Abstract: Objective: To study the effect of ursolic acid on cardiomyopathy in mice with diabetes induced by high-fat diet combined with low dose streptozotocin, and to explore its possible mechanism. Methods: Thirty male ICR mice were randomly divided into control group (n=10) and moulding group (n=20), the mice in the two groups were fed with regular diet and high-fat diet respectively for 6 weeks, and then the mice in the moulding group were injected with streptozotocin (30 mg/kg) for 5 successive days to induce diabetes mellitus (DM). Fasting blood glucose (FBG) was measured after 9 days. Mice with FBG over 11.1 mmol/L were regarded as DM. Twenty DM mice were randomly divided into model group and ursolic acid group (n=10). Mice in each group were continuously administrated ursolic acid (100 mg/kg) or corresponding solvent intragastrically for 8 weeks. After that, FBG was measured, body weight (BW), heart weight and left ventricular weight were weighed in order to calculate the heart mass index (HMI) and left ventricular mass index (LVMI). Levels of creatine kinase (CK), lactate dehydrogenase (LDH) in serum and the level of superoxide dismutase (SOD), malondialdehyde (MDA) in myocardial tissue were detected. HE staining was used to observe pathological changes of myocardial tissue. Immunohistochemistry was employed to determine the expression of NOD-like receptor protein 3 (NLRP3) and interleukin 1β (IL-1β). Results: Compared with the control group, HMI, LVMI were apparently enlarged, levels of FBG, CK, LDH in serum and MDA in myocardial tissue were extremely increased, while the activity of SOD in myocardial tissue were extraordinary decreased in diabetic group. HE staining of myocardium showed that arrangement disorder of myocardial fibers, edema and hypertrophy in myocardial cell, as well as inflammatory cell infiltration in model group. Immunohistochemistry showed that the expression of NLRP3 and IL-1β in myocardial tissue increased obviously in model group, the above changes inursolic acid group were significantly ameliorated. Conclusion: Ursolic acid has a obvious protective effect on myocardial injury in mice with diabetes induced by high-fat diet combined with low dose streptozotocin, and its mechanism may be associated with inhibiting NLRP3 inflammasome activation, reducing IL-1β generation and alleviating myocardial inflammatory injury.

Key words: ursolic acid, diabetic cardiomyopathy, inflammation, NLRP3, IL-1β, mouse