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,cTnI and 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 group,GXN high-dose group could significant improvements in myocardial tissue injury,cardiac function index,lipid index,oxidative index,inflammatory factors and mRNA and protein expression of TLR4,PI3K,AKT and mTOR in myocardial tissue of CHD rats(P＜0.05).CONCLUSION GXN can improve myocardial injury and blood lipids level of CHD rats,and inhibit inflammation and oxidative stress response,which is related to the activation of TLR4/PI3K/AKT/mTOR pathway.
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