Ganchev G, et al. Inhibitory effects of freeze-dried milk fermented by selected Lactobacillus bulgaricus strains on car-cinogenesis induced by 1,2-dimethylhydrazine in rats and by diethylni trosamine in hamsters. Cancer Lett, 1999,147(1-2):125-137
192 Femia AP, Luceri C, Dolara P, et al. Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probioticsLactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane induced colon carcinogenesis in rats. Carcinogenesis, 2002,23(11):1953-1960
193 Budagov RS, U1’ianova LP, Chureeva LN, et al. Efficacy of a preparation based onLactobacillus acidophilus for protection from myelotoxic effects of ionizing radiation and antineoplastic cytostatics. Eksp Klin Far-makol, 2002,65(2):59-63.
194 Nicholson DW, Thornberry NA. Apoptosis: Life and death decisions [J]. Science, 2003, 299(6504): 214-215
195 RESTA-LENERTS, BARRE TTKE. Live probiotics protectin testina lepithelial cells from the effects of infection with entero in vasive Escherichiacoli(EIEC)[J].Gut,2003,52:988-997
196康白.新抗微生物战略[C]∥湖南省首届微生态学与第三届医院感染学术会会议论文集,1988:15-31
197 GRONL UND MM,ARVIL OMMIH ,KER OP,etal.Importance of interstinal colonization in the maturation of humoral immunityin earlyinfancy :aprospective follow-up study of healthy in fantsaged0-6months[J].Archives of Diseasein Childhood,2000,83:186-192
198陈文学,史俊华.双歧杆菌的研究进展[J].中国微生态学杂志,2000(12):298-300
199 Yuya Y, Manabu K, Daishiro I, et al. Involvement of doxorubicin-induced Fas expression in the antitumor effect of doxorubicin on Lewis lung carcinoma in vivo[J]. International Immunopharma cology, 2005,5: 281-288
200 Kato I, Tanaka K, Yokokura T. Lactic acid bacterium potently induces the production of interleukin-12 and interferon-γby mouse splenocytes.Int J Immunophamacol, 1999,21(2):121-131
201 Takagi A,Matsuzaki T, Sato M, et al. Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microor granism. Carcinogenesis,2001,22(4):599-605
202陈慰峰.医学免疫学(第三版)[M].北京:人民卫生出版社,2001:81-84
203 Kuboya T, McNamaraDM, Wang JJ,etal. Effects of tumornecrosis factors gene polymorphism on patientswith congestive heart failure. Circulation. 1998, 97(25): 2499
204 Browning J, Ribolini A. Study on the differing effects of tumor necrosis factor and lymphotoxin on the growth of several human tumor lines. J Immunol, 1992,77:411
205 Seow SW, Rahmat JN, Mohamed AA, et al. Lactobacillus species is more cytotoxic to human bladder cancer cells than Mycobacterium Bovis(bacillus Calmette-Guerin).J Urol, 2002,168(5):2236-2239
206 Martin S T,Green D R·Apoptosis and cancer: the failure of control son cell death and cell survival·CRC Cit Rev Oncol Hematol,1995,18(2):137-153
207 Rosse T, Olivier R, Monney L,et al. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c [J]. Nature, 1998, 391(6666): 496-499
208 Guo B, Zhai D, Cabezas E,et al. Humanin peptide suppresses apoptosis by interferingwith Bax activation [J]. Nature, 2003,423(6938): 456-461
209崔玉芳,杨红,高亚兵,等.辐射诱发小鼠淋巴结细胞凋亡特征和意义的研究.中华放射医学与防护杂志,2001,21:6365
210 Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death [J]. Cell, 1993, 74(4): 609-619
211 Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death·Cell, 1993,74(4):609-619
212 Yi X, Yin XM, Dong Z·Inhibition of Bid-induced apoptosis by Bcl-2·tBid insertion,Bax translocation,and Bax/Bak oligomerization suppressed·J Biol Chem, 2003, 278(19):16992-16999
213 Bareton GB, Piebol dJ,Christot foris G,etal. ApoPtosis and immunohis toehemieal Bel2ex ressionin colore ctaladenomas andeareinomas,aspectso fearino gensisand Prognostic significanee[J].Caneer,1996;77(2):255-264
214 Hockenbe DM.Bel一2ineancer,develoPmentand aPOPtosis[J].CellSei,1994,18(s):51-59
215 Huang Y,RS ,Reed JC,etal. Estronin ereasesintra cellular P26 to PZI BaX ratosan dinhibitstaxo lindueed aPoPtosis of human breasteaneer MCF7ceells[J].BreastCancer ResTreat,1997:42(l):73-81
216 Reed J C.Bcl-2 and the regulation of programmed cell death〔J〕. J CellBio,l 1993,
75(2): 241
217 MiyashitaT,Reed JC.Bcl-2 oncoprotein block chemotherapy induced apoptosis in a human leukemia cell line〔J〕. Blood,1993, 81(1): 151
218 Krajewski S, Krajewska M, Shabaik A, et a.l Immunohisto chemicaldetermination of in vivo distribution ofBax, a dominant inhibitor ofBcl-2〔J〕.Am J Patho,l 1994, 145: 1323
219李勇,潘立峰.化疗诱导人胃癌细胞凋亡及Bcl-2、Bax基因蛋白表达变化的研究〔J〕.河北医科大学学报, 2001,22(3): 163
220 SultanaH,Kigawa J,KanamoriY. Chemosensitivity and p53-Bax pathway-mediated apoptosis in patientswith uterine cervical cancer〔J〕.Ann Onco,l 2003, 14(2): 214.
221 Krest I, Keusgen M. Quality of Herbal Remedies from Allium sativum: Differences between Alliinase from Garlic Powder and Fresh Garlic[J]. Planta Medica, 1999,65:1339-1343
222 Siegers CP, Stefffen B, Robke A, et al. The effects of garlic preparations against human tumor cell proliferation[J]. Phytomedicine, 1999,6:7-11.
223 Hirsch K, Danilenko M, Giat J, et al. Effect of purified allicin,the major ingredient of freshly crushed garlic, on cancer cell proliferation[J]. Nutr Cancer, 2000,38:245-254
224 Takeda K, Smyth M J, Cretney E,et al. Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development [J].J Exp Med, 2002, 195(2): 161-169.
225 Yu C L, Ye T X, Lu D Y,et al.Modern Medical Immunology(现代医学免疫学) [M]. Shanghai: Shanghai University of Medical Science Publishing House, 1998
226 Ma Y, Ma Y Z, Zhang J Y,et al. Regulatory effects of polysaccharide Fb from Huangmo on immunological function in mice [J].J Jilin Univ:Med Ed(吉林大学学报:医学版),2005, 31(5): 692-695
227 asegawa H, Suzuki R, Nagaoka T,et al. Prevention of growth and metastasis of murine melanorr a through enbanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatrio [J].Biol Pharm Bull, 2002, 25(7): 861-866
228 Tsai Y J, Chen I L, Horng L Y,et al. Induction of differentiation in rat C6 glioma cells with Saiko saponins [J].Phytother Res, 2002, 16(2): 117-121
229 Bruck I,O DonnellM. The ring-type polymerase sliding clamp family[J].Genome Bio,l 2001, 2(1):REVIEWS3001
230 NishitaniH,Lygerou Z.Control ofDNA replication licensing in a cell cycle[J].Genes to cells, 2002, 7(6): 523-534
231 StevauxO,Dyson NJ. A revised picture of the E2F transcript tionalnetwork and RB function[J].CurrOpin cellBio, 2002, 14(6): 684-691
232 TsurimotoT. PCNA binding proteins[J]. FrontBiocsc,i 1999,4:D849-858
233 Habib MR, Joel AH, Qing F. Modulation of apoptosis by nitric oxide:implications in myocardial ischemia and heart failure[J].Pharmacology&Therapeutics, 2005, 106: 147-162
234 Castellon E, Clementi M, Hitschfeld C, Sanchez C, Benitez D, Saenz L, et al.Effect of leuprolide and cetrorelix on cell growth, apoptosis, and GnRH receptor expression in primary cell cultures from human prostate carcinoma [J].Cancer Invest. 2006, 24(3):261-268
235 Fan HT, Xiong XY, Cao W, Gao ZB, Li XQ, Jia M, et al. Effects of proliferation inhibition and apoptosis of resveratrol trinicotinate on HepG2 cells and its mechanism[J].Chin J Clin pharmacol Then 2006, 11 (5 ):540-544
236 Zhan HX,Zhong CG,Xu SQ,Li HW. Relationships of hexavalent chromium( VI)-induced apoptosis,oxidadve damage and expressions of p53 and caspase3 in L-02 hepatocytes [J].Chin J Pharmacol Toxicol, 2006, 20 (2):144-151
237 Zhan J, Yang J, Tang HB. Inhibitory effect of isoliquiritigenin on proliferation of human cervical cancer cells in vitro and in vivo [J].Chin J Pharmacol Toxicoi, 2005,19(6):436-442
238唐忠志,付立波,唐瑛.丹参酮ⅡA抑制人肝癌细胞的生长及诱导其凋亡的实验研究[J] .第三军医大学学报,2003,25(9):774-776
239 Naryzhny SN,Desouza LV,Siu KW,et al.Characterization of the human proliferating cell nuclear antigen physico-chemical properties:aspects of double trimer stability[J].Biochem Cell Biol,2006,84(5):669-676
240岳辉,张宁,冯新莉,等.胰腺癌组织中p57kip2、Cyclin E和PCNA表达与临床病理因素的关系[J].癌症,2003,22(7):705-709
241 Oketani M,Kohara K,Tuvdendorj D,et a1.Inhibition by arsenictrioxide of human hepatoma cell growth[J].Cancer Lett,2002,183(2):147-153
242 Blain SW,Scher HI,Cordon-Cardo C,et a1.p27 as a target for cancer therapeutics[J].Cancer Cell,2003,3(2):111-115
243 Ganoth D,Bornstein G,Ko TK,et al.The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27[J].Nat Cell Biol,2001,3(3):321-324
244 Yokoi S,Yasui K,Saito-Ohara F,et al.A novel target gene,SKP2,within the 5p13 amplicon that is frequently detected in small cell lung cancers[J].Am J Pathol,2002,161(1):207-216
245 Kuznetosv G, Towle MJ, Cheng H, et al. Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389[J].Cancer Res,2004,64(16):5760-5766
246云月英,王立平,陈永福,孟和毕力格,张和平.喂饲Lactobacillus casei Zhang对大鼠体内脂质代谢的影响.微生物学通报, 2006. 33(3) : 60-64
247张和平,张七斤,孟和毕力格,任贵强. L.casei zhang对小鼠T淋巴细胞亚群及血清IgG和肠黏膜SigA的影响.中国乳品工业, 2006. 34(10): 4-8
248托娅,苏雅勒玛,张和平.乳杆菌L.casei zhang对小鼠血清中细胞因子水平的影响.食品科学, 2006, 27(11): 488-491
249王俊国,孟和毕力格,张和平*,陈永福,包秋华.干酪乳杆菌Zhang对大鼠抗氧化能力的影响[J].营养学报,2008,30(1):1-6