Effect Of Total Alkaloids Of Rhizoma Coptidis And Panax Notoginseng Saponins On Diabetic Patients With Coronary Heart Disease And Its Mechanism

Objective:To clarify the compatibility ratio of rhizoma coptidis total alkaloids and panax notoginseng total saponins in the treatment of diabetic coronary heart disease and the therapeutic effect on diabetic coronary heart disease.Methods:（1）The total alkaloid of Rhizoma Coptidis and Panax Notoginseng Saponins were used as the research object.U6（6²）table was choosed for grouping design.The content of triglyceride FBG（fasting blood-glucose）,PT（prothrombin time,PT）and APTT（active partial thromboplastin time,APTT）was chosen as index.The best dose ratio was obtained by multiple regression analysis.（2）Mice model of diabetic myocardial injury was established by high-fat diet combined with streptozotocin injection to study the two drug regimens of prevention and treatment.Mice were randomly divided into blank group,model group,metformin group,xuesaitong group and HS composition group.Blood glucose,glucose tolerance,lipid,CK,IL-6 and TNF-αlevels were observed.Apoptosis of myocardial cells was detected by TUNEL staining,pathological changes of pancreas and myocardial tissues were observed by HE staining,and protein expressions of NF-B,Bax,bcl-2 and caspase-3 were detected by immunohistochemical staining.The treated mice were randomly divided into blank group,model group,metformin group,xuesetong group and HS composition group.Blood glucose,glucose tolerance,lipid,IL-6 and TNF-αlevels were observed.Pathological changes of pancreas and myocardium were observed by HE staining.（3）Wistar rats were selected and streptozotocin injection combined with coronary artery ligation was used to prepare the model of diabetic myocardial ischemia-reperfusion injury.The rats were randomly divided into blank group,model group,metformin group and HS composition group,and serum insulin,blood glucose,glucose tolerance,SOD and MDA levels were detected.HE staining was used to observe the pathological changes of rat pancreas and myocardial tissue,and Western Blot was used to detect the expression level of rat myocardial tissue protein.Results:（1）The optimal compatibility ratio of HS composition was 625mg·kg^-1+60mg·kg^-1 of total alkaloids of rhizoma coptidis and total saponins of panax notoginseng.（2）The preventive administration of HS composition group could significantly reduce the blood glucose of diabetic mice.After administration,serum lipids,CK,IL-6 and TNF-αlevels of mice were significantly decreased.The expressions of NF-κB,Bax and caspase-3 in myocardial tissue were decreased（P<0.01,P<0.05,P<0.05）and the expressions of Bcl-2 were increased（P<0.05）.The apoptosis index of cardiomyocytes in HS composition group was decreased（P<0.05）.The administration of HS composition could significantly reduce the blood glucose of diabetic mice.After administration,serum lipid,IL-6 and TNF-αlevels in mice were significantly decreased,and the pancreatic and myocardial tissue damage in mice was less severe than that in the model group.（3）The HS composition can reduce the Fast blood glucose,increase the insulin level（P<0.001）,improve the oral glucose tolerance and oxidative stress,reduce the expression of NOX2（P<0.01）,NOX4（P<0.05）,NLRP3（P<0.05）,Bax（P<0.01）and caspase-3（P<0.05）,and increase the expression of bcl-2（P<0.05）.To alleviate the damage of pancreatic and myocardial tissues in rats.Conclusion:The total alkaloid of Rhizoma Coptidis and Panax Notoginseng Saponins composition can inhibit the expression of NOX2,NOX4 and NLRP3,inhibit the oxidative stress and inflammatory response of myocardium,improve the apoptosis of cardiomyocytes,and reduce the myocardial injury caused by diabetes mellitus and coronary heart disease by lowering blood glucose and raising insulin levels.