calpain-1在辛伐他汀抑制糖尿病大鼠心肌炎症中的作用

Role of calpain-1 in the inhibition of simvastatin on myocardial inflammation in diabetic rats

目的探讨钙蛋白酶-1(calpain-1)在辛伐他汀抑制糖尿病大鼠心肌炎症中的作用。方法40只SD大鼠随机分为4组:空白对照组(CON组)、链脲佐菌素组(STZ组)、辛伐他汀高剂量(20 mg/kg)治疗组(STZ+SIM20组)及低剂量(10 mg/kg)治疗组(STZ+SIM10组),给药12周后,采用HE染色观察心肌组织病理学改变;免疫组化检测心肌组织p65的表达;Western Blot检测心肌组织calpain-1、p65、IκBα的蛋白表达;ELISA检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的含量。结果辛伐他汀治疗组与STZ组相比,心肌细胞排列整齐,炎性细胞浸润减少;胞浆p65、IκBα蛋白表达增加,calpain-1、TNF-α、IL-6、核内p65表达减少。结论辛伐他汀对糖尿病大鼠心肌炎症有保护作用,其机制可能与抑制心肌calpain-1表达有关。

Objective To investigate the role of calpain-1 in the inhibition of simvastatin on myocardial inflammation in diabetic rats. Methods Forty SD rats were randomly divided into 4 groups:blank control group(CON group), streptozotocin group(STZ group), simvastatin high dose(20 mg/kg)treatment group(STZ+SIM20 group) and low dose(10 mg/kg) treatment group(STZ+SIM10 group). After 12 weeks, the pathological change of myocardial tissue was observed by HE staining. The expression of p65 was detected by immunohistochemistry. The expression of calpain-1, p65 and IκBα was detected by Western Blot.Serum TNF-α, IL-6 content was detected by ELISA. Results Compared with the STZ group, the SIM treatment group had neatly arranged cardiomyocytes and decreased inflammatory cell infiltration. The expression of p65 and IκBα protein in the cytoplasm was increased, and the expression of calpain-1, TNF-α,IL-6 and nucleus p65 in the nucleus was decreased. Conclusion Simvastatin has a protective effect on myocardial inflammation in diabetic rats, and its mechanism may be related to the inhibition of myocardial calpain-1 expression.