Effect of irbesartan on the MAPKs signaling pathway and related factors in myocardial injury of diabetic rats

ObjectiveTo observe the effects of irbesartan on myocardial injury in diabetic rats, and to explore the effect of irbsartan on MAPKs signaling pathway and related factors expression.

MethodsFifty male SD rats were randomly divided into the four weeks of diabetes (DM4W) group, eight weeks of diabetes(DM8W) group, eight weeks of diabetes + irbesartan(DM8W+Ir) group, control(Con) group and high sugar and cholesterol diet(HC) group(10 rats in each group).After the model of type 2 diabetic rats were successfully established, the DM8W+Ir group was administered using irbesartan solution by gavage.At the fourth week of feeding, the DM4W group was sacrificed, and heart tissue specimens were collected.After 8 weeks of feeding, the remaining rats were sacrificed.The fasting blood glucose(FBG), body weight(BW), heart to body ratio(H/B) and left ventricular mass index(LVWI) were compared among five groups.The Masson staining was used to observe the changes of myocardial fibrosis in isolated rat myocardium.The levels of IL-1β, IL-6, IL-1 and IL-1 were detected using ELISA.Western blotting was used to detect the expression levels of mitogen-activated protein kinase-1(MKP-1), P38 mitogen-activated protein kinase(P38MAPK) and extracellular signal-related kinases(P-ERK1/2) in myocardium.

ResultsThere was no statistical significance in the levels FBG, BW, H/B, LVWI, IL-1β, IL-6 and IL-1, MKP-1, and protein levels of P38MAPK, P-ERK1/2 between HC group and Con group(P>0.05).Compared with the Con group and HC group, the fibrotic changes of Masson staining myocardial cells were observed, the body weight lightened, the expression levels of inflammatory cytokines IL-1, IL-6 and IL-1 in myocardial cells increased, the protein expression levels of MKP-1 in myocardial tissues decreased, and the protein expression levels of P38MAPK and P-ERK1/2 increased in diabetic rats(P < 0.05 to P < 0.01).Compared with the DM4W and DM8W groups, the expression levels of IL-1 β, IL-6 and IL-1 decreased, the expression level of MKP-1 protein increased, and the expression levels of P38MAPK and P-ERK1/2 decreased in DM8W+Ir group(P < 0.05 to P < 0.01).

ConclusionsIrbesartan can improve the diabetic myocardial injury by regulating the MAPKs signaling pathway.