茱萸丸矫正“免疫-炎症”网络失衡改善动脉粥样硬化的机制研究  

Study on Mechanism of Zhuyu Pills to Improve Atherosclerosis by Correcting"Immune-Inflammation"Imbalance

作　　者：宋玮 沈涛[1] SONG Wei;SHEN Tao(Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China)

机构地区：[1]成都中医药大学,四川成都610075

出　　处：《中药材》2024年第4期969-976,共8页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金项目(81973743);四川省科技厅重点研发项目(22ZYF0905)

摘　　要：目的:探讨茱萸丸对动脉粥样硬化斑块的影响及可能作用机制。方法:采用高脂饲料喂养ApoE^(-/-)小鼠诱导动脉粥样硬化模型。将造模成功的50只ApoE^(-/-)小鼠按照随机数字表法分为模型组、阿托伐他汀钙(10.40 mg/kg)组及茱萸丸低(130.54 mg/kg)、中(261.08 mg/kg)、高(522.16 mg/kg)剂量组,每组10只。以10只C57BL/6J小鼠作为正常对照组,给予普通饮食饲养。各给药组灌胃给予相应药物,正常对照组及模型组给予相应体积生理盐水灌胃,1次/d,连续灌胃12 w。采用生化法检测肝组织TC、TG、LDL-C、HDL-C水平;全自动生化仪检测空腹血糖水平;HE染色观察小鼠主动脉、肝脏、脂肪组织病理学变化;ELISA检测血清胰岛素、TNF-α、IL-6、IL-4、IL-10水平;免疫荧光法检测肝组织CD1d蛋白表达;流式细胞术检测肝脏iNKT细胞变化;实时荧光PCR法检测小鼠肝组织CD1d mRNA表达及主动脉组织TNF-α、IL-6、IL-4、IL-10 mRNA表达。结果:与正常对照组比较,模型组小鼠肝组织TC、TG、LDL-C水平显著升高,HDL-C水平显著降低,胰岛素抵抗指数显著升高(P<0.01),主动脉斑块面积明显增大,肝脏出现脂肪样变及大量脂滴,脂肪细胞体积膨大,血清TNF-α、IL-6水平显著升高,IL-4、IL-10水平显著降低,肝组织CD1d mRNA及蛋白表达显著升高,iNKT数量显著增多,主动脉组织TNF-α、IL-6 mRNA表达显著升高,IL-4、IL-10 mRNA表达显著降低(P<0.01)。与模型组比较,各给药组小鼠肝组织TC、TG、LDL-C水平显著降低,HDL-C水平显著升高,胰岛素抵抗指数显著降低(P<0.05或P<0.01),主动脉斑块面积明显缩小,肝脏脂质沉积明显减轻,脂滴明显减少,脂肪细胞体积明显缩小,血清TNF-α、IL-6水平显著降低,IL-4、IL-10水平显著升高,肝组织CD1d mRNA及蛋白表达显著降低,iNKT数量显著减少,主动脉组织TNF-α、IL-6 mRNA表达显著降低,IL-4、IL-10 mRNA表达显著升高(P<0.01)。结论:茱萸丸对小鼠动脉粥样硬�Objective:To investigate the effect of Zhuyu pills on atherosclerotic plaque and its possible mechanism.Methods:The ApoE^(-/-)mice atherosclerosis model was establish by fed high fat diet.Fifty ApoE^(-/-)mice were divided into model group,atorvastatin calcium(10.40 mg/kg)group and Zhuyu pills low(130.54 mg/kg),medium(261.08 mg/kg)and high(522.16 mg/kg)dose groups with 10 mice in each group according to random number table method.Ten C57BL/6J mice were taken as normal control group and fed with ordinary diet.Each administration group was given the corresponding drugs by intragastric administration,and the mice in normal control group and model group were given the corresponding volume of normal saline by intragastric administration,once a day,continuous intragastric administration for 12 weeks.The levels of TC,TG,LDL-C and HDL-C in liver tissue were detected by biochemical method.The fasting blood glucose level was detected by automatic biochemical analyzer.The histopathological changes of aorta,liver and adipose tissue were observed by HE staining.Serum levels of insulin,TNF-α,IL-6,IL-4 and IL-10 were detected by ELISA.The expression of CD1d protein in liver tissue was detected by immunofluorescence.The changes of iNKT cells in liver were detected by flow cytometry.The expressions of CD1d mRNA in liver and TNF-α,IL-6,IL-4 and IL-10 mRNA in aorta tissue were detected by real-time PCR.Results:Compared with the normal control group,the levels of TC,TG and LDL-C in liver tissue of model group were significantly increased,HDL-C level was significantly decreased,insulin resistance index was significantly increased(P<0.01),aortic plaque area was obviously increased,lipopathia and large amount of fat droplets appeared in liver,fat cell volume expanded,and serum levels of TNF-αand IL-6 were significantly increased.The levels of IL-4 and IL-10 were significantly decreased,the expressions of CD1d mRNA and protein in liver tissue were significantly increased,the number of iNKT was significantly increased,the mRNA expressi

关 键 词：动脉粥样硬化 茱萸丸 CD1d-iNKT细胞轴 苦辛化浊 

分 类 号：R285.5[医药卫生—中药学]