黄芪-黄连药对通过激活STAT5信号通路诱导Th17/Treg平衡抑制小鼠动脉粥样硬化  

Huangqi-Huanglian herb pair attenuates atherosclerosis in mice by regulating Th17/Treg balance and activating STAT5 signaling pathway

作　　者：吴斯佳 李兆钰 马度芳 王琳[1] 张永健 王永成 王文婷 李晓[2] WU Si-jia;LI Zhao-yu;MA Du-fang;WANG Lin;ZHANG Yong-jian;WANG Yong-cheng;WANG Wen-ting;LI Xiao(Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China)

机构地区：[1]山东中医药大学,济南250014 [2]山东中医药大学附属医院,济南250014

出　　处：《中华中医药杂志》2023年第6期2544-2549,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：山东省重点研发计划(No.2019GSF108024);国家自然科学基金项目(No.82074388);山东省卫健委中西医结合防治常见病、多发病项目(No.YXH2019);山东省自然科学基金青年项目(No.ZR2020QH307);中国博士后科学基金第70批面上资助(No.2021M702043)。

摘　　要：目的:观察黄芪-黄连药对对Th17/Treg平衡及STAT5信号通路的影响,探讨其抑制动脉粥样硬化的机制。方法:30只ApoE^(-/-)小鼠随机分为模型组、芪-连组、芪-连+抑制剂组,每组10只,高脂饮食饲养12周诱导动脉粥样硬化模型;另取10只C57BL/6小鼠作为空白组。于高脂饮食干预的第13周开始给予相应药物灌胃治疗,共6周。检测血清甘油三酯(TG)、总胆固醇(TC)、基质金属蛋白酶-9(MMP-9)、白介素(IL)-10、IL-17表达水平,油红O染色观察主动脉壁脂质沉积情况;Western blot检测主动脉组织IL-17、叉头/翼状螺旋转录因子3(Foxp3)、p-STAT5、STAT5蛋白表达;流式细胞术检测脾脏辅助性T细胞(Th)17、调节性T细胞(Treg)细胞比率。结果:与模型组比较,芪-连组小鼠血脂、动脉壁脂质沉积面积占比、血清MMP-9及炎症因子水平、IL-17蛋白表达显著降低(P<0.01),Th17/Treg失衡得以改善(P<0.01);Foxp3、p-STAT5/STAT5蛋白表达显著升高(P<0.01);与芪-连组比较,芪-连+抑制剂组粥样硬化的改善作用及免疫调节功能显著减弱(P<0.05,P<0.01)。结论:黄芪-黄连药对可抑制动脉粥样硬化进展,其机制与激活STAT5信号通路、调节Th17/Treg淋巴细胞平衡从而抑制炎症反应有关。Objective:To observe the effect of Huangqi-Huanglian herb pair on the balance of Th17/Treg cells and STAT5 signal pathway,and to explore the mechanism of Huangqi-Huanglian herb pair on inhibiting atherosclerosis.Methods:Thirty ApoE^(-/-)mice were fed with high-fat-diet for 12 weeks to establish AS model,all those mice were divided into 3 groups:model group,Huangqi-Huanglian group,Huangqi-Huanglian+STAT5 inhibitor group,10 mice per group,and 10 C57BL/6 mice at 8weeks of age were fed as control group.And the corresponding drugs were given by intragastric administration for 6 weeks after 13 weeks of dietary intervention.The blood centrifuged was collected for detecting serum levels of triglyceride(TG),total cholesterol(TC),matrix metalloproteinase(MMP)-9,interleukin(IL)-10,IL-17with ELISA.The aortic tissue of mice was collected to detect lipid deposition by oil-red-O.Western blot was used to assay IL-17,fork/wing helix transcription factor 3(Foxp3),p-STAT5 and STAT5 expression.Flow cytometry was used to detect the Th17,Treg cells in spleen tissue of mice.Results:Compared with the model group,the levels of serum TC,TG and lipid deposition area of aorta,serum MMP-9,inflammatory factors and the level of IL-17 protein were significantly reduced in Huangqi-Huanglian group(P<0.01),and the imbalance of Th17/Treg was improved(P<0.01),and the level of Foxp3 and p-STAT5/STAT5 protein was increased(P<0.01).Compared with Huangqi-Huanglian group,the improvement of atherosclerosis and immunomodulatory function of Huangqi-Huanglian+STAT5 inhibitor group was significantly weakened(P<0.05,P<0.01).Conclusion:These results indicate that Huangqi-Huanglian herb pair can inhibit the progression of atherosclerosis,through activating STAT5 signaling pathway and regulating the balance of Th17/Treg lymphocytes to inhibit inflammatory reaction.

关 键 词：动脉粥样硬化 Th17/Treg平衡 黄芪-黄连药对 ApoE^(-/-)小鼠 STAT5信号通路 

分 类 号：R285.5[医药卫生—中药学]