褪黑素对糖尿病大鼠心肌细胞凋亡及MAPK通路的影响

目的 观察褪黑素(MLT)对2型糖尿病大鼠心肌损伤的保护作用及其抗凋亡机制.方法 24只雄性SD大鼠随机分为对照组、模型组、治疗组.采用链脲佐菌素(STZ) 25 mg/kg 腹腔注射诱导糖尿病大鼠模型,造模成功后开始给予MLT治疗24周.24周后,取心脏组织, HE染色检测心肌组织的形态变化,Masson染色检测心肌组织的胶原纤维的变化,原位末端标记法(TUNEL)检测心肌组织细胞凋亡的变化,Western blot检测其相关凋亡蛋白和丝裂原活化蛋白激酶(MAPK)通路相关蛋白的表达水平.结果 HE染色显示MLT能改善心肌组织形态的紊乱情况,Masson染色显示MLT能缓解心肌组织胶原纤维的堆积.与糖尿病大鼠比较,MLT能明显改善糖尿病大鼠心肌组织的细胞凋亡情况.Western blot显示MLT能下调凋亡蛋白Bax和caspase3的表达(P<0.05),上调抗凋亡蛋白Bcl-2的表达(P<0.05);此外,MLT也能明显下调p-JNK蛋白的表达(P<0.05).结论 MLT可能通过下调血糖、MAPK通路中p-JNK信号通路表达,改善糖尿病大鼠心肌组织的凋亡.

Effects of melotonin on myocardialapoptosis and MAPK pathway in diabetic rats

Objective To explore protective effects of melatonin(MLT) on myocardial in rats with type 2 diabetes and its potential mechanism.Methods 24 male SD rats were divided into control group, model group and treatment group randomly.In order to induce diabetes, rats were intraperitoneally injected with streptozocin.Then rats in treatment group were given MLT by gavage for 24 weeks.Finaly, hearts were collected.Haematoxylin-eosin(HE) staining and Masson staining were performed to observe the myocardial morphology change.TUNEL was used to observe myocardial apoptosis.Apoptosis-related protein and MAPK pathways related proteins were detected by Western blot.Results HE staining showed that MLT reversed the disarrangement of myocardial fibers.Masson staining displayed that MLT decreased the collagen deposition in cardiac tissue.Compared with model group, MLT could alleviate myocardial apoptosis in diabetic rats.Western blot showed that MLT decreased the expression of pro-apoptotic protein Bax and caspase3(P<0.05), and increased the expression of anti-apoptotic protein Bcl-2(P<0.05).Besides, MLT remarkably decreased the expression of p-JNK(P<0.05).Conclusion MLT maybe ameliorate apoptosis of myocardial cell through decreasing blood glucose and suppressing p-JNK/MAPK overexpression in diabetic rats.