Inhibition Effect and Mechanism of Ursolic Acid on Myocardial Injury in GK Rats with Spontaneous Type 2 Diabetes Mellitus

The objective was to investigate the protective effect of Ursolic Acid (UA) on the myocardium of spontaneous type 2 diabetic GK rats and its possible mechanism. Male GK rats were randomly divided into low dose UA group (L-UA, 40 mg.kg(-1).d(-1)), high dose UA group (H-UAUA, 80mg.kg(-1).d-(1)) and model group (MC), and homologous wister rats were set as the normal control group, with 10 rats in each group. Each group was given orally once a day for 8 weeks. Fasting glucose, heart mass index and heart function were measured at 8 weeks after administration. After the death of rat in 8 weeks, detect myocardial tissue middle-late glycosylation end-products: creatine phosphate enzymes - analogous enzymes MB (CK-MB), nuclear factor kappa B predominate (nf-kappa B), tumor necrosis factor alpha and interleukin 2 (TNF-alpha), interleukin 2, IL-2) content with enzyme-linked immunosorbent assay method, and measure myocardial tissue nf-kappa B, TNF-alpha and IL-2 protein expression by using Western Blot method - combined with computer image analysis technology. The pathological changes of myocardial tissue were observed under light microscope, and the ultrastructure of myocardial tissue under electron microscope. Compared with the model control group, UA can effectively inhibit the pathological process of myocardial cell injury and myocardial fibrosis in GK rats and improve cardiac function. At the same time, UA can reduce the levels of AGEs, ck-mb, NF-kappa B, TNF-alpha and IL-2 in blood glucose and serum, and reduce the expression levels of NF-kappa B, TNF-alpha and IL-2 in rat myocardial tissue. UA has inhibitory effect on myocardial injury in type 2 diabetic rats, and its mechanism may be related to antagonistic NF-kappa B signal transduction pathway, inhibit transcriptional and/or post-transcriptional levels of TNF-alpha and IL-2, effectively control inflammatory response and delay myocardial cell apoptosis.