黄芪扶正汤对免疫功能的影响及其机制的初步研究
|
摘要
第一章:不同剂量黄芪扶正汤对免疫抑制小鼠的溶血素和IL-2的影响
目的:观察不同剂量的黄芪扶正汤对免疫抑制小鼠的免疫调节作用,寻找最佳的干预剂量。
方法:取昆明种小鼠60只,随机分为6组,A组为空白对照组、B组为模型对照组、C组为9g生药/kg组、D组为18g生药/kg组、E组为36g生药/kg组、F组为72g生药/kg组,每组10只小鼠。除空白对照组外,其余小鼠在给药后第8、10、12天,腹腔注射氢化可的松25mg/kg/d,造出免疫抑制的动物模型。空白对照组和模型对照组予以生理盐水灌胃,其余组用不同剂量的黄芪扶正汤水煮液进行灌胃14天,检测小鼠血清溶血素的生成和IL-2的含量。
结果:使用氢化可的松后,小鼠血清溶血素和IL-2的水平明显下降,与空白组比有统计学差异(P＜0.05)。药物组经黄芪扶正汤干预后,小鼠血清溶血素和IL-2水平在18g生药/kg的剂量开始升高,在36g生药/kg剂量时作用最强,差异有统计学意义(P＜0.05)。
结论:1、使用氢化可的松造模成功。
2、黄芪扶正汤的最佳干预剂量为36g生药/kg。
第二章:黄芪扶正汤对免疫抑制小鼠的免疫调节作用
目的:从不同方面观察黄芪扶正汤对免疫抑制小鼠的免疫调节作用。
方法:取昆明种小鼠40只,随机分为4组,分别为空白组、模型组、黄芪扶正汤组和与玉屏风散组。除空白对照组外,其余小鼠在给药后第8、10、12天,腹腔注射氢化可的松25mg/kg/d,造出免疫抑制模型,空白对照组腹腔注射等量生理盐水。药物组小鼠灌胃给药14天,空白及模型对照组予等量生理盐水灌胃14天。给药后第15天,取小鼠血液和脾脏进行相关指标检测。采用TUNEL法检测小鼠脾细胞凋亡;免疫组化检测小鼠脾脏免疫细胞Bcl-2与Bax蛋白的表达;测定小鼠血清溶血素生成;ELISA法测血清中INF-γ、IL-4水平;流式细胞术测小鼠外周血T细胞亚群;RT-PCR和Realtime PCR方法测小鼠脾细胞INF-γ、IL-4、T-bet和GATA-3 mRNA表达。
结果:1、模型组与空白组相比,脾细胞凋亡增多(P＜0.05),使用黄芪扶正汤和玉屏风散后凋亡减少,与模型组比有统计学意义,但组间也无差异。
2、模型组与空白组相比,脾脏Bcl-2阳性细胞减少Bax阳性细胞增多(P＜0.05),经黄芪扶正汤和玉屏风散干预后,Bcl-2增加Bax减少(P＜0.05),但组间也无差异。
3、模型组的血清溶血素低于空白组(P＜0.05),经黄芪扶正汤和玉屏风散干预后,溶血素较模型组明显升高(P＜0.05),但两组间差异无统计学意义。
4、模型组与空白组相比,血清INF-γ下降、IL-4升高,差异有统计学意义,经黄芪扶正汤和玉屏风散干预后,INF-γ明显升高、IL-4下降(P＜0.05),且黄芪扶正汤比玉屏风散的效果更明显(P＜0.05)。
5、模型组的CD3~+、CD4~+、CD8~+T细胞及CD4~+/CD8~+均明显低于空白组(P＜0.05),使用黄芪扶正汤或玉屏风散后上述指标均升高,差异有统计学意义,而黄芪扶正汤组比玉屏风散组升高更明显(P＜0.05)。
6、RT-PCR和实时荧光定量PCR结果均显示,模型组与空白组对比,细胞因子INF-γmRNA表达下降、IL-4 mRNA表达增加,同时转录因子T-bet mRNA表达下降而GATA-3 mRNA表达升高,差异有统计学意义。黄芪扶正汤和玉屏风散均能升高INF-γ和T-bet的mRNA表达,降低IL-4和GATA-3的mRNA表达,使T-bet/GATA-3比值更接近正常,且黄芪扶正汤效果更显著,差异有统计学意义。。
结论:1、黄芪扶正汤能提高免疫抑制小鼠的体液免疫功能,但与玉屏风散比无统计学差异。
2、黄芪扶正汤能提高免疫抑制小鼠的细胞免疫功能,平衡Th1/Th2细胞因子的比例,效果优于玉屏风散。
3、黄芪扶正汤调节Th1/Th2细胞因子比例的作用,可能部分源于对转录因子T-bet和GATA-3的mRNA表达的影响。
第三章黄芪扶正汤对老年人免疫功能的影响
目的:探讨黄芪扶正汤能否提高老年人的免疫和抗氧化功能。
资料与方法:选择无严重疾病、能生活自理的老年人(年龄＞60岁)60例,男女各半。随机分为中药组和西药组,中药组服用黄芪扶正汤剂300ml每天分两次服用。西药组肌注卡介菌多糖核酸注射液(Polysaccharide nucleic acid fraction of BCG,BCG-PSN),商品名斯奇康针1mg/次,每周2次。两组均用药4周。干预前后分别抽取两组观察对象的静脉血标本,检测相关免疫学指标。检测方法为:使用ELISA法测血清中IgG、INF-γ和IL-4浓度,流式细胞术测人外周血T细胞亚群和NK细胞数量,黄嘌呤氧化酶法测人血清超氧化物歧化酶(SOD),比色法测人血清总抗氧化能力硫代巴比妥酸比色法测人血清微量丙二醛(MDA)。
结果:1、斯奇康组研究对象失访率高于黄芪扶正汤组,差异有统计学意义。
2、干预后,黄芪扶正汤组老年人血清IgG水平提高,与治疗前相比有统计学差异(P＜0.05)。但与斯奇康组对比无统计学差异。
3、干预后,黄芪扶正汤组老年人血清INF-γ升高,IL-4下降,与治疗前相比均有统计学差异(P＜0.05)。但与斯奇康组对比无统计学差异。
4、干预后,黄芪扶正汤组老年人全血CD4~+/CD8~+T细胞升高,与治疗前相比有统计学差异(P＜0.05)。而且治疗前后的差值高于斯奇康组,差异有统计学意义(P＜0.05)。
5、干预后,黄芪扶正汤组全血CD56~+细胞数量升高,与治疗前相比有统计学差异(P＜0.05)。但与斯奇康组相比无差异。
6、干预后,黄芪扶正汤组研究对象的血清SOD和总抗氧化能力水平较治疗前提高,差异有统计学意义(P＜0.05)。而阳性对照组(斯奇康组)与治疗前相比无明显改变(P＞0.05)。两组间治疗前后差值比较,黄芪扶正汤组显著高于斯奇康组,差异有统计学意义(P＜0.05)。
7、干预后,黄芪扶正汤组研究对象的血清MDA水平较治疗降低,差异有统计学意义(P＜0.05)。而阳性对照组(斯奇康组)与治疗前相比血清MDA水平无明显改变(P＞0.05)。两组间治疗前后差值比较,黄芪扶正汤组显著高于斯奇康组,差异有统计学意义(P＜0.05)。
结论:1、黄芪扶正汤能提高老年人的细胞免疫和体液免疫功能,增加外周血NK细胞数量,效果与斯奇康注射液无差异。
2、黄芪扶正汤在调节Th1/Th2细胞因子的比例方面效果优于斯奇康注射液。
3、黄芪扶正汤能改善氧化应激状态,这可能是其改善免疫衰老的机制之一。
Chapter 1 Enhancement of immunity in the Immunosuppressive Mice by Different Dosage of Huangqi Fuzheng Tang
Objective:To study if Huangqi Fuzheng Tang could enhance the immunity in the immunosuppressive mice and find out the best dosage.
Methods:Sixty male Kunming mice were divided into 6 groups: normal control group,model group,9g/kg,18g/kg,36g/kg and 72g/kg Huangqi Fuzheng Tang treatment groups.Set up the immunosuppressive animal model by using hydrocortisone.Different dosages of Huangqi Fuzheng Tang apozema were given to the treatment groups by intragastric administration once daily for 14 days.The normal control group and the model group received the same volume of normal saline.The contents of serum hemolysin and IL-2 of the mice were measured.
Results:After giving hydrocortisone,compared to that of the normal control group,the serum hemolysin and IL-2 of the mice were decreased obviousely(P＜0.05).Huangqi Fuzheng Tang could elevate serum hemolysin and IL-2 when the dosages were 18g/kg,36g/kg and 72g/kg.The effect of 36g/kg was the strongest,the disparity had statistical significance.
Conclusion:1.The immunosuppressive mice model was set up successfully by giving hydrocortisone intraperitoneal injection.
2.The most effective dosage of Huangqi Fuzheng Tang was 36g/kg.
Chapter 2 Enhancement of Immunity in the Immunosuppressive Mice by Huangqi Fuzheng Tang
Objective:To study the enhancement of immunity in the immunosuppressive mice by using Huangqi Fuzheng Tang.
Methods:Forty mice were divided into 4 groups:normal control group,model group,Huangqi Fuzheng Tang(HFT) group and Yupingfeng San(YPF) group.Set up the immunosuppressive animal model by giving hydrocortisone intraperitoneal injection.Huangqi Fuzheng Tang and Yupingfeng San apozema were given to the mice of the treatment groups by intragastric administration once daily for 14 days.The normal control group and the model group received the same volume of normal saline. After 14 days the apoptosis of the spleen cells were assayed by using TUNEL staining.Bcl-2 and Bax proteins in the spleen were assayed by immunohistochemistry.The contents of hemolysin,IL-2、INF-γin the mice serum and the expression of CD3~+、CD4~+、CD8~+ in the peripheral blood lymphocytes were measured.RT-PCR and Realtime PCR were used to evaluate the mRNA of INF-γ、IL-4、T-bet and GATA-3 in the spleen cells.
Results:1.Compared to that of the normal control group,the apoptosis of the spleen cells in mice of the model group was increased significantly(P＜0.05).After treatment,the apoptosis of the spleen cells decreased significantly(P＜0.05),but there was no difference between HFT group and YPF group(P＞0.05).
2.The mice of the model group had less Bcl-2 positive cells and more Bax positive cells in the spleen than that of the normal group mice(P＜0.05).After treatment,Bcl-2 positive cells increased and Bax positive cells decreased in the mice of HFT group and YPF group(P＜0.05),but there was no statistical difference between the two groups.
3.The serum hemolysin in the mice of the model group were lower than that of the normal group mice(P＜0.05).After treatment,the serum hemolysin elevated obviously in the mice of the HFT group and YPF group,but there was no statistical difference between the two groups.
4.Compared to that of the normal control group,the model group had a lower level of serum INF-γ,but a higher level of serum IL-4(P＜0.05).Huangqi Fuzheng Tang could obviously elevate INF-γ,and descent IL-4,acted more effective than Yupingfeng San(P＜0.05).
5.Huangqi Fuzheng Tang could elevate the ratio of CD4~+/CD8~+T cells,and there was statistical difference between Huangqi Fuzheng Tang and Yupingfeng San(P＜0.05).
6.Both the RT-PCR and Realtime PCR revealed the Huangqi Fuzheng Tang could enhance the mRNA expression of INF-γ,and T-bet, but reduce the mRNA expression of IL-4 and GATA-3.And there was statistical difference between Huangqi Fuzheng Tang and Yupingfeng San.
Conclusion:1.Huangqi Fuzheng Tang could enhance the humoral immunity,but there was no statistical difference between the two.
2.Huangqi Fuzheng Tang could enhance the cellular immunity, balance the ratio of Th1/Th2 cytokines,and acted more effectively than Yupingfeng San in some aspects.
3.Huangqi Fuzheng Tang regulated the Th1/Th2 cytokines might through regulating the transcriptional factor T-bet and GATA-3.
Chapter 3 Immunomodulatory and Anti-oxidative Activity in the Elderly by Huangqi Fuzheng Tang
Objective:To investigate whether taking Huangqi Fuzheng Tang apozema daily could enhance immunity and have anti-oxidative effect in the elderly.
Methods:Sixty elderly(age＞60 years) volunteers participated in this program.They were divided randomly into two groups:Huangqi Fuzheng Tang(HFT) group and the Polysaccharide nucleic acid fraction of BCG(BCG-PSN) group.Volunteers in the HFT group took Huangqi Fuzheng Tang apozema 300ml/day,and the BCG-PSN group received BCG-PSN injection 1mg i.m twice a week.The treatment continued for 4weeks.Before and after the treatment the immunological parameters of the subjects' blood were examined.The parameters included serum IgG、INF-γand IL-4,expression of CD3~+、CD4~+、CD8~+、CD56~+in the peripheral blood lymphocytes.Serum concentration of SOD,total anti-oxidative capability and MDA were also measured.
Results:1.The rate of dropping out was higher in the BCG-PSN group than that of the HFT group(P＜0.05).
2.After the treatment,subjects'serum IgG elevated significantly in the HFT group than that before treatment(P＜0.05).But there were no statistical differences between the two groups.
3.After the treatment,subjects'serum INF-γincreased and IL-4 decreased significantly in the HFT group than that before treatment(P＜0.05).But there were no statistical differences between the two groups.
4.After the treatment,the ratio of CD4~+/CD8~+T cells of the elderly was higher than that before treatment(P＜0.05).And in HFT group that increased more obviously than that of BCG-PSN group(P＜0.05).
5.Huangqi Fuzhegn Tang could elevate the CD56~+ cells in the blood, statistically different from before the intervention.But there was no statistical difference between Huangqi Fuzheng Tang and BCG-PSN.
6.The levels of serum SOD and the total anti-oxidative capability in the HFT group increased significantly than that before the therapy(P＜0.05).But in the BCG-PSN group the levels of SOD and the total anti-oxidative capability were not changed before or after the treatment(P＞0.05).
7.The subjects'serum MDA were lower than that before in the HFT group(P＜0.05).But in the BCG-PSN group there were no differences before or after the treatment(P＞0.05).
Conclusion:1.Huangqi Fuzheng Tang could enhance the cellular immunity and the humoral immunity in the elderly,increase the amount of NK cells.
2.Huangqi Fuzheng Tang could balance the ratio of Th1/Th2 cytokines,and had a better effect than BCG-PSN.
3.Huangqi Fuzhegn Tang had anti-oxidative effect and improved the oxidative stress,that might be one of the anti-immunosenescence mechanisms.
目的:观察不同剂量的黄芪扶正汤对免疫抑制小鼠的免疫调节作用,寻找最佳的干预剂量。
方法:取昆明种小鼠60只,随机分为6组,A组为空白对照组、B组为模型对照组、C组为9g生药/kg组、D组为18g生药/kg组、E组为36g生药/kg组、F组为72g生药/kg组,每组10只小鼠。除空白对照组外,其余小鼠在给药后第8、10、12天,腹腔注射氢化可的松25mg/kg/d,造出免疫抑制的动物模型。空白对照组和模型对照组予以生理盐水灌胃,其余组用不同剂量的黄芪扶正汤水煮液进行灌胃14天,检测小鼠血清溶血素的生成和IL-2的含量。
结果:使用氢化可的松后,小鼠血清溶血素和IL-2的水平明显下降,与空白组比有统计学差异(P＜0.05)。药物组经黄芪扶正汤干预后,小鼠血清溶血素和IL-2水平在18g生药/kg的剂量开始升高,在36g生药/kg剂量时作用最强,差异有统计学意义(P＜0.05)。
结论:1、使用氢化可的松造模成功。
2、黄芪扶正汤的最佳干预剂量为36g生药/kg。
第二章:黄芪扶正汤对免疫抑制小鼠的免疫调节作用
目的:从不同方面观察黄芪扶正汤对免疫抑制小鼠的免疫调节作用。
方法:取昆明种小鼠40只,随机分为4组,分别为空白组、模型组、黄芪扶正汤组和与玉屏风散组。除空白对照组外,其余小鼠在给药后第8、10、12天,腹腔注射氢化可的松25mg/kg/d,造出免疫抑制模型,空白对照组腹腔注射等量生理盐水。药物组小鼠灌胃给药14天,空白及模型对照组予等量生理盐水灌胃14天。给药后第15天,取小鼠血液和脾脏进行相关指标检测。采用TUNEL法检测小鼠脾细胞凋亡;免疫组化检测小鼠脾脏免疫细胞Bcl-2与Bax蛋白的表达;测定小鼠血清溶血素生成;ELISA法测血清中INF-γ、IL-4水平;流式细胞术测小鼠外周血T细胞亚群;RT-PCR和Realtime PCR方法测小鼠脾细胞INF-γ、IL-4、T-bet和GATA-3 mRNA表达。
结果:1、模型组与空白组相比,脾细胞凋亡增多(P＜0.05),使用黄芪扶正汤和玉屏风散后凋亡减少,与模型组比有统计学意义,但组间也无差异。
2、模型组与空白组相比,脾脏Bcl-2阳性细胞减少Bax阳性细胞增多(P＜0.05),经黄芪扶正汤和玉屏风散干预后,Bcl-2增加Bax减少(P＜0.05),但组间也无差异。
3、模型组的血清溶血素低于空白组(P＜0.05),经黄芪扶正汤和玉屏风散干预后,溶血素较模型组明显升高(P＜0.05),但两组间差异无统计学意义。
4、模型组与空白组相比,血清INF-γ下降、IL-4升高,差异有统计学意义,经黄芪扶正汤和玉屏风散干预后,INF-γ明显升高、IL-4下降(P＜0.05),且黄芪扶正汤比玉屏风散的效果更明显(P＜0.05)。
5、模型组的CD3~+、CD4~+、CD8~+T细胞及CD4~+/CD8~+均明显低于空白组(P＜0.05),使用黄芪扶正汤或玉屏风散后上述指标均升高,差异有统计学意义,而黄芪扶正汤组比玉屏风散组升高更明显(P＜0.05)。
6、RT-PCR和实时荧光定量PCR结果均显示,模型组与空白组对比,细胞因子INF-γmRNA表达下降、IL-4 mRNA表达增加,同时转录因子T-bet mRNA表达下降而GATA-3 mRNA表达升高,差异有统计学意义。黄芪扶正汤和玉屏风散均能升高INF-γ和T-bet的mRNA表达,降低IL-4和GATA-3的mRNA表达,使T-bet/GATA-3比值更接近正常,且黄芪扶正汤效果更显著,差异有统计学意义。。
结论:1、黄芪扶正汤能提高免疫抑制小鼠的体液免疫功能,但与玉屏风散比无统计学差异。
2、黄芪扶正汤能提高免疫抑制小鼠的细胞免疫功能,平衡Th1/Th2细胞因子的比例,效果优于玉屏风散。
3、黄芪扶正汤调节Th1/Th2细胞因子比例的作用,可能部分源于对转录因子T-bet和GATA-3的mRNA表达的影响。
第三章黄芪扶正汤对老年人免疫功能的影响
目的:探讨黄芪扶正汤能否提高老年人的免疫和抗氧化功能。
资料与方法:选择无严重疾病、能生活自理的老年人(年龄＞60岁)60例,男女各半。随机分为中药组和西药组,中药组服用黄芪扶正汤剂300ml每天分两次服用。西药组肌注卡介菌多糖核酸注射液(Polysaccharide nucleic acid fraction of BCG,BCG-PSN),商品名斯奇康针1mg/次,每周2次。两组均用药4周。干预前后分别抽取两组观察对象的静脉血标本,检测相关免疫学指标。检测方法为:使用ELISA法测血清中IgG、INF-γ和IL-4浓度,流式细胞术测人外周血T细胞亚群和NK细胞数量,黄嘌呤氧化酶法测人血清超氧化物歧化酶(SOD),比色法测人血清总抗氧化能力硫代巴比妥酸比色法测人血清微量丙二醛(MDA)。
结果:1、斯奇康组研究对象失访率高于黄芪扶正汤组,差异有统计学意义。
2、干预后,黄芪扶正汤组老年人血清IgG水平提高,与治疗前相比有统计学差异(P＜0.05)。但与斯奇康组对比无统计学差异。
3、干预后,黄芪扶正汤组老年人血清INF-γ升高,IL-4下降,与治疗前相比均有统计学差异(P＜0.05)。但与斯奇康组对比无统计学差异。
4、干预后,黄芪扶正汤组老年人全血CD4~+/CD8~+T细胞升高,与治疗前相比有统计学差异(P＜0.05)。而且治疗前后的差值高于斯奇康组,差异有统计学意义(P＜0.05)。
5、干预后,黄芪扶正汤组全血CD56~+细胞数量升高,与治疗前相比有统计学差异(P＜0.05)。但与斯奇康组相比无差异。
6、干预后,黄芪扶正汤组研究对象的血清SOD和总抗氧化能力水平较治疗前提高,差异有统计学意义(P＜0.05)。而阳性对照组(斯奇康组)与治疗前相比无明显改变(P＞0.05)。两组间治疗前后差值比较,黄芪扶正汤组显著高于斯奇康组,差异有统计学意义(P＜0.05)。
7、干预后,黄芪扶正汤组研究对象的血清MDA水平较治疗降低,差异有统计学意义(P＜0.05)。而阳性对照组(斯奇康组)与治疗前相比血清MDA水平无明显改变(P＞0.05)。两组间治疗前后差值比较,黄芪扶正汤组显著高于斯奇康组,差异有统计学意义(P＜0.05)。
结论:1、黄芪扶正汤能提高老年人的细胞免疫和体液免疫功能,增加外周血NK细胞数量,效果与斯奇康注射液无差异。
2、黄芪扶正汤在调节Th1/Th2细胞因子的比例方面效果优于斯奇康注射液。
3、黄芪扶正汤能改善氧化应激状态,这可能是其改善免疫衰老的机制之一。
Chapter 1 Enhancement of immunity in the Immunosuppressive Mice by Different Dosage of Huangqi Fuzheng Tang
Objective:To study if Huangqi Fuzheng Tang could enhance the immunity in the immunosuppressive mice and find out the best dosage.
Methods:Sixty male Kunming mice were divided into 6 groups: normal control group,model group,9g/kg,18g/kg,36g/kg and 72g/kg Huangqi Fuzheng Tang treatment groups.Set up the immunosuppressive animal model by using hydrocortisone.Different dosages of Huangqi Fuzheng Tang apozema were given to the treatment groups by intragastric administration once daily for 14 days.The normal control group and the model group received the same volume of normal saline.The contents of serum hemolysin and IL-2 of the mice were measured.
Results:After giving hydrocortisone,compared to that of the normal control group,the serum hemolysin and IL-2 of the mice were decreased obviousely(P＜0.05).Huangqi Fuzheng Tang could elevate serum hemolysin and IL-2 when the dosages were 18g/kg,36g/kg and 72g/kg.The effect of 36g/kg was the strongest,the disparity had statistical significance.
Conclusion:1.The immunosuppressive mice model was set up successfully by giving hydrocortisone intraperitoneal injection.
2.The most effective dosage of Huangqi Fuzheng Tang was 36g/kg.
Chapter 2 Enhancement of Immunity in the Immunosuppressive Mice by Huangqi Fuzheng Tang
Objective:To study the enhancement of immunity in the immunosuppressive mice by using Huangqi Fuzheng Tang.
Methods:Forty mice were divided into 4 groups:normal control group,model group,Huangqi Fuzheng Tang(HFT) group and Yupingfeng San(YPF) group.Set up the immunosuppressive animal model by giving hydrocortisone intraperitoneal injection.Huangqi Fuzheng Tang and Yupingfeng San apozema were given to the mice of the treatment groups by intragastric administration once daily for 14 days.The normal control group and the model group received the same volume of normal saline. After 14 days the apoptosis of the spleen cells were assayed by using TUNEL staining.Bcl-2 and Bax proteins in the spleen were assayed by immunohistochemistry.The contents of hemolysin,IL-2、INF-γin the mice serum and the expression of CD3~+、CD4~+、CD8~+ in the peripheral blood lymphocytes were measured.RT-PCR and Realtime PCR were used to evaluate the mRNA of INF-γ、IL-4、T-bet and GATA-3 in the spleen cells.
Results:1.Compared to that of the normal control group,the apoptosis of the spleen cells in mice of the model group was increased significantly(P＜0.05).After treatment,the apoptosis of the spleen cells decreased significantly(P＜0.05),but there was no difference between HFT group and YPF group(P＞0.05).
2.The mice of the model group had less Bcl-2 positive cells and more Bax positive cells in the spleen than that of the normal group mice(P＜0.05).After treatment,Bcl-2 positive cells increased and Bax positive cells decreased in the mice of HFT group and YPF group(P＜0.05),but there was no statistical difference between the two groups.
3.The serum hemolysin in the mice of the model group were lower than that of the normal group mice(P＜0.05).After treatment,the serum hemolysin elevated obviously in the mice of the HFT group and YPF group,but there was no statistical difference between the two groups.
4.Compared to that of the normal control group,the model group had a lower level of serum INF-γ,but a higher level of serum IL-4(P＜0.05).Huangqi Fuzheng Tang could obviously elevate INF-γ,and descent IL-4,acted more effective than Yupingfeng San(P＜0.05).
5.Huangqi Fuzheng Tang could elevate the ratio of CD4~+/CD8~+T cells,and there was statistical difference between Huangqi Fuzheng Tang and Yupingfeng San(P＜0.05).
6.Both the RT-PCR and Realtime PCR revealed the Huangqi Fuzheng Tang could enhance the mRNA expression of INF-γ,and T-bet, but reduce the mRNA expression of IL-4 and GATA-3.And there was statistical difference between Huangqi Fuzheng Tang and Yupingfeng San.
Conclusion:1.Huangqi Fuzheng Tang could enhance the humoral immunity,but there was no statistical difference between the two.
2.Huangqi Fuzheng Tang could enhance the cellular immunity, balance the ratio of Th1/Th2 cytokines,and acted more effectively than Yupingfeng San in some aspects.
3.Huangqi Fuzheng Tang regulated the Th1/Th2 cytokines might through regulating the transcriptional factor T-bet and GATA-3.
Chapter 3 Immunomodulatory and Anti-oxidative Activity in the Elderly by Huangqi Fuzheng Tang
Objective:To investigate whether taking Huangqi Fuzheng Tang apozema daily could enhance immunity and have anti-oxidative effect in the elderly.
Methods:Sixty elderly(age＞60 years) volunteers participated in this program.They were divided randomly into two groups:Huangqi Fuzheng Tang(HFT) group and the Polysaccharide nucleic acid fraction of BCG(BCG-PSN) group.Volunteers in the HFT group took Huangqi Fuzheng Tang apozema 300ml/day,and the BCG-PSN group received BCG-PSN injection 1mg i.m twice a week.The treatment continued for 4weeks.Before and after the treatment the immunological parameters of the subjects' blood were examined.The parameters included serum IgG、INF-γand IL-4,expression of CD3~+、CD4~+、CD8~+、CD56~+in the peripheral blood lymphocytes.Serum concentration of SOD,total anti-oxidative capability and MDA were also measured.
Results:1.The rate of dropping out was higher in the BCG-PSN group than that of the HFT group(P＜0.05).
2.After the treatment,subjects'serum IgG elevated significantly in the HFT group than that before treatment(P＜0.05).But there were no statistical differences between the two groups.
3.After the treatment,subjects'serum INF-γincreased and IL-4 decreased significantly in the HFT group than that before treatment(P＜0.05).But there were no statistical differences between the two groups.
4.After the treatment,the ratio of CD4~+/CD8~+T cells of the elderly was higher than that before treatment(P＜0.05).And in HFT group that increased more obviously than that of BCG-PSN group(P＜0.05).
5.Huangqi Fuzhegn Tang could elevate the CD56~+ cells in the blood, statistically different from before the intervention.But there was no statistical difference between Huangqi Fuzheng Tang and BCG-PSN.
6.The levels of serum SOD and the total anti-oxidative capability in the HFT group increased significantly than that before the therapy(P＜0.05).But in the BCG-PSN group the levels of SOD and the total anti-oxidative capability were not changed before or after the treatment(P＞0.05).
7.The subjects'serum MDA were lower than that before in the HFT group(P＜0.05).But in the BCG-PSN group there were no differences before or after the treatment(P＞0.05).
Conclusion:1.Huangqi Fuzheng Tang could enhance the cellular immunity and the humoral immunity in the elderly,increase the amount of NK cells.
2.Huangqi Fuzheng Tang could balance the ratio of Th1/Th2 cytokines,and had a better effect than BCG-PSN.
3.Huangqi Fuzhegn Tang had anti-oxidative effect and improved the oxidative stress,that might be one of the anti-immunosenescence mechanisms.
引文
[1]Nestler G.Traditional Chinese medicine.Med Clin North Am,2002,86:63-73.
[2]Ikarashi Y,Yuzurihara M,Sakakibara I,et al.Effects of an oriental herbal medicine,"Saiboku-to",and its constituent herbs on Compound 48/80-induced histamine release from peritoneal mast cells in rats.Phytomedicine,2001,8:8-15.
[3]Li T,Tamada K,Abe K,et al.The restoration of the antitumor T cell response from stress-induced suppression using a traditional Chinese herbal medicine Hochu-ekki-to(TJ-41:Bu-Zhong-Yi-Qi-Tang).Immunopharmacology,1999,43:11-21.
[4]Ohtake N,Nakai Y,Yamamoto M,et al.The herbal medicine Shosaiko-to exerts different modulating effects on lung local immune responses among mouse strains.Int Immunopharmacol,2002,2:357-66.
[5]Sinclair S.Chinese herbs:a clinical review of Astragalus,Ligusticum,and Schizandrae.Altern Med Rev,1998,3:338-44.
[6]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算.中国临床药理学和治疗学,2004,9:1069-1072.
[7]任玮,左丽,钟志强.灵芝孢子粉对糖皮质激素抑制模型小鼠的免疫调节作用.中国免疫学杂志,2007,23:979-984.
[8]马玲,姚小曼.免疫失衡动物模型的复制及应用.中国食品卫生杂志,2000,12:44-46.
[9]张磊、吴瑕、王岚,等.玉屏风散多糖类成分对免疫功能的影响.中药药理与临床,2006,22:2-4.
[10]Boyaka PN,McGhee JR.Cytokines as adjuvants for the induction of mucosal immunity.Adv Drug Deliv Rev,2001,51:71-9.
[11]Clement-Kruzel S,Hwang SA,Kruzel MC,et al.Immune modulation of macrophage pro-inflammatory response by goldenseal and Astragalus extracts.J Med Food,2008,11:493-8.
[12]Block KI,Mead MN.Immune system effects of echinacea,ginseng,and astragalus:a review.Integr Cancer Ther,2003,2:247-67.
[13]Li J,Bao Y,Lam W,et al.Immunoregulatory and anti-tumor effects of polysaccharopeptide and Astragalus polysaccharides on tumor-bearing mice.Immunopharmacol Immunotoxicol,2008,30:771-82.
[14]Shao P,Zhao LH,Zhi-Chen,et al.Regulation on maturation and function of dendritic cells by Astragalus mongholicus polysaccharides.Int Immunopharmacol,2006,6:1161-6.
[15]Cho WC,Leung KN.In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus.J Ethnopharmacol JT - Journal of ethnopharmacology,2007,113:132-41.
[16]Gan L,Hua Zhang S,Liang Yang X,et al.Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum.Int Immunopharmacol,2004,4:563-9.
[17]Chen Z,Kwong Huat Tan B,Chan SH.Activation of T lymphocytes by polysaccharide-protein complex from Lycium barbarum L.Int Immunopharmacol,2008,8:1663-71.
[18]Du G,Liu L,Fang J.Experimental study on the enhancement of murine splenic lymphocyte proliferation by Lycium barbarum glycopeptide.J Huazhong Univ Sci Technolog Med Sci,2004,24:518-20,527.
[19]Zhu XL,Chen AF,Lin ZB.Ganoderma lucidum polysaccharides enhance the function of immunological effector cells in immunosuppressed mice.J Ethnopharmacol,2007,111:219-26.
[20]Lin ZB,Zhang HN.Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms.Acta Pharmacol Sin,2004,25:1387-95.
[21]Kuo MC,Weng CY,Ha CL,et al.Ganoderma lucidum mycelia enhance innate immunity by activating NF-kappaB.J Ethnopharmacol,2006,103:217-22.
[22]Cao QZ,Lin ZB.Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide.Acta Pharmacol Sin,2004,25:833-8.
[23]Lai CS,Yu MS,Yuen WH,et al.Antagonizing beta-amyloid peptide neurotoxicity of the anti-aging fungus Ganoderma lucidum.Brain Res,2008,1190:215-24.
[24]叶红翠,张小平,余红.多花黄精粗多糖抗肿瘤活性研究.中国实验方剂学杂志,2008.43-45.
[25]李璘,邱蓉丽,周长慧,等.女贞子多糖对荷瘤小鼠免疫功能的影响.南京中医药大学学报,2008,24:388-390.
[26]Marx J.How the glucocorticoids suppress immunity.Science JT- Science (New York,N.Y.),1995,270:232-3.
[27]Tsutsui S,Vergote D,Shariat N,et al.Glucocorticoids regulate innate immunity in a model of multiple sclerosis:reciprocal interactions between the A1 adenosine receptor and beta-arrestin-1 in monocytoid cells.FASEB J JT-The FASEB journal:official publication of the Federation of American Societies for Experimental Biology,2008,22:786-96.
[28]Zhang N,Truong-Tran QA,Tancowny B,et al.Glucocorticoids enhance or spare innate immunity:effects in airway epithelium are mediated by CCAAT/enhancer binding proteins.J Immunol JT - Journal of immunology (Baltimore,Md:1950),2007,179:578-89.
[29]Cohen IR,Stavy L,Feldman M.Glucocorticoids and cellular immunity in vitro.Facilitation of the sensitization phase and inhibition of the effector phase of a lymphocyte anti-fibroblast reaction.J Exp Med JT - The Journal of experimental medicine,1970,132:1055-70.
[30]Tanizaki Y,Kitani H,Mifune T,et al.Effects of glucocorticoids on humoral and cellular immunity and on airway inflammation in patients with steroid-dependent intractable asthma.J Asthma JT - The Journal of asthma:official journal of the Association for the Care of Asthma,1993,30:485-92.
[31]Knezevic D.[Suppression of tumor immunity by electromagnetic fields and glucocorticoids in mice with implanted Ehrlich carcinoma].Med Pregl JT-Medicinski pregled,2005,58:609-13.
[32]朱新华,后文俊,沈凌.实验性免疫抑制动物模型的稳定性探讨.云南大学学报(自然科学版),1998,20:142-144.
[33]Weiss A.Chapter 12:T lymphocyte activation.In:Paul WE,ed.Fundamental Immunology.Philadelphia(USA):Raven Publishers,1999.411-419.
[34]Schlatter J,Ortuno F,Cervera-Enguix S.Lymphocyte subsets and lymphokine production in patients with melancholic versus nonmelancholic depression.Psychiatry Res,2004,128:259-65.
[35]Wang M,Guilbert LJ,Li J,et al.A proprietary extract from North American ginseng(Panax quinquefolium) enhances IL-2 and IFN-gamma productions in murine spleen cells induced by Con-A.Int Immunopharmacol,2004,4:311-5.
[36]Bonafe M,Valensin S,Gianni W,et al.The unexpected contribution of immunosenescence to the leveling off of cancer incidence and mortality in the oldest old.Crit Rev Oncol Hematol,2001,39:227-33.
[37]Leonard W.Chapter 21:Type I cytokines and interferon and theirr eceptors.In:PaulWE,ed.Fundamentalimmunology.Philadelphia(USA):Raven Publishers, 1999.745-747.
[38]Calder PC.Immunological parameters:what do they mean?;Immunological parameters:what do they mean?.J Nutr,2007,137;137:773S-80S;773S-80S.
[39]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算.中国临床药理学和治疗学,2004.1069-1072.
[40]张磊、吴瑕、王岚,等.玉屏风散多糖类成分对免疫功能的影响.中药药理与临床,2006,22.
[41]国家药典委员会.中华人民共和国药典.北京:化学工业出版社,2005.409.
[42]Makino T.[Pharmacological properties of Gyokuheifusan,a traditional Kampo medicinal formula].Yakugaku Zasshi,2005,125:349-54.
[43]粟栗.玉屏风散中补气与解表药对小鼠细胞免疫功能的影响.吉林中医药,2008:46-49.
[44]徐启华,曾庆文,曹军.玉屏风散发酵液对小鼠腹腔巨噬细胞免疫功能影响的血清药理学研究 2005,225:79-81.中医药信息,2005,22:79-81.
[45]郑劼,洪敏,华永庆,等.玉屏风散对小鼠变应性接触性皮炎及脾淋巴细胞增殖的影响.中药药理与临床,2008.7-8.
[46]Zhang HJ,Tang XY,Ju BL,et al.[Effect of yupingfengsan on the growth of tumor and immunological function in tumor-bearing mice.].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2008,24:683-5.
[47]毕玉霞,刘诗柱.玉屏风散对小白鼠免疫功能影响的实验研究.中兽医医药杂志.2007:31-33.
[48]杨善浦,吴叶健,黄爱萍.反复呼吸道感染患儿T细胞亚群及免疫球蛋白变化的意义.山东医药,2007,47:83.
[49]张红军,张晓莉,宋宝辉.玉屏风散对小鼠红细胞免疫粘附功能及腹腔吞噬活性的影响.细胞与分子免疫学杂志,2006,19:619-621.
[50]Qiao J,Lin L,Tianhong W.[Progress in research on apoptosis in filamentous fungi--a review].Wei Sheng Wu Xue Bao,2008,48:551-5.
[51]Vicencio JM,Galluzzi L,Tajeddine N,et al.Senescence,apoptosis or autophagy? When a damaged cell must decide its path--a mini-review.Gerontology,2008,54:92-9.
[52]Weiss A.Chapter 12:T lymphocyte activation.In:Paul WE,ed.Fundamental Immunology.Philadelphia(USA):Raven Publishers,1999.532.
[53]Thompson EB.Stepping stones in the path of glucocorticoid-driven apoptosis of lymphoid cells.Acta Biochim Biophys Sin(Shanghai),2008,40:595-600.
[54]Okabe T,Takayanagi R,Yanase T.[The signaling mechanism of glucocorticoid-induced T-cell apoptosis].Nippon Rinsho,2008,66:94-7.
[55]Xu CJ,Chen KS,Ding H,et al.A review of methods for measuring plant programmed cell death(PCD).Yi Chuan,2004,26:127-32.
[56]Levine B,Sinha S,Kroemer G.Bcl-2 family members:dual regulators of apoptosis and autophagy.Autophagy,2008,4:600-6.
[57]Chai WS,Zhu XM,Li SH,et al.Role of Bcl-2 family members in caspase-3/9-dependent apoptosis during Pseudomonas aeruginosa infection in U937 cells.Apoptosis,2008,13:833-43.
[58]Vogel MW.Cell death,Bcl-2,Bax,and the cerebellum.Cerebellum,2002,1:277-87.
[59]Wu X,Deng Y.Bax and BH3-domain-only proteins in p53-mediated apoptosis.Front Biosci,2002,7:d151-6.
[60]Lalier L,Cartron PF,Juin P,et al.Bax activation and mitochondrial insertion during apoptosis.Apoptosis,2007,12:887-96.
[61]Salakou S,Kardamakis D,Tsamandas AC,et al.Increased Bax/Bcl-2 ratio up-regulates caspase-3 and increases apoptosis in the thymus of patients with myasthenia gravis.In Vivo,2007,21:123-32.
[62]Reagan-Shaw S,Nihal M,Ahsan H,et al.Combination of vitamin E and selenium causes an induction of apoptosis of human prostate cancer cells by enhancing Bax/Bcl-2 ratio.Prostate,2008,68:1624-34.
[63]Snyder JT,Alexander-Miller MA,Berzofskyl JA,et al.Molecular mechanisms and biological significance of CTL avidity.Curr HIV Res,2003,1:287-94.
[64]Liu CC,Huang KJ,Lin YS,et al.Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection.J Med Virol,2002,68:241-52.
[65]Mehrzad J,Zhao X.T lymphocyte proliferative capacity and CD4+/CD8+ ratio in primiparous and pluriparous lactating cows.J Dairy Res,2008,75:457-65.
[66]Koike M,Sekigawa I,Okada M,et al.Relationship between CD4(+)/CD8(+) T cell ratio and T cell activation in multiple myeloma:reference to IL-16.Leuk Res,2002,26:705-11.
[67]Kosonen J,Luhtala M,Viander M,et al.Candida albicans-specific lymphoproliferative and cytokine(IL-4 and IFN-gamma) responses in atopic eczema dermatitis syndrome.Evidence of CD4/CD8 and CD3/CD16+CD56 ratio elevations in vitro. Exp Dermatol, 2005,14:551-8.
[68] Pozzilli P, Visalli N, Cavallo MG, et al. Normalization of the CD4/CD8 lymphocyte ratio and increased B lymphocytes in long standing diabetic patients following therapy with thymopentin. Diabetes Res, 1987,6:51-6.
[69] Al-Sakkaf L, Pozzilli P, Tarn AC, et al. Persistent reduction of CD4/CD8 lymphocyte ratio and cell activation before the onset of type 1 (insulin-dependent) diabetes. Diabetologia, 1989,32:322-5.
[70] Maeda N, Sekigawa I, Iida N, et al. Relationship between CD4+/CD8+ T cell ratio and T cell activation in systemic lupus erythematosus. Scand J Rheumatol, 1999,28:166-70.
[71] Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nat Rev Immunol, 2002,2:933-44.
[72] Sun Q, Burton RL, Lucas KG. Cytokine production and cytolytic mechanism of CD4(+) cytotoxic T lymphocytes in ex vivo expanded therapeutic Epstein-Barr virus-specific T-cell cultures. Blood, 2002,99:3302-9.
[73] Bernabei P, Allione A, Rigamonti L, et al. Regulation of interferon-gamma receptor (INF-gammaR) chains: a peculiar way to rule the life and death of human lymphocytes. Eur Cytokine Netw, 2001,12:6-14.
[74] Li-Weber M, Krammer PH. Regulation of IL4 gene expression by T cells and therapeutic perspectives. Nat Rev Immunol, 2003,3:534-43.
[75] Nakamura T, Kamogawa Y, Bottomly K, et al. Polarization of IL-4- and IFN-gamma-producing CD4+ T cells following activation of naive CD4+ T cells. J Immunol, 1997,158:1085-94.
[76] Stanulis ED, Jordan SD, Rosecrans JA, et al. Disruption of Thl/Th2 cytokine balance by cocaine is mediated by corticosterone. Immunopharmacology, 1997,37:25-33.
[77] Mendoza L. A network model for the control of the differentiation process in Th cells. Biosystems, 2006,84:101-14.
[78] Kang H, Oh YJ, Choi HY, et al. Immunomodulatory effect of Schizonepeta tenuifolia water extract on mouse Thl/Th2 cytokine production in-vivo and in-vitro. J Pharm Pharmacol, 2008,60:901-7.
[79] Masubuchi Y, Sugiyama S, Horie T. Thl/Th2 cytokine balance as a determinant of acetaminophen-induced liver injury. Chem Biol Interact, 2008.
[80] Theodorou GL, Marousi S, Ellul J, et al. T helper 1 (Th1)/Th2 cytokine expression shift of peripheral blood CD4+ and CD8+ T cells in patients at the post-acute phase of stroke.Clin Exp Immunol,2008,152:456-63.
[81]Sui W,Tan J,Guo J,et al.An altered TH1/TH2 and pro-inflammatory cytokine profile in patients with end-stage renal disease detected by suspension array technology.Ren Fail,2009,31:1-5.
[82]Fang SP,Tanaka T,Tago F,et al.Immunomodulatory effects of gyokuheifusan on INF-gamma/IL-4(Th1/Th2) balance in ovalbumin(OVA)-induced asthma model mice.Biol Pharm Bull,2005,28:829-33.
[83]Glimcher LH,Murphy KM.Lineage commitment in the immune system:the T helper lymphocyte grows up.Genes Dev,2000,14:1693-711.
[84]Tan AH,Goh SY,Wong SC,et al.T helper cell-specific regulation of inducible costimulator expression via distinct mechanisms mediated by T-bet and GATA-3.J Biol Chem,2008,283:128-36.
[85]Usui T,Preiss JC,Kanno Y,et al.T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.J Exp Med,2006,203:755-66.
[86]Cen O,Ueda A,Guzman L,et al.The adaptor molecule signaling lymphocytic activation molecule-associated protein(SAP) regulates IFN-gamma and IL-4production in Valpha14 transgenic NKT cells via effects on GATA-3 and T-bet expression.J Immunol,2009,182:1370-8.
[87]Inman D,Kawana K,Schust D,et al.Cyclic regulation of T-Bet and GATA-3in human endometrium.Reprod Sci,2008,15:83-90.
[88]Chen GY,Osada H,Santamaria-Babi LF,et al.Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes.Proc Natl Acad Sci U S A,2006,103:16894-9.
[89]Chakir H,Wang H,Lefebvre DE,et al.T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations:predominant role of GATA-3.J Immunol Methods,2003,278:157-69.
[90]杨舒,钱会南.中医脾虚证的免疫机制研究进展.辽宁中医杂志,2008,35.1433-1435.
[91]Goodwin JS.Decreased immunity and increased morbidity in the elderly.Nutr Rev,1995,53:S41-4;discussion S44-6.
[92]Haynes L,Swain SL,Cambier J,et al.Aging and immune function.Summary of a workshop held at Trudeau Institute,Saranac Lake,NY.Mech Ageing Dev, 2005,126:822-5.
[93]Buford TW,Willoughby DS.Impact of DHEA(S) and cortisol on immune function in aging:a brief review.Appl Physiol Nutr Metab,2008,33:429-33.
[94]Solana R,Mariani E.NK and NK/T cells in human senescence.Vaccine,2000,18:1613-20.
[95]Wenisch C,Patruta S,Daxbock F,et al.Effect of age on human neutrophil function.J Leukoc Biol,2000,67:40-5.
[96]Butcher S,Chahel H,Lord JM.Review article:ageing and the neutrophil:no appetite for killing?.Immunology,2000,100:411-6.
[97]Bauer T,Weisser B.[Effect of aerobic endurance exercise on immune function in elderly athletes].Praxis(Bern 1994),2002,91:153-8.
[98]Wardwell L,Chapman-Novakofski K,Herrel S,et al.Nutrient intake and immune function of elderly subjects.J Am Diet Assoc,2008,108:2005-12.
[99]Haase H,Mocchegiani E,Rink L.Correlation between zinc status and immune function in the elderly.Biogerontology,2006,7:421-8.
[100]Chiang BL,Sheih YH,Wang LH,et al.Enhancing immunity by dietary consumption of a probiotic lactic acid bacterium(Bifidobacterium lactis HN019):optimization and definition of cellular immune responses.Eur J Clin Nutr,2000,54:849-55.
[101]宁云山,姜德建,刘珊珊.卡介苗及卡介菌多糖核酸提取物的免疫调节作用及临床应用.中国生物制品学杂志,2008.74-77.
[102]Panayi GS.Targetting of cells involved in the pathogenesis of rheumatoid arthritis.Rheumatology,1999.3-7.
[103]Breitbart E,Wang X,Leka LS,et al.Altered memory B-cell homeostasis in human aging.J Gerontol A Biol Sci Med Sci,2002,57:B304-11.
[104]Colonna-Romano G,Bulati M,Aquino A,et al.B cells in the aged:CD27,CD5,and CD40 expression.Mech Ageing Dev,2003,124:389-93.
[105]Krieg AM,Yi AK,Matson S,et al.CpG motifs in bacterial DNA trigger direct B-cell activation.Nature,1995,374:546-9.
[106]田德增,王升,张永选,等.卡介菌多糖核酸注射液对2型糖尿病患者免疫功能的调节.中国药房.122-123.
[107]Linton PJ,Haynes L,Tsui L,et al.From naive to effector--alterations with aging.Immunol Rev,1997,160:9-18.
[108]Ouyang Q,Wagner WM,Zheng W,et al.Dysfunctional CMV-specific CD8(+) T cells accumulate in the elderly. Exp Gerontol, 2004,39:607-13.
[109] Olsson J, Wikby A, Johansson B, et al. Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old:the Swedish longitudinal OCTO immune study. Mech Ageing Dev,2000,121:187-201.
[110] Bokhari SM, Kim KJ, Pinson DM, et al. NK cells and gamma interferon coordinate the formation and function of hepatic granulomas in mice infected with the Francisella tularensis live vaccine strain. Infect Immun,2008,76:1379-89.
[111] Mariani E, Meneghetti A, Neri S, et al. Chemokine production by natural killer cells from nonagenarians. Eur J Immunol, 2002,32:1524-9.
[112] Majumder B, Venkatachari NJ, O'Leary S, et al. Infection with Vpr-positive human immunodeficiency virus type 1 impairs NK cell function indirectly through cytokine dysregulation of infected target cells. J Virol,2008,82:7189-200.
[113] Pegram HJ, Jackson JT, Smyth MJ, et al. Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo. J Immunol, 2008,181:3449-55.
[114] Germain C, Campigna E, Salhi I, et al. Redirecting NK cells mediated tumor cell lysis by a new recombinant bifunctional protein. Protein Eng Des Sel,2008,21:665-72.
[115] Chiossone L, Vitale C, Cottalasso F, et al. Molecular analysis of the methylprednisolone-mediated inhibition of NK-cell function: evidence for different susceptibility of IL-2- versus IL-15-activated NK cells. Blood,2007,109:3767-75.
[116] Vitale C, Chiossone L, Morreale G, et al. Human natural killer cells undergoing in vivo differentiation after allogeneic bone marrow transplantation: analysis of the surface expression and function of activating NK receptors. Mol Immunol,2005,42:405-11.
[117] van den Biggelaar AH, Huizinga TW, de Craen AJ, et al. Impaired innate immunity predicts frailty in old age. The Leiden 85-plus study. Exp Gerontol, 2004,39:1407-14.
[118] Borrego F, Alonso MC, Galiani MD, et al. NK phenotypic markers and IL2 response in NK cells from elderly people. Exp Gerontol, 1999,34:253-65.
[119] Miyaji C, Watanabe H, Toma H, et al. Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians. Hum Immunol,2000,61:908-16.
[120] Forsey RJ, Thompson JM, Ernerudh J, et al. Plasma cytokine profiles in elderly humans. Mech Ageing Dev, 2003,124:487-93.
[121] Hallquist N, Hakki A, Wecker L, et al. Differential effects of nicotine and aging on splenocyte proliferation and the production of Th1- versus Th2-type cytokines. Proc Soc Exp Biol Med, 2000,224:141-6.
[122] Jankovic D, Sher A, Yap G. Thl/Th2 effector choice in parasitic infection: decision making by committee. Curr Opin Immunol, 2001,13:403-9.
[123] Shen HH, Zhang GS, Wang PL. Mycobacterium bovis-Bacillus Calmette-Guerin and asthma. Chin Med J (Engl), 2005,118:942-7.
[124] Solomon TP, Marchetti CM, Krishnan RK, et al. Effects of aging on basal fat oxidation in obese humans. Metabolism, 2008,57:1141-7.
[125] Viveros MP, Arranz L, Hernanz A, et al. A model of premature aging in mice based on altered stress-related behavioral response and immunosenescence.Neuroimmunomodulation, 2007,14:157-62.
[126] Kim HJ, Barajas B, Chan RC, et al. Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: implications for systemic disease and immunosenescence. J Allergy Clin Immunol, 2007,119:1225-33.
[127] Widmer R, Ziaja I, Grune T. Protein oxidation and degradation during aging: role in skin aging and neurodegeneration. Free Radic Res, 2006,40:1259-68.
[128] Koleva DI, Petrova VY, Kujumdzieva AV. Comparison of enzymatic antioxidant defence systems in different metabolic types of yeasts. Can J Microbiol, 2008,54:957-63.
[129] Braga PC, Dal Sasso M, Fonti E, et al. Antioxidant activity of bisabolol: inhibitory effects on chemiluminescence of human neutrophil bursts and cell-free systems. Pharmacology, 2009,83:110-5.
[130] Yalinkilic O, Enginar H. Effect of X-radiation on lipid peroxidation and antioxidant systems in rats treated with saponin-containing compounds. Photochem Photobiol, 2008,84:236-42.
[131] Jolitha AB, Subramanyam MV, Asha Devi S. Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain: studies on superoxide dismutase isoenzymes and protein oxidation status. Exp Gerontol, 2006,41:753-63.
[132] Cao HX, He LQ, Shen YJ. [Changes of SOD, GSH and MDA in renal tissues of diabetic hyperlipidemia rats]. Zhong Xi Yi Jie He Xue Bao, 2004,2:36-8.
[133] Voss P, Siems W. Clinical oxidation parameters of aging. Free Radic Res, 2006,40:1339-49.
[134] Stadtman ER. Protein oxidation and aging. Free Radic Res, 2006,40:1250-8.
[135] Nestler, G. Traditional Chinese medicine. Med. Clin. N. Am,2002. 1-9.
[136] Normile D. Asian medicine. The new face of traditional Chinese medicine.Science, 2003,299:188-90.
[137] Plaeger SF. Clinical immunology and traditional herbal medicines. Clin Diagn Lab Immunol, 2003,10:337-8.
[138] Liu S, Yi LZ, Liang YZ. Traditional Chinese medicine and separation science. J Sep Sci, 2008,31:2113-37.
[139] Weng XS. [Treatment of leucopenia with pure Astragalus preparation-an analysis of 115 leucopenic cases]. Zhongguo Zhong Xi Yi Jie He Za Zhi,1995,15:462-4.
[140] Mills S, Bone K. Principles and Practice of Phytotherapy. Edinburgh, Scotland: Churchill Livingstone, 2000:273-279.
[141] Jiao Y, Wen J, Yu X. Influence of flavonoid of Astragalus membranaceus's stem and leaves on the function of cell mediated immunity in mice. Zhongguo Zhong Xi Yi Jie He Za Zhi, 1999,19:356-358.
[142] Mao XJ. Effect of radix hedysari polysaccharide and Astragalus mongholicus polysaccharide on the humoral immunity of mice. Chin J Immunol, 1998.158-162.
[143] Zhao XZ. [Effects of Astragalus membranaceus and Tripterygium hypoglancum on natural killer cell activity of peripheral blood mononuclear in systemic lupus erythematosus]. Zhongguo Zhong Xi Yi Jie He Za Zhi,1992,12:669-71,645.
[144] Ling Weng, Yan Liu, Xue-ying Liu,et al. Effect of Astragalus polysaccharide injectable powder (APS-P) on cytokine secretion of murine splenocytes and NK activity of S-180-bearing mice. Study J Trad Chin Med,2003,21:1522-1524.
[145] Ma ZH, Zhang CY, Liu X, et al. Research on antitumor effect of Astragalus mongholicus polysaccharide to 6 kinds of tumor strain in mice. Acta Chin Med Pharmacol, 1996,4:55-56.
[146] Yoshida Y, Wang MQ, Liu JN, et al. Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in particular. Int J Immunopharmacol,1997,19:359-70.
[147] Bao X, Liu C, Fang J, et al. Structural and immunological studies of a major polysaccharide from spores of Ganoderma lucidum (Fr.) Karst. Carbohydr Res,2001,332:67-74.
[148] Bao XF, Wang XS, Dong Q, et al. Structural features of immunologically active polysaccharides from Ganoderma lucidum. Phytochemistry,2002,59:175-81.
[149] Lin YL, Lee SS, Hou SM, et al. Polysaccharide purified from Ganoderma lucidum induces gene expression changes in human dendritic cells and promotes T helper 1 immune response in BALB/c mice. Mol Pharmacol,2006,70:637-44.
[150] Kim HM, Han SB, Oh GT, et al. Stimulation of humoral and cell mediated immunity by polysaccharide from mushroom Phellinus linteus. Int J Immunopharmacol, 1996,18:295-303.
[151] Yin G, Ardo L, Thompson KD, et al. Chinese herbs (Astragalus radix and Ganoderma lucidum) enhance immune response of carp, Cyprinus carpio, and protection against Aeromonas hydrophila. Fish Shellfish Immunol,2009,26:140-5.
[152] Wang SY, Hsu ML, Hsu HC, et al. The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer, 1997,70:699-705.
[153] Gao Y, Tang W, Dai X, et al. Effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer.J Med Food, 2005,8:159-68.
[154] Gao Y, Zhou S, Jiang W, et al. Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest, 2003,32:201-15.
[155] Peng X, Tian G. Structural characterization of the glycan part of glycoconjugate LbGp2 from Lycium barbarum L. Carbohydr Res, 2001,331:95-9.
[156] Ha KT, Yoon SJ, Choi DY, et al. Protective effect of Lycium chinense fruit on carbon tetrachloride-induced hepatotoxicity.J Ethnopharmacol,2005,96:529-35.
[157]Luo Q,Cai Y,Yan J,et al.Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts from Lycium barbarum.Life Sci,2004,76:137-49.
[158]Li XM,Ma YL,Liu XJ.Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice.J Ethnopharmacol,2007,111:504-11.
[159]Luo Q,Yan J,Zhang S.[Effects of pure and crude Lycium barbarum polysaccharides on immunopharmacology].Zhong Yao Cai,1999,22:246-9.
[160]Zhu J,Zhao LH,Chen Z.[Stimulation by Lycium bararum polysaccharides of the maturation of dendritic cells in murine bone marrow].Zhejiang Da Xue Xue Bao Yi Xue Ban,2006,35:648-52.
[161]Gan L,Zhang SH,Liu Q,et al.A polysaccharide-protein complex from Lycium barbarum upregulates cytokine expression in human peripheral blood mononuclear cells.Eur J Pharmacol,2003,471:217-22.
[162]Li ML,Liu ML.[Analysis of trace elements in fructus Ligustri Lucidi and its processed products].Zhongguo Zhong Yao Za Zhi,1989,14:727-9,762.
[163]Hao Z,Hang B,Wang Y.[Hypoglycemic effect of fructus Ligustri Lucidi].Zhongguo Zhong Yao Za Zhi,1992,17:429-31,447.
[164]Zhang Y,Lai WP,Leung PC,et al.Improvement of Ca balance by Fructus Ligustri Lucidi extract in aged female rats.Osteoporos Int,2008,19:235-42.
[165]Zhang Y,Dong XL,Leung PC,et al.Fructus ligustri lucidi extract improves calcium balance and modulates the calciotropic hormone level and vitamin D-dependent gene expression in aged ovariectomized rats.Menopause,2008,15:558-65.
[166]He J,Li Y,Wei S,et al.[Effects of mixture of Astragalus membranaceus,Fructus Ligustri lucidi and Eclipta prostrata on immune function in mice].Hua Xi Yi Ke Da Xue Xue Bao,1992,23:408-11.
[167]Ruan H,Lu Z.[Studies on immunomodulatory function of polysaccharide of Fructus Ligustri Lucidi].Zhongguo Zhong Yao Za Zhi,1999,24:691-3,704.
[168]李璘,邱蓉丽,周长慧,等.女贞子多糖对荷瘤小鼠免疫功能的影响.南京中医药大学学报,2008,6.388-390.
[169]Li ML.[Progress in the study on fructus Ligustri lucidi].Zhongguo Zhong Yao Za Zhi,1994,19:504-6.
[170]Liu T,Zheng X,Yang X,et al.[Quantity study of cultivated and wild Rhizoma Polygonati Odorati].Zhong Yao Cai,2005,28:14-6.
[171]Chen H,Feng R,Guo Y,et al.Hypoglycemic effects of aqueous extract of Rhizoma Polygonati Odorati in mice and rats.J Ethnopharmacol,2001,74:225-9.
[172]叶红翠,张小平,余红,等.多花黄精粗多糖抗肿瘤活性研究.中国实验方剂学杂志,2008,14:43-45.
[2]Ikarashi Y,Yuzurihara M,Sakakibara I,et al.Effects of an oriental herbal medicine,"Saiboku-to",and its constituent herbs on Compound 48/80-induced histamine release from peritoneal mast cells in rats.Phytomedicine,2001,8:8-15.
[3]Li T,Tamada K,Abe K,et al.The restoration of the antitumor T cell response from stress-induced suppression using a traditional Chinese herbal medicine Hochu-ekki-to(TJ-41:Bu-Zhong-Yi-Qi-Tang).Immunopharmacology,1999,43:11-21.
[4]Ohtake N,Nakai Y,Yamamoto M,et al.The herbal medicine Shosaiko-to exerts different modulating effects on lung local immune responses among mouse strains.Int Immunopharmacol,2002,2:357-66.
[5]Sinclair S.Chinese herbs:a clinical review of Astragalus,Ligusticum,and Schizandrae.Altern Med Rev,1998,3:338-44.
[6]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算.中国临床药理学和治疗学,2004,9:1069-1072.
[7]任玮,左丽,钟志强.灵芝孢子粉对糖皮质激素抑制模型小鼠的免疫调节作用.中国免疫学杂志,2007,23:979-984.
[8]马玲,姚小曼.免疫失衡动物模型的复制及应用.中国食品卫生杂志,2000,12:44-46.
[9]张磊、吴瑕、王岚,等.玉屏风散多糖类成分对免疫功能的影响.中药药理与临床,2006,22:2-4.
[10]Boyaka PN,McGhee JR.Cytokines as adjuvants for the induction of mucosal immunity.Adv Drug Deliv Rev,2001,51:71-9.
[11]Clement-Kruzel S,Hwang SA,Kruzel MC,et al.Immune modulation of macrophage pro-inflammatory response by goldenseal and Astragalus extracts.J Med Food,2008,11:493-8.
[12]Block KI,Mead MN.Immune system effects of echinacea,ginseng,and astragalus:a review.Integr Cancer Ther,2003,2:247-67.
[13]Li J,Bao Y,Lam W,et al.Immunoregulatory and anti-tumor effects of polysaccharopeptide and Astragalus polysaccharides on tumor-bearing mice.Immunopharmacol Immunotoxicol,2008,30:771-82.
[14]Shao P,Zhao LH,Zhi-Chen,et al.Regulation on maturation and function of dendritic cells by Astragalus mongholicus polysaccharides.Int Immunopharmacol,2006,6:1161-6.
[15]Cho WC,Leung KN.In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus.J Ethnopharmacol JT - Journal of ethnopharmacology,2007,113:132-41.
[16]Gan L,Hua Zhang S,Liang Yang X,et al.Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum.Int Immunopharmacol,2004,4:563-9.
[17]Chen Z,Kwong Huat Tan B,Chan SH.Activation of T lymphocytes by polysaccharide-protein complex from Lycium barbarum L.Int Immunopharmacol,2008,8:1663-71.
[18]Du G,Liu L,Fang J.Experimental study on the enhancement of murine splenic lymphocyte proliferation by Lycium barbarum glycopeptide.J Huazhong Univ Sci Technolog Med Sci,2004,24:518-20,527.
[19]Zhu XL,Chen AF,Lin ZB.Ganoderma lucidum polysaccharides enhance the function of immunological effector cells in immunosuppressed mice.J Ethnopharmacol,2007,111:219-26.
[20]Lin ZB,Zhang HN.Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms.Acta Pharmacol Sin,2004,25:1387-95.
[21]Kuo MC,Weng CY,Ha CL,et al.Ganoderma lucidum mycelia enhance innate immunity by activating NF-kappaB.J Ethnopharmacol,2006,103:217-22.
[22]Cao QZ,Lin ZB.Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide.Acta Pharmacol Sin,2004,25:833-8.
[23]Lai CS,Yu MS,Yuen WH,et al.Antagonizing beta-amyloid peptide neurotoxicity of the anti-aging fungus Ganoderma lucidum.Brain Res,2008,1190:215-24.
[24]叶红翠,张小平,余红.多花黄精粗多糖抗肿瘤活性研究.中国实验方剂学杂志,2008.43-45.
[25]李璘,邱蓉丽,周长慧,等.女贞子多糖对荷瘤小鼠免疫功能的影响.南京中医药大学学报,2008,24:388-390.
[26]Marx J.How the glucocorticoids suppress immunity.Science JT- Science (New York,N.Y.),1995,270:232-3.
[27]Tsutsui S,Vergote D,Shariat N,et al.Glucocorticoids regulate innate immunity in a model of multiple sclerosis:reciprocal interactions between the A1 adenosine receptor and beta-arrestin-1 in monocytoid cells.FASEB J JT-The FASEB journal:official publication of the Federation of American Societies for Experimental Biology,2008,22:786-96.
[28]Zhang N,Truong-Tran QA,Tancowny B,et al.Glucocorticoids enhance or spare innate immunity:effects in airway epithelium are mediated by CCAAT/enhancer binding proteins.J Immunol JT - Journal of immunology (Baltimore,Md:1950),2007,179:578-89.
[29]Cohen IR,Stavy L,Feldman M.Glucocorticoids and cellular immunity in vitro.Facilitation of the sensitization phase and inhibition of the effector phase of a lymphocyte anti-fibroblast reaction.J Exp Med JT - The Journal of experimental medicine,1970,132:1055-70.
[30]Tanizaki Y,Kitani H,Mifune T,et al.Effects of glucocorticoids on humoral and cellular immunity and on airway inflammation in patients with steroid-dependent intractable asthma.J Asthma JT - The Journal of asthma:official journal of the Association for the Care of Asthma,1993,30:485-92.
[31]Knezevic D.[Suppression of tumor immunity by electromagnetic fields and glucocorticoids in mice with implanted Ehrlich carcinoma].Med Pregl JT-Medicinski pregled,2005,58:609-13.
[32]朱新华,后文俊,沈凌.实验性免疫抑制动物模型的稳定性探讨.云南大学学报(自然科学版),1998,20:142-144.
[33]Weiss A.Chapter 12:T lymphocyte activation.In:Paul WE,ed.Fundamental Immunology.Philadelphia(USA):Raven Publishers,1999.411-419.
[34]Schlatter J,Ortuno F,Cervera-Enguix S.Lymphocyte subsets and lymphokine production in patients with melancholic versus nonmelancholic depression.Psychiatry Res,2004,128:259-65.
[35]Wang M,Guilbert LJ,Li J,et al.A proprietary extract from North American ginseng(Panax quinquefolium) enhances IL-2 and IFN-gamma productions in murine spleen cells induced by Con-A.Int Immunopharmacol,2004,4:311-5.
[36]Bonafe M,Valensin S,Gianni W,et al.The unexpected contribution of immunosenescence to the leveling off of cancer incidence and mortality in the oldest old.Crit Rev Oncol Hematol,2001,39:227-33.
[37]Leonard W.Chapter 21:Type I cytokines and interferon and theirr eceptors.In:PaulWE,ed.Fundamentalimmunology.Philadelphia(USA):Raven Publishers, 1999.745-747.
[38]Calder PC.Immunological parameters:what do they mean?;Immunological parameters:what do they mean?.J Nutr,2007,137;137:773S-80S;773S-80S.
[39]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算.中国临床药理学和治疗学,2004.1069-1072.
[40]张磊、吴瑕、王岚,等.玉屏风散多糖类成分对免疫功能的影响.中药药理与临床,2006,22.
[41]国家药典委员会.中华人民共和国药典.北京:化学工业出版社,2005.409.
[42]Makino T.[Pharmacological properties of Gyokuheifusan,a traditional Kampo medicinal formula].Yakugaku Zasshi,2005,125:349-54.
[43]粟栗.玉屏风散中补气与解表药对小鼠细胞免疫功能的影响.吉林中医药,2008:46-49.
[44]徐启华,曾庆文,曹军.玉屏风散发酵液对小鼠腹腔巨噬细胞免疫功能影响的血清药理学研究 2005,225:79-81.中医药信息,2005,22:79-81.
[45]郑劼,洪敏,华永庆,等.玉屏风散对小鼠变应性接触性皮炎及脾淋巴细胞增殖的影响.中药药理与临床,2008.7-8.
[46]Zhang HJ,Tang XY,Ju BL,et al.[Effect of yupingfengsan on the growth of tumor and immunological function in tumor-bearing mice.].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2008,24:683-5.
[47]毕玉霞,刘诗柱.玉屏风散对小白鼠免疫功能影响的实验研究.中兽医医药杂志.2007:31-33.
[48]杨善浦,吴叶健,黄爱萍.反复呼吸道感染患儿T细胞亚群及免疫球蛋白变化的意义.山东医药,2007,47:83.
[49]张红军,张晓莉,宋宝辉.玉屏风散对小鼠红细胞免疫粘附功能及腹腔吞噬活性的影响.细胞与分子免疫学杂志,2006,19:619-621.
[50]Qiao J,Lin L,Tianhong W.[Progress in research on apoptosis in filamentous fungi--a review].Wei Sheng Wu Xue Bao,2008,48:551-5.
[51]Vicencio JM,Galluzzi L,Tajeddine N,et al.Senescence,apoptosis or autophagy? When a damaged cell must decide its path--a mini-review.Gerontology,2008,54:92-9.
[52]Weiss A.Chapter 12:T lymphocyte activation.In:Paul WE,ed.Fundamental Immunology.Philadelphia(USA):Raven Publishers,1999.532.
[53]Thompson EB.Stepping stones in the path of glucocorticoid-driven apoptosis of lymphoid cells.Acta Biochim Biophys Sin(Shanghai),2008,40:595-600.
[54]Okabe T,Takayanagi R,Yanase T.[The signaling mechanism of glucocorticoid-induced T-cell apoptosis].Nippon Rinsho,2008,66:94-7.
[55]Xu CJ,Chen KS,Ding H,et al.A review of methods for measuring plant programmed cell death(PCD).Yi Chuan,2004,26:127-32.
[56]Levine B,Sinha S,Kroemer G.Bcl-2 family members:dual regulators of apoptosis and autophagy.Autophagy,2008,4:600-6.
[57]Chai WS,Zhu XM,Li SH,et al.Role of Bcl-2 family members in caspase-3/9-dependent apoptosis during Pseudomonas aeruginosa infection in U937 cells.Apoptosis,2008,13:833-43.
[58]Vogel MW.Cell death,Bcl-2,Bax,and the cerebellum.Cerebellum,2002,1:277-87.
[59]Wu X,Deng Y.Bax and BH3-domain-only proteins in p53-mediated apoptosis.Front Biosci,2002,7:d151-6.
[60]Lalier L,Cartron PF,Juin P,et al.Bax activation and mitochondrial insertion during apoptosis.Apoptosis,2007,12:887-96.
[61]Salakou S,Kardamakis D,Tsamandas AC,et al.Increased Bax/Bcl-2 ratio up-regulates caspase-3 and increases apoptosis in the thymus of patients with myasthenia gravis.In Vivo,2007,21:123-32.
[62]Reagan-Shaw S,Nihal M,Ahsan H,et al.Combination of vitamin E and selenium causes an induction of apoptosis of human prostate cancer cells by enhancing Bax/Bcl-2 ratio.Prostate,2008,68:1624-34.
[63]Snyder JT,Alexander-Miller MA,Berzofskyl JA,et al.Molecular mechanisms and biological significance of CTL avidity.Curr HIV Res,2003,1:287-94.
[64]Liu CC,Huang KJ,Lin YS,et al.Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection.J Med Virol,2002,68:241-52.
[65]Mehrzad J,Zhao X.T lymphocyte proliferative capacity and CD4+/CD8+ ratio in primiparous and pluriparous lactating cows.J Dairy Res,2008,75:457-65.
[66]Koike M,Sekigawa I,Okada M,et al.Relationship between CD4(+)/CD8(+) T cell ratio and T cell activation in multiple myeloma:reference to IL-16.Leuk Res,2002,26:705-11.
[67]Kosonen J,Luhtala M,Viander M,et al.Candida albicans-specific lymphoproliferative and cytokine(IL-4 and IFN-gamma) responses in atopic eczema dermatitis syndrome.Evidence of CD4/CD8 and CD3/CD16+CD56 ratio elevations in vitro. Exp Dermatol, 2005,14:551-8.
[68] Pozzilli P, Visalli N, Cavallo MG, et al. Normalization of the CD4/CD8 lymphocyte ratio and increased B lymphocytes in long standing diabetic patients following therapy with thymopentin. Diabetes Res, 1987,6:51-6.
[69] Al-Sakkaf L, Pozzilli P, Tarn AC, et al. Persistent reduction of CD4/CD8 lymphocyte ratio and cell activation before the onset of type 1 (insulin-dependent) diabetes. Diabetologia, 1989,32:322-5.
[70] Maeda N, Sekigawa I, Iida N, et al. Relationship between CD4+/CD8+ T cell ratio and T cell activation in systemic lupus erythematosus. Scand J Rheumatol, 1999,28:166-70.
[71] Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nat Rev Immunol, 2002,2:933-44.
[72] Sun Q, Burton RL, Lucas KG. Cytokine production and cytolytic mechanism of CD4(+) cytotoxic T lymphocytes in ex vivo expanded therapeutic Epstein-Barr virus-specific T-cell cultures. Blood, 2002,99:3302-9.
[73] Bernabei P, Allione A, Rigamonti L, et al. Regulation of interferon-gamma receptor (INF-gammaR) chains: a peculiar way to rule the life and death of human lymphocytes. Eur Cytokine Netw, 2001,12:6-14.
[74] Li-Weber M, Krammer PH. Regulation of IL4 gene expression by T cells and therapeutic perspectives. Nat Rev Immunol, 2003,3:534-43.
[75] Nakamura T, Kamogawa Y, Bottomly K, et al. Polarization of IL-4- and IFN-gamma-producing CD4+ T cells following activation of naive CD4+ T cells. J Immunol, 1997,158:1085-94.
[76] Stanulis ED, Jordan SD, Rosecrans JA, et al. Disruption of Thl/Th2 cytokine balance by cocaine is mediated by corticosterone. Immunopharmacology, 1997,37:25-33.
[77] Mendoza L. A network model for the control of the differentiation process in Th cells. Biosystems, 2006,84:101-14.
[78] Kang H, Oh YJ, Choi HY, et al. Immunomodulatory effect of Schizonepeta tenuifolia water extract on mouse Thl/Th2 cytokine production in-vivo and in-vitro. J Pharm Pharmacol, 2008,60:901-7.
[79] Masubuchi Y, Sugiyama S, Horie T. Thl/Th2 cytokine balance as a determinant of acetaminophen-induced liver injury. Chem Biol Interact, 2008.
[80] Theodorou GL, Marousi S, Ellul J, et al. T helper 1 (Th1)/Th2 cytokine expression shift of peripheral blood CD4+ and CD8+ T cells in patients at the post-acute phase of stroke.Clin Exp Immunol,2008,152:456-63.
[81]Sui W,Tan J,Guo J,et al.An altered TH1/TH2 and pro-inflammatory cytokine profile in patients with end-stage renal disease detected by suspension array technology.Ren Fail,2009,31:1-5.
[82]Fang SP,Tanaka T,Tago F,et al.Immunomodulatory effects of gyokuheifusan on INF-gamma/IL-4(Th1/Th2) balance in ovalbumin(OVA)-induced asthma model mice.Biol Pharm Bull,2005,28:829-33.
[83]Glimcher LH,Murphy KM.Lineage commitment in the immune system:the T helper lymphocyte grows up.Genes Dev,2000,14:1693-711.
[84]Tan AH,Goh SY,Wong SC,et al.T helper cell-specific regulation of inducible costimulator expression via distinct mechanisms mediated by T-bet and GATA-3.J Biol Chem,2008,283:128-36.
[85]Usui T,Preiss JC,Kanno Y,et al.T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.J Exp Med,2006,203:755-66.
[86]Cen O,Ueda A,Guzman L,et al.The adaptor molecule signaling lymphocytic activation molecule-associated protein(SAP) regulates IFN-gamma and IL-4production in Valpha14 transgenic NKT cells via effects on GATA-3 and T-bet expression.J Immunol,2009,182:1370-8.
[87]Inman D,Kawana K,Schust D,et al.Cyclic regulation of T-Bet and GATA-3in human endometrium.Reprod Sci,2008,15:83-90.
[88]Chen GY,Osada H,Santamaria-Babi LF,et al.Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes.Proc Natl Acad Sci U S A,2006,103:16894-9.
[89]Chakir H,Wang H,Lefebvre DE,et al.T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations:predominant role of GATA-3.J Immunol Methods,2003,278:157-69.
[90]杨舒,钱会南.中医脾虚证的免疫机制研究进展.辽宁中医杂志,2008,35.1433-1435.
[91]Goodwin JS.Decreased immunity and increased morbidity in the elderly.Nutr Rev,1995,53:S41-4;discussion S44-6.
[92]Haynes L,Swain SL,Cambier J,et al.Aging and immune function.Summary of a workshop held at Trudeau Institute,Saranac Lake,NY.Mech Ageing Dev, 2005,126:822-5.
[93]Buford TW,Willoughby DS.Impact of DHEA(S) and cortisol on immune function in aging:a brief review.Appl Physiol Nutr Metab,2008,33:429-33.
[94]Solana R,Mariani E.NK and NK/T cells in human senescence.Vaccine,2000,18:1613-20.
[95]Wenisch C,Patruta S,Daxbock F,et al.Effect of age on human neutrophil function.J Leukoc Biol,2000,67:40-5.
[96]Butcher S,Chahel H,Lord JM.Review article:ageing and the neutrophil:no appetite for killing?.Immunology,2000,100:411-6.
[97]Bauer T,Weisser B.[Effect of aerobic endurance exercise on immune function in elderly athletes].Praxis(Bern 1994),2002,91:153-8.
[98]Wardwell L,Chapman-Novakofski K,Herrel S,et al.Nutrient intake and immune function of elderly subjects.J Am Diet Assoc,2008,108:2005-12.
[99]Haase H,Mocchegiani E,Rink L.Correlation between zinc status and immune function in the elderly.Biogerontology,2006,7:421-8.
[100]Chiang BL,Sheih YH,Wang LH,et al.Enhancing immunity by dietary consumption of a probiotic lactic acid bacterium(Bifidobacterium lactis HN019):optimization and definition of cellular immune responses.Eur J Clin Nutr,2000,54:849-55.
[101]宁云山,姜德建,刘珊珊.卡介苗及卡介菌多糖核酸提取物的免疫调节作用及临床应用.中国生物制品学杂志,2008.74-77.
[102]Panayi GS.Targetting of cells involved in the pathogenesis of rheumatoid arthritis.Rheumatology,1999.3-7.
[103]Breitbart E,Wang X,Leka LS,et al.Altered memory B-cell homeostasis in human aging.J Gerontol A Biol Sci Med Sci,2002,57:B304-11.
[104]Colonna-Romano G,Bulati M,Aquino A,et al.B cells in the aged:CD27,CD5,and CD40 expression.Mech Ageing Dev,2003,124:389-93.
[105]Krieg AM,Yi AK,Matson S,et al.CpG motifs in bacterial DNA trigger direct B-cell activation.Nature,1995,374:546-9.
[106]田德增,王升,张永选,等.卡介菌多糖核酸注射液对2型糖尿病患者免疫功能的调节.中国药房.122-123.
[107]Linton PJ,Haynes L,Tsui L,et al.From naive to effector--alterations with aging.Immunol Rev,1997,160:9-18.
[108]Ouyang Q,Wagner WM,Zheng W,et al.Dysfunctional CMV-specific CD8(+) T cells accumulate in the elderly. Exp Gerontol, 2004,39:607-13.
[109] Olsson J, Wikby A, Johansson B, et al. Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old:the Swedish longitudinal OCTO immune study. Mech Ageing Dev,2000,121:187-201.
[110] Bokhari SM, Kim KJ, Pinson DM, et al. NK cells and gamma interferon coordinate the formation and function of hepatic granulomas in mice infected with the Francisella tularensis live vaccine strain. Infect Immun,2008,76:1379-89.
[111] Mariani E, Meneghetti A, Neri S, et al. Chemokine production by natural killer cells from nonagenarians. Eur J Immunol, 2002,32:1524-9.
[112] Majumder B, Venkatachari NJ, O'Leary S, et al. Infection with Vpr-positive human immunodeficiency virus type 1 impairs NK cell function indirectly through cytokine dysregulation of infected target cells. J Virol,2008,82:7189-200.
[113] Pegram HJ, Jackson JT, Smyth MJ, et al. Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo. J Immunol, 2008,181:3449-55.
[114] Germain C, Campigna E, Salhi I, et al. Redirecting NK cells mediated tumor cell lysis by a new recombinant bifunctional protein. Protein Eng Des Sel,2008,21:665-72.
[115] Chiossone L, Vitale C, Cottalasso F, et al. Molecular analysis of the methylprednisolone-mediated inhibition of NK-cell function: evidence for different susceptibility of IL-2- versus IL-15-activated NK cells. Blood,2007,109:3767-75.
[116] Vitale C, Chiossone L, Morreale G, et al. Human natural killer cells undergoing in vivo differentiation after allogeneic bone marrow transplantation: analysis of the surface expression and function of activating NK receptors. Mol Immunol,2005,42:405-11.
[117] van den Biggelaar AH, Huizinga TW, de Craen AJ, et al. Impaired innate immunity predicts frailty in old age. The Leiden 85-plus study. Exp Gerontol, 2004,39:1407-14.
[118] Borrego F, Alonso MC, Galiani MD, et al. NK phenotypic markers and IL2 response in NK cells from elderly people. Exp Gerontol, 1999,34:253-65.
[119] Miyaji C, Watanabe H, Toma H, et al. Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians. Hum Immunol,2000,61:908-16.
[120] Forsey RJ, Thompson JM, Ernerudh J, et al. Plasma cytokine profiles in elderly humans. Mech Ageing Dev, 2003,124:487-93.
[121] Hallquist N, Hakki A, Wecker L, et al. Differential effects of nicotine and aging on splenocyte proliferation and the production of Th1- versus Th2-type cytokines. Proc Soc Exp Biol Med, 2000,224:141-6.
[122] Jankovic D, Sher A, Yap G. Thl/Th2 effector choice in parasitic infection: decision making by committee. Curr Opin Immunol, 2001,13:403-9.
[123] Shen HH, Zhang GS, Wang PL. Mycobacterium bovis-Bacillus Calmette-Guerin and asthma. Chin Med J (Engl), 2005,118:942-7.
[124] Solomon TP, Marchetti CM, Krishnan RK, et al. Effects of aging on basal fat oxidation in obese humans. Metabolism, 2008,57:1141-7.
[125] Viveros MP, Arranz L, Hernanz A, et al. A model of premature aging in mice based on altered stress-related behavioral response and immunosenescence.Neuroimmunomodulation, 2007,14:157-62.
[126] Kim HJ, Barajas B, Chan RC, et al. Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: implications for systemic disease and immunosenescence. J Allergy Clin Immunol, 2007,119:1225-33.
[127] Widmer R, Ziaja I, Grune T. Protein oxidation and degradation during aging: role in skin aging and neurodegeneration. Free Radic Res, 2006,40:1259-68.
[128] Koleva DI, Petrova VY, Kujumdzieva AV. Comparison of enzymatic antioxidant defence systems in different metabolic types of yeasts. Can J Microbiol, 2008,54:957-63.
[129] Braga PC, Dal Sasso M, Fonti E, et al. Antioxidant activity of bisabolol: inhibitory effects on chemiluminescence of human neutrophil bursts and cell-free systems. Pharmacology, 2009,83:110-5.
[130] Yalinkilic O, Enginar H. Effect of X-radiation on lipid peroxidation and antioxidant systems in rats treated with saponin-containing compounds. Photochem Photobiol, 2008,84:236-42.
[131] Jolitha AB, Subramanyam MV, Asha Devi S. Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain: studies on superoxide dismutase isoenzymes and protein oxidation status. Exp Gerontol, 2006,41:753-63.
[132] Cao HX, He LQ, Shen YJ. [Changes of SOD, GSH and MDA in renal tissues of diabetic hyperlipidemia rats]. Zhong Xi Yi Jie He Xue Bao, 2004,2:36-8.
[133] Voss P, Siems W. Clinical oxidation parameters of aging. Free Radic Res, 2006,40:1339-49.
[134] Stadtman ER. Protein oxidation and aging. Free Radic Res, 2006,40:1250-8.
[135] Nestler, G. Traditional Chinese medicine. Med. Clin. N. Am,2002. 1-9.
[136] Normile D. Asian medicine. The new face of traditional Chinese medicine.Science, 2003,299:188-90.
[137] Plaeger SF. Clinical immunology and traditional herbal medicines. Clin Diagn Lab Immunol, 2003,10:337-8.
[138] Liu S, Yi LZ, Liang YZ. Traditional Chinese medicine and separation science. J Sep Sci, 2008,31:2113-37.
[139] Weng XS. [Treatment of leucopenia with pure Astragalus preparation-an analysis of 115 leucopenic cases]. Zhongguo Zhong Xi Yi Jie He Za Zhi,1995,15:462-4.
[140] Mills S, Bone K. Principles and Practice of Phytotherapy. Edinburgh, Scotland: Churchill Livingstone, 2000:273-279.
[141] Jiao Y, Wen J, Yu X. Influence of flavonoid of Astragalus membranaceus's stem and leaves on the function of cell mediated immunity in mice. Zhongguo Zhong Xi Yi Jie He Za Zhi, 1999,19:356-358.
[142] Mao XJ. Effect of radix hedysari polysaccharide and Astragalus mongholicus polysaccharide on the humoral immunity of mice. Chin J Immunol, 1998.158-162.
[143] Zhao XZ. [Effects of Astragalus membranaceus and Tripterygium hypoglancum on natural killer cell activity of peripheral blood mononuclear in systemic lupus erythematosus]. Zhongguo Zhong Xi Yi Jie He Za Zhi,1992,12:669-71,645.
[144] Ling Weng, Yan Liu, Xue-ying Liu,et al. Effect of Astragalus polysaccharide injectable powder (APS-P) on cytokine secretion of murine splenocytes and NK activity of S-180-bearing mice. Study J Trad Chin Med,2003,21:1522-1524.
[145] Ma ZH, Zhang CY, Liu X, et al. Research on antitumor effect of Astragalus mongholicus polysaccharide to 6 kinds of tumor strain in mice. Acta Chin Med Pharmacol, 1996,4:55-56.
[146] Yoshida Y, Wang MQ, Liu JN, et al. Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in particular. Int J Immunopharmacol,1997,19:359-70.
[147] Bao X, Liu C, Fang J, et al. Structural and immunological studies of a major polysaccharide from spores of Ganoderma lucidum (Fr.) Karst. Carbohydr Res,2001,332:67-74.
[148] Bao XF, Wang XS, Dong Q, et al. Structural features of immunologically active polysaccharides from Ganoderma lucidum. Phytochemistry,2002,59:175-81.
[149] Lin YL, Lee SS, Hou SM, et al. Polysaccharide purified from Ganoderma lucidum induces gene expression changes in human dendritic cells and promotes T helper 1 immune response in BALB/c mice. Mol Pharmacol,2006,70:637-44.
[150] Kim HM, Han SB, Oh GT, et al. Stimulation of humoral and cell mediated immunity by polysaccharide from mushroom Phellinus linteus. Int J Immunopharmacol, 1996,18:295-303.
[151] Yin G, Ardo L, Thompson KD, et al. Chinese herbs (Astragalus radix and Ganoderma lucidum) enhance immune response of carp, Cyprinus carpio, and protection against Aeromonas hydrophila. Fish Shellfish Immunol,2009,26:140-5.
[152] Wang SY, Hsu ML, Hsu HC, et al. The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer, 1997,70:699-705.
[153] Gao Y, Tang W, Dai X, et al. Effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer.J Med Food, 2005,8:159-68.
[154] Gao Y, Zhou S, Jiang W, et al. Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest, 2003,32:201-15.
[155] Peng X, Tian G. Structural characterization of the glycan part of glycoconjugate LbGp2 from Lycium barbarum L. Carbohydr Res, 2001,331:95-9.
[156] Ha KT, Yoon SJ, Choi DY, et al. Protective effect of Lycium chinense fruit on carbon tetrachloride-induced hepatotoxicity.J Ethnopharmacol,2005,96:529-35.
[157]Luo Q,Cai Y,Yan J,et al.Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts from Lycium barbarum.Life Sci,2004,76:137-49.
[158]Li XM,Ma YL,Liu XJ.Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice.J Ethnopharmacol,2007,111:504-11.
[159]Luo Q,Yan J,Zhang S.[Effects of pure and crude Lycium barbarum polysaccharides on immunopharmacology].Zhong Yao Cai,1999,22:246-9.
[160]Zhu J,Zhao LH,Chen Z.[Stimulation by Lycium bararum polysaccharides of the maturation of dendritic cells in murine bone marrow].Zhejiang Da Xue Xue Bao Yi Xue Ban,2006,35:648-52.
[161]Gan L,Zhang SH,Liu Q,et al.A polysaccharide-protein complex from Lycium barbarum upregulates cytokine expression in human peripheral blood mononuclear cells.Eur J Pharmacol,2003,471:217-22.
[162]Li ML,Liu ML.[Analysis of trace elements in fructus Ligustri Lucidi and its processed products].Zhongguo Zhong Yao Za Zhi,1989,14:727-9,762.
[163]Hao Z,Hang B,Wang Y.[Hypoglycemic effect of fructus Ligustri Lucidi].Zhongguo Zhong Yao Za Zhi,1992,17:429-31,447.
[164]Zhang Y,Lai WP,Leung PC,et al.Improvement of Ca balance by Fructus Ligustri Lucidi extract in aged female rats.Osteoporos Int,2008,19:235-42.
[165]Zhang Y,Dong XL,Leung PC,et al.Fructus ligustri lucidi extract improves calcium balance and modulates the calciotropic hormone level and vitamin D-dependent gene expression in aged ovariectomized rats.Menopause,2008,15:558-65.
[166]He J,Li Y,Wei S,et al.[Effects of mixture of Astragalus membranaceus,Fructus Ligustri lucidi and Eclipta prostrata on immune function in mice].Hua Xi Yi Ke Da Xue Xue Bao,1992,23:408-11.
[167]Ruan H,Lu Z.[Studies on immunomodulatory function of polysaccharide of Fructus Ligustri Lucidi].Zhongguo Zhong Yao Za Zhi,1999,24:691-3,704.
[168]李璘,邱蓉丽,周长慧,等.女贞子多糖对荷瘤小鼠免疫功能的影响.南京中医药大学学报,2008,6.388-390.
[169]Li ML.[Progress in the study on fructus Ligustri lucidi].Zhongguo Zhong Yao Za Zhi,1994,19:504-6.
[170]Liu T,Zheng X,Yang X,et al.[Quantity study of cultivated and wild Rhizoma Polygonati Odorati].Zhong Yao Cai,2005,28:14-6.
[171]Chen H,Feng R,Guo Y,et al.Hypoglycemic effects of aqueous extract of Rhizoma Polygonati Odorati in mice and rats.J Ethnopharmacol,2001,74:225-9.
[172]叶红翠,张小平,余红,等.多花黄精粗多糖抗肿瘤活性研究.中国实验方剂学杂志,2008,14:43-45.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |