摘要
目的:通过Toll样受体(TLR)信号通路探讨心脑络泰胶囊对心肌梗死(myocardial infarction,MI)的作用机制。方法:100只雄性SD大鼠随机分为假手术对照组、模型对照组、脑心通110 mg/kg组、心脑络泰胶囊16.2、32.4、64.8 mg/kg组。采用结扎左冠状动脉前降支根部的方式构建疾病模型。以舌象、力竭游泳时间、抓力评价模型所属证候;采用氯化三苯四氮唑(TTC)法测定心肌梗死率;检测心电图、心肌酶、血清炎性因子观察药效;HE染色观察心肌组织病理状况;利用qRT-PCR和Western blotting法检测TLR相关基因和蛋白的相对表达。结果:与假手术对照组比较,模型对照组大鼠心脏出现明显的ST段抬高和大面积梗死区域,说明造模成功,舌象、力竭游泳时间、抓力实验证明造模大鼠为气虚血瘀所诱发的MI,模型对照组大鼠心肌酶谱指标和炎性因子含量显著升高(P<0.01),可见心肌细胞片状梗死、溶解,并伴有大量炎性细胞浸润,心肌组织中α干扰素(IFN-α)、干扰素调节因子7(IRF7)、髓样分化因子88(MyD88)、转录因子κB(NF-κB)、Toll样受体2(TLR2)、TLR4、TLR7、TLR9、肿瘤坏死因子-α(TNF-α)的蛋白及mRNA表达明显上调(P<0.05或P<0.01);与模型对照组相比,脑心通110 mg/kg组、心脑络泰胶囊32.4、64.8 mg/kg组大鼠力竭游泳时间、抓力显著升高,心肌梗死率明显降低,心肌酶谱指标和炎性因子明显降低(P<0.05或P<0.01),病理损伤有所恢复,心肌组织中IFN-α、IRF7、MyD88、NF-κB、TLR2、TLR4、TLR7、TLR9、TNF-α蛋白及mRNA表达下调(P<0.05或P<0.01)。结论:心脑络泰胶囊可通过调节TLR相关信号通路抑制心脏炎症、减轻心肌梗死气虚血瘀证和改善心肌组织。
Objective:To explore the mechanism of Xinnao Luotai(心脑络泰)Capsules on myocardial infarction(MI)via the Toll-like receptor(TLR)signaling pathway.Methods:One hundred male SD rats were randomly divided into a sham operation control group,a model control group,a Naoxintong(脑心通)(110 mg/kg)group,and Xinnao Luotai Capsules groups(64.8,32.4,16.2 mg/kg).An MI model was established by ligating the left anterior descending coronary artery.Syndromes of the model were manifested by tongue characteristics,exhaustive swimming time,and grip strength.MI rate was measured using triphenyl tetrazolium chloride(TTC)staining.The pharmacodynamic efficacy of these medicines was observed by electrocardiogram,myocardial enzymes,and serum inflammatory factors.Pathological changes of myocardium tissue were observed by hematoxylin and eosin(HE)staining,while Tlr-related mRNA and protein expression levels were detected by qRT-PCR and Western blot.Results:Compared with the sham operation control group,the model group exhibited significant ST segment elevation and massive infarct areas,confirming successful modeling.Tongue characteristics,exhaustive swimming time,and grip strength suggested that the MI model was induced by Qixu Xueyu(气虚血瘀)syndrome.Myocardial enzyme levels and inflammatory factors were significantly elevated in model rats(P<0.01).Pathological analysis revealed local speckled infarction and dissolution in myocardial cells,with a large number of inflammatory cell infiltrations.The protein and mRNA expressions of interferon-α(IFN-α),interferon regulatory factor 7(IRF7),myeloid differentiation factor 88(MyD88),nuclear factorκB(NF-κB),Toll-like receptors(TLR2,TLR4,TLR7,and TLR9),and tumor necrosis factor-α(TNF-α)were significantly increased in myocardial tissue(P<0.05 or P<0.01).Compared with the model control group,all Xinnao Luotai groups showed reduced myocardial enzymes and inflammatory factors,while the pathological damage was recovered.The protein and mRNA expressions of IFN-α,IRF7,MyD88,NF-κB,TLR2,TLR4,TLR7,TLR9,and TNF-αwere decreased in myocardial tissue,while the most significant interventive effect occurred in the 64.8 mg/kg Xinnao Luotai group(P<0.05 or P<0.01).Conclusion:By regulating the TLR related signaling pathway,Xinnao Luotai Capsules can inhibit cardiac inflammation and alleviate MI with Qixu Xueyu syndrome,improving myocardial tissue.
作者
张振东
王鹏
刘秋月
王克婧
刘树民
闫久江
孟杰
卢芳
陈平平
ZHANG Zhendong;WANG Peng;LIU Qiuyue;WANG Kejing;LIU Shumin;YAN Jiujiang;MENG Jie;LU Fang;CHEN Pingping(Graduate School of Heilongjiang University of Chinese Medicine,Harbin 150040;Institute of Traditional Chinese Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040;Heilongjiang Zhenbaodao Pharmaceutical Co.,Ltd,Harbin 150030)
出处
《中药药理与临床》
北大核心
2025年第10期11-16,共6页
Pharmacology and Clinics of Chinese Materia Medica
基金
黑龙江省科技厅药企合作课题(编号:2023-Z004)。
关键词
心脑络泰胶囊
心肌梗死
TOLL样受体
免疫和炎症反应
Xinnao Luotai Capsules
Myocardial infarction
Toll-like receptor
Immune and inflammatory response
