黄连解毒汤对高脂饮食apoE^(-/-)小鼠全身和主动脉血管局部免疫反应影响的研究  

Protection of Huanglian Jiedu Decoction on Systemic and Vascular Immune Responses of High Fat Induced apoE^(- /-) Mice

作　　者：马雅銮[1] 王蓓蓓[2] 韩俊燕[2] 李蕊[2] 张卫梅[2] 李彤[2] 陈冰[1] 苏静[1] 王宪波[2] 曾辉[2] 

机构地区：[1]中国中医科学院中医基础理论研究所分子生物学实验室,北京100700 [2]首都医科大学附属北京地坛医院传染病研究所,北京100011

出　　处：《中国中西医结合杂志》2013年第11期1520-1525,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.81072938);北京市自然科学基金资助项目(No.7102119);中华人民共和国人力资源和社会保障部留学人员科技活动择优资助优秀类项目(No.2010)

摘　　要：目的观察黄连解毒汤对高脂饮食喂养的apoE基因敲除(apoE-/-)小鼠全身和主动脉血管局部免疫反应的影响。方法以8只野生型C57BL6小鼠为野生普食组,24只apoE-/-小鼠随机分为apoE-/-普食组、apoE-/-高脂组、apoE-/-高脂加中药组,每组8只。普食组与高脂组分别给予普食和高脂饮食4周。ApoE-/-高脂加中药组同时给予黄连解毒汤5 g/(kg·d)灌胃,其他小鼠采用等量纯净水灌胃。4周后,检测血脂水平、外周血单核细胞比例及其表面Toll样受体4(Toll-like receptor 4,TLR4)和清道夫受体CD36的表达;检测主动脉病理变化和主动脉血管局部细胞因子表达水平;进一步采用脂多糖(Lipopolysaccharide,LPS)刺激检测血浆细胞因子的水平。结果 (1)与野生普食组比较,apoE-/-普食组TC、TG和LDL-C水平显著升高(P<0.05,P<0.01);与apoE-/-普食组比较,apoE-/-高脂组TC和LDL-C水平显著增高(P<0.05);apoE-/-高脂组与apoE-/-高脂加中药组血脂各项指标比较,差异无统计学意义(P>0.05)。(2)与野生普食组比较,apoE-/-普食组外周血单核细胞比例无明显变化,TLR4表达水平显著增多(P<0.05);与apoE-/-普食组比较,apoE-/-高脂组小鼠外周血单核细胞比例及TLR4表达水平显著增多(P<0.05);与apoE-/-高脂组比较,apoE-/-高脂加中药组外周血单核细胞比例及其表面TLR4表达显著降低,清道夫受体CD36表达水平亦显著降低(P<0.05)。(3)LPS刺激3 h后,与野生普食组比较,apoE-/-普食组血浆TNF-α和IL-10表达显著增加(P<0.05);与apoE-/-普食组比较,apoE-/-高脂组小鼠血浆IL-12、TNF-α、MCP-1和IL-10表达增加,但差异无统计学意义(P>0.05);黄连解毒汤干预4周后,与apoE-/-高脂组比较,apoE-/-高脂加中药组MCP-1表达显著下调,而IL-10水平进一步显著上升,差异有统计学意义(P<0.05)。(4)与野生普食组比较,apoE-/-普食组主动脉血管壁炎症因子IFN-γ、MCP-1、TNF-α和IL-1βmRNA水平显著升高,抑炎因子IL-10亦显著升高(P<0Objective To observe the effect of Huanglian Jiedu Decoction （HJD） on systemic and vascular immune responses of high fat diet fed apoE deficient （apoE-/-） mice. Methods Eight wild type C57BL6 mice were recruited as the wild type common food group. Totally 24 apoE-/- mice were ran- domly divided into the ApoE-/-common food group, the ApoE-/- hyperlipidemia group, and the ApoE-/- hyperlipidemia plus HJD group, 8 in each group. In the present study, the common food mice and high fat fed mice were fed with a chow diet or a high cholesterol diet for 4 weeks. HJD was given to mice in the ApoE-/- hyperlipidemia plus HJD group at the daily dose of 5 g/kg by gastrogavage, while equal volume of pure water was given to mice in the rest groups by gastrogavage. Four weeks later, the plasma levels of blood lipids, the ratio of peripheral blood mononuclear cells, and expressions of Toll-like receptor 4 （TLR-4） and CD36 on the monocytes were detected. The pathological changes and expressions of cyto- kines in local aorta were detected. The plasma cytokine levels in response to lipopolysaccharide （LPS） were analyzed. Results （1） Compared with the wild type common food group, TC, TG, and LDL-C sig- nificantly increased in the ApoE-/-common food group （P 〈0.05,P 〈0.01 ）. Compared with the ApoE-/- common food group, TC and LDL-C significantly increased in the hyperlipidemia group （P 〈0.05）. There was no statistical difference in each index between the ApoE-/- hyperlipidemia group and the ApoE-/- hy- perlipidemia plus HJD group （P〉0.05）. （2） Compared with the wild type common food group, no obvi- ous change of the ratio of peripheral blood mononuclear cells happened, the TLR4 expression level signif- icantly increased in the ApoE-/-common food group （P 〈0.05）. Compared with the ApoE-/-common food group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly in- creased in the ApoE-/- hyperlipidemia group （P 〈 0.05）. Compared with the ApoE-/-

关 键 词：黄连解毒汤 APO E基因敲除小鼠 高脂血症 单核细胞 细胞因子 

分 类 号：R285.5[医药卫生—中药学]