玛诺系汤冠心宁浸膏对冠心病大鼠心肌损伤的保护作用及机制研究  

Protective Effects and Mechanisms of Manuo Xitang GuanXinNing Extractum Against Myocardial Injury in Rats with Coronary Heart Disease

作　　者：多杰 佳哇 东知多杰 赛桑杰 李啟恩 Duojie;Jiawa;Dongzhiduojie;Saisangjie;LI Qien(Qinghai Institute of Tibetan Medicine,Xining 810016,China;State Key Laboratory of Tibetan Medicine Research and Development,Xining 810016,China)

机构地区：[1]青海省藏医药研究院,西宁810016 [2]藏药新药开发国家重点实验室,西宁810016

出　　处：《中国现代应用药学》2024年第21期2998-3009,共12页Chinese Journal of Modern Applied Pharmacy

基　　金：青海省科技成果转化专项项目(2020-SF-130)。

摘　　要：目的探究玛诺系汤冠心宁浸膏(Manuo Xitang GuanXinNing extractum,GXN)对冠心病(coronary heart disease,CHD)大鼠心肌损伤的保护作用及机制。方法采用高脂饲料饲喂和垂体后叶素注射建立大鼠CHD模型,并实施GXN干预。利用超高分辨率小动物超声影像系统,监测大鼠的心率(heart rate,HR)、左心室舒张期内径(left ventricular diastolic diameter,LVIDd)、左心室收缩期内径(left ventricular systolic diameter,LVIDs)、短轴缩短率(fractional shortening,FS)和射血分数(ejection fraction,EF);利用全自动生化分析仪检测血清总胆固醇(total cholesterol,TC)、甘油三酯(triacylglycerol,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(highdensity lipoprotein cholesterol,HDL-C)、乳酸脱氢酶(lactate dehydrogenase,LDH)、肌酸激酶同工酶-MB(creatine kinase isoenzyme-MB,CK-MB)和C反应蛋白(C-reactive protein,CRP)的水平;用ELISA试剂盒测定血清肌酸激酶(creatine kinase,CK)、心肌肌钙蛋白I(cardiac troponinⅠ,cTnI)、丙二醛(malonaldehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的水平;HE染色观察心肌组织的病理学变化;免疫组化技术检测心肌组织中IL-6、IL-1β和TNF-α的表达;分别测定心肌组织中TLR4、PI3K、AKT、mTOR mRNA及蛋白的相对表达。结果与正常组相比,模型组大鼠心肌组织可见细胞变性、坏死,大量炎性细胞浸润;心功能指标LVIDs、LVIDd,血脂指标TC、TG和LDL-C,心肌损伤指标LDH、CK、CK-MB、cTnΙ和CRP,以及氧化指标MDA均发生极显著升高(P<0.01);促炎因子IL-6、IL-1β和TNF-α在心肌组织中呈阳性表达;而心功能指标HR、EF和FS,氧化指标SOD、GSH-Px,血脂指标HDL-C,心肌组织中TLR4、PI3K、AKT、mTOR的mRNA及蛋白表达均显著降低(P<0.05)。与模型组相比,GXN高剂量组大鼠的心肌组织损伤、心功能指标、血脂指标、氧化指标、OBJECTIVE To investigate the protective effects and mechanisms of Manuo Xitang GuanXinNing extractum(GXN)against myocardial injury in rats with coronary heart disease(CHD).METHODS CHD rat model was established by high-fat diet feeding and pituitrin injection,then followed by GXN intervention.Heart rate(HR),left ventricular systolic diameter(LVIDs),left ventricular diastolic diameter(LVIDd),ejection fraction(EF)and fractional shortening(FS)of rats were measured by ultra-high resolution small animal ultrasound imaging system.Serum levels of total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),lactate dehydrogenase(LDH),creatine kinase isoenzyme-MB(CK-MB)and C-reactive protein(CRP)were determined by automatic biochemical analyzer.Serum creatine kinase(CK),cardiac troponin I(cTnI),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)levels were determined by ELISA kits.Pathological changes of myocardial tissue of rats were observed with HE staining,and protein expressions of IL-6,IL-1β and TNF-α were detected by immunohistochemistry.Relative expressions of TLR4,PI3K,AKT and mTOR mRNA and proteins were detected respectively.RESULTS Compared with the normal group,myocardial tissue of rats in model group showed cell degeneration,necrosis and a large number of inflammatory cells infiltration.Compared with normal rats,there were significantly increased of cardiac function indicators included LVIDs and LVIDd,lipid indicators included TC,TG and LDL-C,myocardial injury indicators included LDH,CK,CK-MB,cTnΙand CRP,and oxidative indicators MDA(P<0.01).Meanwhile,the pro-inflammatory factors IL-6,IL-1β and TNF-α positively expressed in myocardial tissue.The cardiac function indexes included HR,EF and FS,oxidative indexes included SOD,GSH-Px,lipid indexes included HDL-C,as well as mRNA levels and protein expression of TLR4,PI3K,AKT and mTOR in myocardial tissue were all significantly reduced(P<0.05).Compared with model grou

关 键 词：玛诺系汤冠心宁 冠心病 炎症 氧化应激 

分 类 号：R285.5[医药卫生—中药学]