Simvastatin prevented myocardium of diabetes rats from apoptosis through inhibition of oxidative stress

Abstract

To investigate the protective effects and the possible mechanisms of simvastatin on myocardial injury induced by diabetes. Twenty-four SD rats (180~220)g were randomly divided into control group (control, n=8) and modeled groups(n=16), the modeled groups were injected with streptozotocin intraperitoneally to induce diabetes. Then the modeled rats were randomly divided into diabetes mellitus group (DM group, n=8) and diabetes mellitus + simvastatin group (DM+S group, n=8). Rats in DM+S group were treated with simvastatin at the dose of 40 mg/(kg·d)by gavage for 4 weeks, and the other two groups were treated with the same amount of saline. At the end of experiments, the heart tissues were collected for further observation. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in heart tissues were measured by spectrophotometry; HE staining of rat heart slides was used to observe the pathological changes; TUNEL assay was used to determine the apoptosis index of myocardial cells in each groups; The distribution of p53 in the heart tissues was evaluated by immunohistochemistry; Western blot was used to detect the expressions of p53, p53-phospho-serine 15, Bax and Bcl-2 in the heart tissues. ①Compared with control group, the content of malondialdehyde (MDA) was increased while the activity of superoxide dismutase (SOD) was decreased significantly in DM group (P<0.01). After simvastatin administration, the activity of SOD was increased and the content of MDA was decreased significantly (P<0.01). ② HE staining results showed that the myocardial cells in the DM group were disorganized, with unclear morphological structure and a large number of inflammatory cells infiltration. Compared with DM group, the myocardial morphology in DM+S group was improved significantly. ③TUNEL staining results showed that the apoptosis index of myocardial cells in DM group was increased significantly compared with that of control group, and the apoptosis index was decreased significantly after the treatment of simvastatin (P<0.01).④ Immunohistochemistry showed that compared with control group,the expression of p53 in DM group was increased significantly, and was expressed in both cytoplasm and nucleus, while the expression of p53 in DM+S group was decreased and the expression of p53 in nucleus was decreased significantly (P<0.01). ⑤ The results of Western blot showed that the expression levels of p53, p53-phospho-serine15 and Bax were higher than those in control group, and the expression of Bcl-2 was lower than that in control group (P<0.01). After simvastatin administration, the expression levels of p53,p53-phospho-serine 15 (P<0.01) and Bax were decreased significantly (P<0.05) and the expression of Bcl-2 was increased (P<0.05). Simvastatin exerted protective effects on myocardial injury caused by diabetes through improving the abnormal morphological changes of diabetic myocardium, alleviating oxidative stress and inhibiting apoptosis of myocardial cells. The mechanism is related to the regulation of apoptosis pathway mediated by p53.