益气活血方对冠心病气虚血瘀证大鼠TLR4/MyD88/NF-κB信号通路的影响  

Effect of Yiqi Huoxu e Formula on TLR4/MyD88/NF-κB Signal Pathway in Rats with Coronary Heart Disease Qi Deficiency and Blood Stasis Syndrome

作　　者：陈善达 汪顺伟 欧颖 荆晓朔 李静[1,2,3] 吴华英 李亮 CHEN Shanda;WANG Shunwei;OU Ying;JING Xiaoshuo;LI Jing;WU Huaying;LI Liang(Hunan University of Chinese Medicine,Changsha 410208,China;Provincial Key Laboratory of TCM Diagnostics,Changsha 410208,China;Key Laboratory of TCM Heart and Lung Syndrome Differentiation and Medical Diet and Dietotherapy,Changsha 410208,China;College of Medicine,Hunan Normal University,Changsha 410013,China)

机构地区：[1]湖南中医药大学,长沙410208 [2]中医诊断学湖南省重点实验室,长沙410208 [3]中医心肺病证辨证与药膳食疗重点研究室,长沙410208 [4]湖南师范大学医学院,长沙410013

出　　处：《中国中医基础医学杂志》2024年第2期226-231,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：湖南省自然科学基金面上项目(2019JJ40214);湖南省中医药科研计划一般项目(2021121);湖南省中医药科研计划项目(202004);湖南省教育厅优秀青年项目(21B0081);湖南省中医药管理局一般项目(D2022027)。

摘　　要：目的探讨益气活血方对冠心病气虚血瘀证大鼠的影响。方法48只雄性SD大鼠随机分为假手术组、模型组、益气活血方组、单硝酸异山梨酯组。除假手术组外,所有大鼠行冠状动脉结扎术。术后7 d,除假手术组外,其余大鼠强迫游泳14 d,并控制大鼠的食量,同时益气活血方组和单硝酸异山梨酯组大鼠予灌胃给药28 d。心脏超声检测大鼠心功能;全血黏度检测大鼠的瘀血程度;苏木精-伊红(hematoxylin-eosin,HE)染色检测大鼠心脏病理形态改变;Masson染色检测大鼠心肌纤维化水平;荧光定量PCR和免疫组化检测大鼠心肌组织Toll样受体(toll-like receptor,TLR)4、髓样分化因子(myeloid differentiationfactor,MyD)88和核因子(nuclear-factor,NF)-κB p65的mRNA和蛋白表达量;ELISA检测大鼠血清中白细胞介素(interleukin,IL)-1β、IL-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α的含量。结果与假手术组比较,模型组大鼠心功能下降(P<0.01),全血黏度升高(P<0.01),心肌组织排列紊乱,心肌损伤范围较大,心肌纤维化严重(P<0.01),心肌中TLR4、MyD88、NF-κB p65 mRNA及蛋白表达水平上调(P<0.01),血清中IL-1β、IL-6、TNF-α的含量升高(P<0.01);与模型组比较,药物干预后,大鼠心功能改善(P<0.05),全血黏度下降(P<0.01),心肌组织排列较整齐,心肌损伤范围缩小,心肌纤维化缓解(P<0.01),TLR4、MyD88、NF-κB p65 mRNA及蛋白表达水平下调(P<0.05),血清中IL-1β、IL-6、TNF-α含量减少(P<0.05)。结论益气活血方能通过抑制TLR4/MyD88/NF-κB p65信号通路介导的炎症反应发挥对冠心病气虚血瘀证大鼠的治疗作用。Objective To investigate the effect of Yiqi Huoxue Formula(YQHXF)on rats with coronary heart disease with Qi deficiency and blood stasis syndrome.Methods 48 male SD rats were randomly divided into sham group,model group,YQHXF group and isosorbide mononitrate group.Rats in the latter 3 groups underwent surgery of coronary artery ligation.After 7 days,except for the sham operation group,the rats in the other groups were forced to swim for 14 days and their food intake was limited.At the same time,rats of YQHXF group and isosorbide mononitrate group were intervened with corresponding medicine for 28 days.Cardiac function of rats was detected by cardiac ultrasound.Blood stasis degree of rats was detected by whole blood viscosity.HE staining was used to detect the pathological changes of the heart tissue.Masson staining was used to detect the degree of myocardial fibrosis of rats.The mRNA and protein expression of toll-like receptor(TLR)4,myeloid differentiationfactor(MyD)88 and nuclear-factor(NF-κB)p65 in myocardium were detected by quantitative real-time PCR and immunohistochemistry.The content of interleukin(IL)-1β,IL-6 and TNF-αin serum of rats was detected by ELISA.Results Compared with sham group,rats in model group had decreased cardiac function(P<0.01),increased whole blood viscosity(P<0.01),disordered myocardial tissue arrangement,larger range of myocardial damage,and severe myocardial fibrosis(P<0.01),TLR4,MyD88,and NF-κB p65 mRNA and protein expression levels were increased in the myocardium(P<0.01),and the levels of IL-1β,IL-6,and TNF-αin the serum were increased(P<0.01).Compared with model group,after drug intervention,cardiac function of the rats was improved(P<0.05),whole blood viscosity was decreased(P<0.01),myocardial tissue was neat,damaged area of myocardial tissue was narrowed,myocardial fibrosis was relieved(P<0.01),the mRNA and protein expression level of TLR4,MyD88 and NF-κB p65 were lowered(P<0.05),the level of IL-1β,IL-6,TNF-αwas decreased(P<0.05).Conclusion YQHXF can inhibit inflamma

关 键 词：冠心病 气虚血瘀证 益气活血方 TLR4/MyD88/NF-κB信号通路 炎症 

分 类 号：R259[医药卫生—中西医结合] R2-03[医药卫生—中医内科学]