氧化苦参碱通过调节氧化应激和炎症减轻糖尿病大鼠心肌病变OA

Objective To explore the effects of oxymatrine(OMT)on oxidative stress and inflammatory response in myocardial lesions of diabetes mellitus(DM)rats.Methods The DM rat models were established by high-sugar and high-fat diet combined with one-time intraperitoneal injection of STZ(45 mg/kg).The DM rats were divided into DM group,25 mg OMT group,100 mg OMT group and Nrf2 inhibitor group(OMT+inhibitor group),and the unmodeled rats were chosen as control group,with 10 rats in each group.The treatment continued for 4 weeks.At 12 h after the last administration,left ventricular shortening fraction(LVFS),left ven-tricular ejection fraction(LVEF),fasting plasma glucose(FPG),fasting insulin(FINS)levels and myocardial mass of rats in each group were detected respectively,and the insulin resistance index(HOMTA-IR)and the ratio of myocardial mass to body weight were calculated.The inflammatory lesions and fibrosis of myocardial tissue were observed by HE staining and Masson staining,and the apoptosis level of myocardial cells was detected by TUNEL staining.The levels of ATP,SOD,GSH-Px and MDA in myocardial tissue were detected by reagent kits,and the level of ROS was detected by DHE probes.The protein expressions of TNF-α,IL-6,IL-1β,Nrf2,HO-1 and NQO1 in myocardial tissue were detected by Western blot.Results The morphology and structure of myocardial tissue in control group were intact,the inflammatory lesions and fibrosis of myocardial tissue in DM group were severe,the myocardial tissue lesions in 25 mg OMT group and 100 mg OMT group were reduced,and the injury of myocardial tissue in OMT+inhibitor group was similar to that in DM group.Compared with control group,the ratio of heart mass to body mass,FPG,FINS and HOMTA-IR levels increased in DM group(P<0.05),while LVEF and LVFS decreased(P<0.05);the level of myocardial cell apoptosis,the protein expressions of IL-1β,IL-6 and TNF-α,and levels of MDA and ROS in myocardial tissue increased(P<0.05),while the levels of ATP,SOD and GSH-Px,and the protein expressions of Nrf2,HO-1 and NQO1 decreased(P<0.05).Compared with DM group,the ratio of heart mass to body mass,FPG,FINS and HOMTA-IR levels decreased in 25 mg OMT and 100 mg OMT group(P<0.05),while LVEF and LVFS values increased(P<0.05);the level of myocardial cell apoptosis,the protein expressions of IL-1β,IL-6 and TNF-α,and levels of MDA and ROS in myocardial tissue decreased(P<0.05),while the levels of ATP,SOD and GSH-Px,and the protein expressions of Nrf2,HO-1 and NQO1 increased(P<0.05).All indicators showed better improvement in 100 mg OMT group than in 25 mg OMT group.Compared with 100 mg OMT group,the ratio of heart mass to body mass,FPG,FINS levels and HOMTA-IR increased in OMT+inhibitor group(P<0.05),while LVEF and LVFS decreased(P<0.05);the level of myocardial cell apoptosis,the protein expressions of IL-1β,IL-6 and TNF-α,and levels of MDA and ROS in myocardial tissue increased(P<0.05),while the levels of ATP,SOD and GSH-Px,and the protein expressions of Nrf2,HO-1 and NQO1 decreased(P<0.05).Conclusion Oxymatrine can improve myocardial lesions in diabetic rats by the inhibition of oxidative stress and inflammatory response.