The Protective Effect Of Endogenous ACE2 Agonists On Diabetic Cardiomyopathy And Its Possible Mechanism

Objective : 1.Diminazene aceturate(DIZE)as a new novel ACE2 endogenous agonists.To observe whether DIZE can endogenously stimulate ACE2.2.To observe the protective effect of DIZE on myocardium of diabetic cardiomyopathy rats and to explore its possible mechanism.Method: 1.Animal model establishment: 46 healthy male Wistar rats,weighing about 180 ~ 200 g.The rats were randomly divided into normal control group(n = 12)and model group(n = 34).After 7 days of adaptive feeding,fasted for 12 hours.Rats in the model group were injected intraperitoneally with streptozotocin(65 mg / kg).The normal control group was injected with the same dose of citrate buffer.72 hours after blood glucose test,blood glucose greater than 16.7 mmol / L,modeling success.The successful rats were divided into DCM group and DIZE treatment group.After 12 weeks of feeding,the treatment group was given DIZE 15 mg /kg /d,and the DCM group was given the same amount of normal saline for 4 weeks.16 weeks ultrasound testing and anesthesia for myocardial tissue 2.Blood glucose and weight measurement in rats:Before and after modeling respectively body weight and blood glucose were measured.3.Cardiac function test:At the end of 16 th week,intraperitoneal injection of 10% chloral hydrate 3ml / kg anesthesia,the heart function of each group was detected by ultrasound.4.The levels of Ang ? and Ang(1-7)in myocardium were detected by ELISA kit.5.Masson staining observed myocardial fibrosis 6.Immunohistochemical staining:Paraffin sections,collegen ?,collegen?,CTGF and IL-1,IL-6immunohistochemical staining.7.Real-time PCR: Collegen ?,collegen ?,CTGF gene fluorescence quantitative detection.8.Western blotting(Western blot):The total protein was extracted from the myocardium of rats and the expression of ACE2 protein,ERK1 / 2 pathway were detected by electrophoresis.Results: ACE2 protein expression in myocardial tissue of DIZE treatment group was significantly increased,Ang ? level decreased,Ang-1-7 content increased.Collagen content,L-1,and IL-6 in DIZE treatment group were significantly lower than those in diabetic group.Compared with the normal group,the E / A,EF and FS in diabetic cardiomyopathy group decreased significantly,and the E / A,EF and FS in DIZE treatment group were significantly improved compared with DCM group.Compared with the N group,the ERK phosphorylation level was significantly increased in DCM group,the treatment group was reduced.Conclusion:The ACE2 endogenous agonist acetylglycine diazanamid significantly enhances the activity of ACE2 and activates the ERK1 / 2 through the regulation of ACE2-Ang(1-7)-Mas axis to improve cardiac function in diabetic rats and inhibit the development of myocardial fibrosis,inflammation and apoptosis.Thus play a protective role on cardiac function in diabetic cardiomyopathy rats.