慢性宫内缺氧对子代兔非酒精性脂肪性肝病的影响及黄芪的保护作用
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摘要
目的:
研究慢性宫内缺氧对子代兔非酒精性脂肪性肝病的影响,并初步探讨黄芪的保护作用。
方法:
将新西兰孕兔24只于孕第10天随机分为3组,即慢性宫内缺氧组(12%O_2)、中药黄芪组(12%O_2)、正常对照组(21%O_),每组各8只。待孕兔生下子代兔后,每窝中随机取1只雄性仔兔,共24只仔兔,分组同上,母乳喂养至3月龄后,再给予普通饲料喂养至6月龄。第6个月龄末,处死动物,留取标本,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)浓度,肿瘤坏死因子-α(TNF-α)浓度,行肝组织HE染色及TNF-α多克隆抗体免疫组化染色,观察肝组织形态学表现及TNF-α表达情况。
结果:
1.与正常对照组相比,慢性宫内缺氧组血清TG、TC、LDL-C、TNF-α浓度增高,血清HD降低,统计学上有显著性差异(P＜0.01);与正常对照组相比,中药黄芪组血清TG、LDL-C增高,血清HDL-C降低,统计学上有显著性差异(P＜0.01);与慢性宫内缺氧组比较,中药黄芪组血清TG、TC、LDL-C、TNF-α浓度降低,血清HDL-C增高,统计学上有显著性差异(P＜0.01);与正常对照组相比,中药黄芪组血清TC、TNF-α浓度增高,但无显著性差异(P＞0.05)。与正常对照组相比,中药黄芪组、慢性宫内缺氧组血清AST、ALT浓度依次增高,但三组之间两两比较,统计学上均无显著性差异(P＞0.05)。
2.正常对照组、中药黄芪组、慢性宫内缺氧组三组之间相比,肝组织HE染色、TNF-α表达光镜下表现明显不同;肝组织脂肪变性程度比较,慢性宫内缺氧组较严重,正常对照组无明显脂肪变性,中药黄芪组脂肪变性程度介于两组之间,三组之间两两比较,统计学上有显著性差异(P＜0.01)。
结论:
1.本实验成功制备了子代兔慢性宫内缺氧模型。
2.慢性宫内缺氧可引起子代兔主要器官宫内不适当比例生长及低出生体重。
3.慢性宫内缺氧与子代兔成年NAFLD的发生密切相关,可增加成年期NAFLD发生的易感性,可能是成年期NAFLD发生的一个重要影响因素。
4.黄芪可减轻慢性宫内缺氧引起成年兔NAFLD发生的损伤,对慢性宫内缺氧引起的成年兔NAFLD发生的损伤有一定的防护作用。
Objective
To investigate the effect of chronic intrauterine hypoxia on nonalcoholic fatty liver disease in adult rabbit offspring and the protective function of Astragalus.
Methods
Twenty-four New-Zealand rabbits were randomly divided into 3 groups on gestation day 10: chronic intrauterine hypoxia group(CIH,12%O_2,n=8),Astragalus group(CIH&A,12%O_2, n=8) and normal control(NC,21%O_2,n=8).After delivery,one male offspring of each mother rabbit was selected and breast-fed for three months.Then they were fed on normal diet from the fourth month to the sixth month.At the end of the sixth month,serum alanine transaminase (ALT)、aspartate transaminase(AST)、triglyceride(TG)、cholesterol(TC)、low density lipoprotein-cholesterol(LDL-C),high density lipoprotein- cholesterol(HDL-C),tumor necrosis-α(TNF-α) were measured.The rabbits' fatty livers were stained with hematoxylin-eosin and immunohistochemistry and image the expression of TNF-αin the liver.
Results
1.Compared with the normal group,the level of serum TG、TC、LDL-C、TNF-αin chronic intrauterine hypoxia group were significantly increased,but the level of serum HDL-C was decreased.There was much significant difference between the two groups(P＜0.05).Compared with the normal group,the level of serum TG、LDL-C in Astragalus group were significantly increased,but the level of serum HDL-C was decreased.There was much significant difference between the two groups(P＜0.05).Compared with chronic intrauterine hypoxia group,the level of serum TG、TC、LDL-C、TNF-αin Astragalus group were significantly decreased,but the level of serum HDL-C was increased.There was much significant difference between the two groups(P＜0.05).Compared with the normal group,the level of serum TC and TNF-αwas increased,but there was no significant difference between the two groups(P＞0.05).Compared with the normal group,the level of serum AST、ALT in chronic intrauterine hypoxia group and Astragalus group were significantly increased,but there was no significant difference between the three groups(P＞0.05).
2.There were significantly different in hepatic tissue HE stain and TNF-αexpression among CIH,CIH & A and NC groups.According to the degree of hepatic tissue fatty degeneration,CIH group is the highest,and NC group is the lowest.However there were significantly different in the degree of hepatic tissue fatty degeneration among the three groups(P＞0.05).
Conclusion
1.This experiment has successfully produced the model of chronic intrauterine hypoxia.
2.Chronic intrauterine hypoxia can lead to intrauterine growth retardation(IUGR)and lower body birth-weight.
3.Chronic intrauterine hypoxia is an important influence factor resulting in nonalcoholic fatty liver disease in adult rabbit offspring.Chronic intrauterine hypoxia may increase the risk of nonalcoholic fatty liver in adult rabbit offspring.
4.Astragalus can reduce the damage of nonalcoholic fatty liver disease in adult rabbit offspring which is caused by chronic intrauterine hypoxia and protect rabbit offspring from chronic intrauterine hypoxia.
研究慢性宫内缺氧对子代兔非酒精性脂肪性肝病的影响,并初步探讨黄芪的保护作用。
方法:
将新西兰孕兔24只于孕第10天随机分为3组,即慢性宫内缺氧组(12%O_2)、中药黄芪组(12%O_2)、正常对照组(21%O_),每组各8只。待孕兔生下子代兔后,每窝中随机取1只雄性仔兔,共24只仔兔,分组同上,母乳喂养至3月龄后,再给予普通饲料喂养至6月龄。第6个月龄末,处死动物,留取标本,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)浓度,肿瘤坏死因子-α(TNF-α)浓度,行肝组织HE染色及TNF-α多克隆抗体免疫组化染色,观察肝组织形态学表现及TNF-α表达情况。
结果:
1.与正常对照组相比,慢性宫内缺氧组血清TG、TC、LDL-C、TNF-α浓度增高,血清HD降低,统计学上有显著性差异(P＜0.01);与正常对照组相比,中药黄芪组血清TG、LDL-C增高,血清HDL-C降低,统计学上有显著性差异(P＜0.01);与慢性宫内缺氧组比较,中药黄芪组血清TG、TC、LDL-C、TNF-α浓度降低,血清HDL-C增高,统计学上有显著性差异(P＜0.01);与正常对照组相比,中药黄芪组血清TC、TNF-α浓度增高,但无显著性差异(P＞0.05)。与正常对照组相比,中药黄芪组、慢性宫内缺氧组血清AST、ALT浓度依次增高,但三组之间两两比较,统计学上均无显著性差异(P＞0.05)。
2.正常对照组、中药黄芪组、慢性宫内缺氧组三组之间相比,肝组织HE染色、TNF-α表达光镜下表现明显不同;肝组织脂肪变性程度比较,慢性宫内缺氧组较严重,正常对照组无明显脂肪变性,中药黄芪组脂肪变性程度介于两组之间,三组之间两两比较,统计学上有显著性差异(P＜0.01)。
结论:
1.本实验成功制备了子代兔慢性宫内缺氧模型。
2.慢性宫内缺氧可引起子代兔主要器官宫内不适当比例生长及低出生体重。
3.慢性宫内缺氧与子代兔成年NAFLD的发生密切相关,可增加成年期NAFLD发生的易感性,可能是成年期NAFLD发生的一个重要影响因素。
4.黄芪可减轻慢性宫内缺氧引起成年兔NAFLD发生的损伤,对慢性宫内缺氧引起的成年兔NAFLD发生的损伤有一定的防护作用。
Objective
To investigate the effect of chronic intrauterine hypoxia on nonalcoholic fatty liver disease in adult rabbit offspring and the protective function of Astragalus.
Methods
Twenty-four New-Zealand rabbits were randomly divided into 3 groups on gestation day 10: chronic intrauterine hypoxia group(CIH,12%O_2,n=8),Astragalus group(CIH&A,12%O_2, n=8) and normal control(NC,21%O_2,n=8).After delivery,one male offspring of each mother rabbit was selected and breast-fed for three months.Then they were fed on normal diet from the fourth month to the sixth month.At the end of the sixth month,serum alanine transaminase (ALT)、aspartate transaminase(AST)、triglyceride(TG)、cholesterol(TC)、low density lipoprotein-cholesterol(LDL-C),high density lipoprotein- cholesterol(HDL-C),tumor necrosis-α(TNF-α) were measured.The rabbits' fatty livers were stained with hematoxylin-eosin and immunohistochemistry and image the expression of TNF-αin the liver.
Results
1.Compared with the normal group,the level of serum TG、TC、LDL-C、TNF-αin chronic intrauterine hypoxia group were significantly increased,but the level of serum HDL-C was decreased.There was much significant difference between the two groups(P＜0.05).Compared with the normal group,the level of serum TG、LDL-C in Astragalus group were significantly increased,but the level of serum HDL-C was decreased.There was much significant difference between the two groups(P＜0.05).Compared with chronic intrauterine hypoxia group,the level of serum TG、TC、LDL-C、TNF-αin Astragalus group were significantly decreased,but the level of serum HDL-C was increased.There was much significant difference between the two groups(P＜0.05).Compared with the normal group,the level of serum TC and TNF-αwas increased,but there was no significant difference between the two groups(P＞0.05).Compared with the normal group,the level of serum AST、ALT in chronic intrauterine hypoxia group and Astragalus group were significantly increased,but there was no significant difference between the three groups(P＞0.05).
2.There were significantly different in hepatic tissue HE stain and TNF-αexpression among CIH,CIH & A and NC groups.According to the degree of hepatic tissue fatty degeneration,CIH group is the highest,and NC group is the lowest.However there were significantly different in the degree of hepatic tissue fatty degeneration among the three groups(P＞0.05).
Conclusion
1.This experiment has successfully produced the model of chronic intrauterine hypoxia.
2.Chronic intrauterine hypoxia can lead to intrauterine growth retardation(IUGR)and lower body birth-weight.
3.Chronic intrauterine hypoxia is an important influence factor resulting in nonalcoholic fatty liver disease in adult rabbit offspring.Chronic intrauterine hypoxia may increase the risk of nonalcoholic fatty liver in adult rabbit offspring.
4.Astragalus can reduce the damage of nonalcoholic fatty liver disease in adult rabbit offspring which is caused by chronic intrauterine hypoxia and protect rabbit offspring from chronic intrauterine hypoxia.
引文
[1]范建高.非酒精性脂肪肝的病因利发病机制[J].胃肠病学,2003,8(6):363-365
[2]Barker D J,Martyn CN,Osmond C,et al.Growth in utero and serum cholesterol concentrations in adult life.Br Meal,1993,307:1524-1527.
[3]崔蕴璞.低出生体重与胰岛素抵抗[J].国外医学儿科学分册,2003,30(1):61-62
[4]Curhan GC,Willett WC,Rimm EB,et al.Birth weight and adult hypertension,diabetes mellitus,and obesity in US men.Circulation,1996,12:3246-3250
[5]Martyn CN,Barker DJP,Jespersen S,et al..Growth in utero,adult blood pressure,and arterial compliance.Br Heart,1995,73:116-121
[6]Fall CHD,et al.Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease.Br.Med,1992,304:801-805
[7]Barker,DJP,Martyn CN,Osmond C,et al.Growth in utero and serum cholesterol concentrations in adult life.Br Med,1993,6918:1524-1527
[8]Barker,DJP,et al.Relation of fetal and infant growth to plasma fibrinogen and factor Ⅶ concentrations in adult life.Br.Med.1992,304:148-152
[9]Rudolph AM.The fetal circulation and its response to stress.Dev Physiol,1984,6:11-19
[10]Berry LM,Polk DH,lkegami M,et al.Prterm newborn lamb renal and cardiovascular responses aider fetal or maternal antenatal betamethasone.Am J Physiol,1997,272:1972-1979
[11]Barker,DJP,The Weilcome Foundation Lecture.The fetal origins of adult disease.Proc R Soc Lond B Biol Sci,1995,262:37-43
[12]West-Eberhard,MJ.Phenotypic plasticity and the origins of diversity.Annu Rev Ecol Syst,1989,20:249-278
[13]Gagnon R.Placental insufficiency and its consequences.Eur J Obstet Gynecol Reprod Biol,2003,110:99-107
[14]Lucas A.Programming by nutrition in man;in:Conning D(ed):Early diet,Later consequences.London:British Nutrition Federation,1992:24-28.
[15]Moore LG.Human ge.netic adaptation to high altitude.High Alt Med Biol,2001,2:257-279.
[16]Kwong,W.Y.et al.Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension.Development.2000,127:4195-4202.
[17]苏瑞娟,吕国荣,等.宫内缺氧对子代大鼠脂肪肝发病的影响[J].世界华人消化杂志,2006,14(11):1048-1051
[18]沈浪泳.应用《黄帝内经》“治未病”理论防治消渴病[J].中国医药学报,2003,18(10):593-595
[19]崔闽鲁.“肾为先天之本”与“治未病”[J].福建省优秀中医临床人才研修项目学员论文荟萃,2007,12:198-200
[20]Mogren I,Hogberg U,et al.Fetal exposure,heredity and risk indicators for cardiovascular disease in a Swedish welfare cohort.Int Epidemiol 2001,4:853-862.
[21]Giussani DA,Phillips PS,Anstee S,et al.Effects of attitude versus economic status on birth weight and body shape at birth.Pediatr Res,2001,49:490-494
[22]Williams SJ,Campbell ME,McMillen IC,et al.Differential effects of maternal hypoxia or nutrient restriction on carotid and femoral vascular function in neonatal rats.Am J Physiol Regul Integr Comp Physiol,2005,288:360-367
[23]Kitanaka T,Alonso JG,Gilbert RD,et al.Fetal responses to long-term hypoxemia in sheep.Am J Physiol,1989,256:1348-1354
[24]Okamura K,Murotsuki J,Watanabe T,et al.Relation between fetal blood gas levels and the outcome of babies in severe preeclampsia.Tohoku,2002,208:330-333
[25]Moore LG.Fetal growth restriction and maternal oxygen transport during high altitude pregnancy.High Alt Med Biol,2003,4:141-156
[26]Moore LG.Human genetic adaptation to high altitude.High Alt Med Biol,2001,2:257-279
[27]Barker DJ,Meade TW,Fall CH,Relation of fetal and infant growth to plasma fibrinogen and factor Ⅶconcentrations in adult life.Br Med,1992,304:148-152
[28]Barker D J,Martyn CN,Osmond C,et al.Abnormal liver growth in utero and death from coronary heart disease.Br Med,1995,310:703-704
[29]Kiserud T,Ozaki T,Nishina H,et al.Effect of NO,phenylephrine,and hypoxemia on ductus venosus diameter in fetal sheep.Am J Physiol Heart Circ Physiol,2000,279:1166-1171.
[30]吴斌,林乔,王米渠.论中医遗传学研究的重要性[J].上海中医药杂志,2004,3(38):3-5
[31]施观芬.试论《周易》哲学对中医养生学的影响[J].易学与自然科学,2000,1(4):6-10
[32]吴敦序.中医基础理论[M].上海科学技术出版社,1998,67-68
[33]御史译,李时珍著.《本草纲目》[M].北京科学技术出版社,2006,196
[34]袁红霞,陈艳春.黄芪的现代药理研究及其临床应用[J].山东中医药大学学报,2000,24(5):15-16
[35]祝晓玲,祝彼得.黄芪注射液影响贫血小鼠粒单系、红系造血及作用机制的探讨[J].中国中西医结合急救杂志,2001,8(5):284-286
[36]张仲平,洪介民.黄芪多糖对体外人骨髓造血祖细胞生成的影响[J].中药药理与临床,2000,16(1):16-17
[37]高建,徐先祥,等.黄芪总皂苷抗血栓形成作用实验研究[J].中成药,2002,24(2):116-118
[38]石刚刚,陈锦香,李长潮,等.黄芪注射液对冠状动脉直接作用的研究[J].中药新药与临床药理,1999,10(1):38-39
[39]王若光,李春梅,尤昭玲,等.黄芪丹参复方成分对一氧化氮合成阻滞孕鼠胎盘超微形态影响研究[J].中华现代中西医杂志,2005,3(2):516-518
[40]朴春梅.黄芪对糖尿病的药理机理研究近况[J].云南中医中药杂志,2005,26(2):54-55
[41]汪德清,沈文梅,田亚平,等.黄芪有效成分对氧自由基清除作用的研究[J].生物化学与生物物理进展,1996,23(3):260-262
[42]王建新,梅广林,胡卫东.黄芪在肝脏缺血—再灌注损伤中保护作用的研究[J].南通大学学报(医学版),2005:25(3):161-163
[43]裴林,刘唤荣,张少丹,等.黄芪对缺氧缺血性脑损伤幼鼠一氧化氮、丙二醛含量的影响[J].中国中西医结合急救杂志,2001,8(4):222-223
[44]刘玉莲、杨从忠.黄芪药理作用概述[J].综述报告,2004,13(10):79-80
[45]张建新.黄芪对小鼠免疫功能影响的研究[J].时珍国医国药,2000,11(6):488-449
[46]杨林辉,陈东风.TNF-a与非酒精性脂肪肝[J].现代医药卫生,2007,23(10):55-57
[47]艾正琳,陈东风.非酒精性脂肪肝与胰岛素抵抗[J].现代医药卫生,2005,21(1):33-35.
[48]尤鹏.非酒精脂肪肝炎发病机制的研究进展[J].北京大学学报,2003,5(2):97-99
[49]张瑞红,黄宇,张雯等振.抑制血清TNF-a对大鼠脂肪肝的影响的实验研究[J].临床和实验医学杂志,2006,5(8):1069-1071
[50]王广华.非酒精性脂肪肝发病机制研究进展[J].中国康复理论与实践,2004,10(4):243-244
[51]蔡葵,何玉怡.非酒精性脂肪肝与代谢性紊乱的关系[J].实用医技杂志,2006,13,(15):2636-2637
[1]袁红霞,陈艳春.黄芪的现代药理研究及其临床应用[J].山东中医药大学学报,2000,24(5):15-16
[2]朱兆洪,丁柱.黄芪对脑缺血缺氧的保护作用机制[J].吉林中医药,2005,25(8):61-62
[3]王志新,姚金凤,张瑞锋,等.黄芪对神经细胞缺氧缺血损伤的保护作用[J].河南大学学报(医学版),2005,24(3):61-62
[4]裴林,刘唤荣,张少丹,等.黄芪对缺氧缺血性脑损伤幼鼠一氧化氮、丙二醛含量的影响[J].中国中西医结合急救杂志,2001,8(4):222-223
[5]李论,柯俐,彭定凤.黄芪对心肌细胞缺氧时的作用研究[J].中西医结合心血管病杂志,2003,1(2):79-80
[6]石刚刚,陈锦香,李长潮,等.黄芪注射液对冠状动脉直接作用的研究[J].中药新药与临床药理,1999,10(1):38-39
[7]章辰芳,孔繁智,柴秀娟,等.黄芪生脉颗粒剂对小型猪实验性心肌缺血时的影响[J].中国实验方剂学杂志,1998,4(5):22-24
[8]颜光涛,郝秀,王录熳,等.失血性休克再灌注损伤血浆脂酶A2及其水解产物的变化[J].中国病理生理杂志,1998.14(4):414-415
[9]王建新,梅广林,胡卫东.黄芪在肝脏缺血—再灌注损伤中保护作用的研究[J].南通大学学报(医学版),2005:25(3):161-163
[10]蒋晓峰,吴毅泰,李江涛,等.黄芪对大鼠急性肾缺血再灌注损伤的保护作用[J]. 基础医学与临床基础医学与临床,2002,22(5):479-481
[11]王迎新,李华,陈敏珠.黄芪提取物的抗疲劳和耐缺氧作用[J].中国实用医药杂志,2007,2(9):43-44
[12]王戈博,施文芙,张海林,等.黄芪的抗缺氧效应及对血红蛋白含量和动物动脉血压的影响[J].甘肃高师学报,2002,7(5):48-49
[13]柳济成,安昌善,严春花,等.黄芪对低氧性肺动脉高压大鼠肺组织中超氧化物歧化酶、丙二醛的影响[J].延边大学学报,2002,5(2):42-44
[14]何建国,荆志成,顾晴,等.缺氧性肺动脉高压大鼠泡内肺动脉与右心室胶原蛋白表达及黄芪的干预作用[J].中华医学杂志,1999,79(9):654-656
[15]王若光,李春梅,尤昭玲,等.黄芪丹参复方成分对一氧化氮合成阻滞孕鼠胎盘超微形态影响研究[J].中华现代中西医杂志,2005,3(2):516-518
[16]王红光.清开灵和黄芪注射液治疗新生儿缺氧缺血性脑病[J].中国乡村医药杂志,2001,8(12):19-20
[17]张印,焦华梅,王发渭.补阳还五汤治疗心脑血管疾病的辨治分析[J].中国临床康复,2005,9(27):26-27
[18]朱晔,蒋屏.益气补肾活血法佐治小儿肾病综合征的临床观察[J].湖南中医药大学学报,2007,27(2):60-61
[19]潘永峰,李风皖.清开灵加黄芪治疗酒精性肝病的疗效分析[J].肝脏,2001,6,(2):141-142
[20]柏干苹,李廷谦.益气活血药对慢性缺氧大鼠肺血流动力学的影响[J].中国临床康复,2004,8(4):1710-1711
[2]Barker D J,Martyn CN,Osmond C,et al.Growth in utero and serum cholesterol concentrations in adult life.Br Meal,1993,307:1524-1527.
[3]崔蕴璞.低出生体重与胰岛素抵抗[J].国外医学儿科学分册,2003,30(1):61-62
[4]Curhan GC,Willett WC,Rimm EB,et al.Birth weight and adult hypertension,diabetes mellitus,and obesity in US men.Circulation,1996,12:3246-3250
[5]Martyn CN,Barker DJP,Jespersen S,et al..Growth in utero,adult blood pressure,and arterial compliance.Br Heart,1995,73:116-121
[6]Fall CHD,et al.Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease.Br.Med,1992,304:801-805
[7]Barker,DJP,Martyn CN,Osmond C,et al.Growth in utero and serum cholesterol concentrations in adult life.Br Med,1993,6918:1524-1527
[8]Barker,DJP,et al.Relation of fetal and infant growth to plasma fibrinogen and factor Ⅶ concentrations in adult life.Br.Med.1992,304:148-152
[9]Rudolph AM.The fetal circulation and its response to stress.Dev Physiol,1984,6:11-19
[10]Berry LM,Polk DH,lkegami M,et al.Prterm newborn lamb renal and cardiovascular responses aider fetal or maternal antenatal betamethasone.Am J Physiol,1997,272:1972-1979
[11]Barker,DJP,The Weilcome Foundation Lecture.The fetal origins of adult disease.Proc R Soc Lond B Biol Sci,1995,262:37-43
[12]West-Eberhard,MJ.Phenotypic plasticity and the origins of diversity.Annu Rev Ecol Syst,1989,20:249-278
[13]Gagnon R.Placental insufficiency and its consequences.Eur J Obstet Gynecol Reprod Biol,2003,110:99-107
[14]Lucas A.Programming by nutrition in man;in:Conning D(ed):Early diet,Later consequences.London:British Nutrition Federation,1992:24-28.
[15]Moore LG.Human ge.netic adaptation to high altitude.High Alt Med Biol,2001,2:257-279.
[16]Kwong,W.Y.et al.Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension.Development.2000,127:4195-4202.
[17]苏瑞娟,吕国荣,等.宫内缺氧对子代大鼠脂肪肝发病的影响[J].世界华人消化杂志,2006,14(11):1048-1051
[18]沈浪泳.应用《黄帝内经》“治未病”理论防治消渴病[J].中国医药学报,2003,18(10):593-595
[19]崔闽鲁.“肾为先天之本”与“治未病”[J].福建省优秀中医临床人才研修项目学员论文荟萃,2007,12:198-200
[20]Mogren I,Hogberg U,et al.Fetal exposure,heredity and risk indicators for cardiovascular disease in a Swedish welfare cohort.Int Epidemiol 2001,4:853-862.
[21]Giussani DA,Phillips PS,Anstee S,et al.Effects of attitude versus economic status on birth weight and body shape at birth.Pediatr Res,2001,49:490-494
[22]Williams SJ,Campbell ME,McMillen IC,et al.Differential effects of maternal hypoxia or nutrient restriction on carotid and femoral vascular function in neonatal rats.Am J Physiol Regul Integr Comp Physiol,2005,288:360-367
[23]Kitanaka T,Alonso JG,Gilbert RD,et al.Fetal responses to long-term hypoxemia in sheep.Am J Physiol,1989,256:1348-1354
[24]Okamura K,Murotsuki J,Watanabe T,et al.Relation between fetal blood gas levels and the outcome of babies in severe preeclampsia.Tohoku,2002,208:330-333
[25]Moore LG.Fetal growth restriction and maternal oxygen transport during high altitude pregnancy.High Alt Med Biol,2003,4:141-156
[26]Moore LG.Human genetic adaptation to high altitude.High Alt Med Biol,2001,2:257-279
[27]Barker DJ,Meade TW,Fall CH,Relation of fetal and infant growth to plasma fibrinogen and factor Ⅶconcentrations in adult life.Br Med,1992,304:148-152
[28]Barker D J,Martyn CN,Osmond C,et al.Abnormal liver growth in utero and death from coronary heart disease.Br Med,1995,310:703-704
[29]Kiserud T,Ozaki T,Nishina H,et al.Effect of NO,phenylephrine,and hypoxemia on ductus venosus diameter in fetal sheep.Am J Physiol Heart Circ Physiol,2000,279:1166-1171.
[30]吴斌,林乔,王米渠.论中医遗传学研究的重要性[J].上海中医药杂志,2004,3(38):3-5
[31]施观芬.试论《周易》哲学对中医养生学的影响[J].易学与自然科学,2000,1(4):6-10
[32]吴敦序.中医基础理论[M].上海科学技术出版社,1998,67-68
[33]御史译,李时珍著.《本草纲目》[M].北京科学技术出版社,2006,196
[34]袁红霞,陈艳春.黄芪的现代药理研究及其临床应用[J].山东中医药大学学报,2000,24(5):15-16
[35]祝晓玲,祝彼得.黄芪注射液影响贫血小鼠粒单系、红系造血及作用机制的探讨[J].中国中西医结合急救杂志,2001,8(5):284-286
[36]张仲平,洪介民.黄芪多糖对体外人骨髓造血祖细胞生成的影响[J].中药药理与临床,2000,16(1):16-17
[37]高建,徐先祥,等.黄芪总皂苷抗血栓形成作用实验研究[J].中成药,2002,24(2):116-118
[38]石刚刚,陈锦香,李长潮,等.黄芪注射液对冠状动脉直接作用的研究[J].中药新药与临床药理,1999,10(1):38-39
[39]王若光,李春梅,尤昭玲,等.黄芪丹参复方成分对一氧化氮合成阻滞孕鼠胎盘超微形态影响研究[J].中华现代中西医杂志,2005,3(2):516-518
[40]朴春梅.黄芪对糖尿病的药理机理研究近况[J].云南中医中药杂志,2005,26(2):54-55
[41]汪德清,沈文梅,田亚平,等.黄芪有效成分对氧自由基清除作用的研究[J].生物化学与生物物理进展,1996,23(3):260-262
[42]王建新,梅广林,胡卫东.黄芪在肝脏缺血—再灌注损伤中保护作用的研究[J].南通大学学报(医学版),2005:25(3):161-163
[43]裴林,刘唤荣,张少丹,等.黄芪对缺氧缺血性脑损伤幼鼠一氧化氮、丙二醛含量的影响[J].中国中西医结合急救杂志,2001,8(4):222-223
[44]刘玉莲、杨从忠.黄芪药理作用概述[J].综述报告,2004,13(10):79-80
[45]张建新.黄芪对小鼠免疫功能影响的研究[J].时珍国医国药,2000,11(6):488-449
[46]杨林辉,陈东风.TNF-a与非酒精性脂肪肝[J].现代医药卫生,2007,23(10):55-57
[47]艾正琳,陈东风.非酒精性脂肪肝与胰岛素抵抗[J].现代医药卫生,2005,21(1):33-35.
[48]尤鹏.非酒精脂肪肝炎发病机制的研究进展[J].北京大学学报,2003,5(2):97-99
[49]张瑞红,黄宇,张雯等振.抑制血清TNF-a对大鼠脂肪肝的影响的实验研究[J].临床和实验医学杂志,2006,5(8):1069-1071
[50]王广华.非酒精性脂肪肝发病机制研究进展[J].中国康复理论与实践,2004,10(4):243-244
[51]蔡葵,何玉怡.非酒精性脂肪肝与代谢性紊乱的关系[J].实用医技杂志,2006,13,(15):2636-2637
[1]袁红霞,陈艳春.黄芪的现代药理研究及其临床应用[J].山东中医药大学学报,2000,24(5):15-16
[2]朱兆洪,丁柱.黄芪对脑缺血缺氧的保护作用机制[J].吉林中医药,2005,25(8):61-62
[3]王志新,姚金凤,张瑞锋,等.黄芪对神经细胞缺氧缺血损伤的保护作用[J].河南大学学报(医学版),2005,24(3):61-62
[4]裴林,刘唤荣,张少丹,等.黄芪对缺氧缺血性脑损伤幼鼠一氧化氮、丙二醛含量的影响[J].中国中西医结合急救杂志,2001,8(4):222-223
[5]李论,柯俐,彭定凤.黄芪对心肌细胞缺氧时的作用研究[J].中西医结合心血管病杂志,2003,1(2):79-80
[6]石刚刚,陈锦香,李长潮,等.黄芪注射液对冠状动脉直接作用的研究[J].中药新药与临床药理,1999,10(1):38-39
[7]章辰芳,孔繁智,柴秀娟,等.黄芪生脉颗粒剂对小型猪实验性心肌缺血时的影响[J].中国实验方剂学杂志,1998,4(5):22-24
[8]颜光涛,郝秀,王录熳,等.失血性休克再灌注损伤血浆脂酶A2及其水解产物的变化[J].中国病理生理杂志,1998.14(4):414-415
[9]王建新,梅广林,胡卫东.黄芪在肝脏缺血—再灌注损伤中保护作用的研究[J].南通大学学报(医学版),2005:25(3):161-163
[10]蒋晓峰,吴毅泰,李江涛,等.黄芪对大鼠急性肾缺血再灌注损伤的保护作用[J]. 基础医学与临床基础医学与临床,2002,22(5):479-481
[11]王迎新,李华,陈敏珠.黄芪提取物的抗疲劳和耐缺氧作用[J].中国实用医药杂志,2007,2(9):43-44
[12]王戈博,施文芙,张海林,等.黄芪的抗缺氧效应及对血红蛋白含量和动物动脉血压的影响[J].甘肃高师学报,2002,7(5):48-49
[13]柳济成,安昌善,严春花,等.黄芪对低氧性肺动脉高压大鼠肺组织中超氧化物歧化酶、丙二醛的影响[J].延边大学学报,2002,5(2):42-44
[14]何建国,荆志成,顾晴,等.缺氧性肺动脉高压大鼠泡内肺动脉与右心室胶原蛋白表达及黄芪的干预作用[J].中华医学杂志,1999,79(9):654-656
[15]王若光,李春梅,尤昭玲,等.黄芪丹参复方成分对一氧化氮合成阻滞孕鼠胎盘超微形态影响研究[J].中华现代中西医杂志,2005,3(2):516-518
[16]王红光.清开灵和黄芪注射液治疗新生儿缺氧缺血性脑病[J].中国乡村医药杂志,2001,8(12):19-20
[17]张印,焦华梅,王发渭.补阳还五汤治疗心脑血管疾病的辨治分析[J].中国临床康复,2005,9(27):26-27
[18]朱晔,蒋屏.益气补肾活血法佐治小儿肾病综合征的临床观察[J].湖南中医药大学学报,2007,27(2):60-61
[19]潘永峰,李风皖.清开灵加黄芪治疗酒精性肝病的疗效分析[J].肝脏,2001,6,(2):141-142
[20]柏干苹,李廷谦.益气活血药对慢性缺氧大鼠肺血流动力学的影响[J].中国临床康复,2004,8(4):1710-1711