目的探讨α-硫辛酸(alpha lipoic acid,A-LA)对内质网应激(endoplasmic reticulum stress,ERS)介导的糖尿病大鼠心肌细胞凋亡的影响.方法 SD大鼠随机分为3组：对照组、糖尿病模型组、α-硫辛酸组.采用链脲佐菌素以60 mg/kg于左下腹腔一次性注射建立大鼠糖尿病模型.α-硫辛酸组按60mg/kg灌胃,对照组和糖尿病组每日给予等量0.9%氯化钠注射液灌胃.12周后检测血糖和心功能状态；原位末端转移酶标记技术(TdT-mediated dUTP nick end labeling,TUNEL)检测细胞凋亡；Western Blot和免疫组织化学法检测葡萄糖调节蛋白78(GRP78)与和半胱胺酸蛋白酶蛋白-12(Caspase-12)的蛋白表达水平.结果与对照组比较,糖尿病模型组大鼠血糖值明显增高(P<0.05),心功能受损；α-硫辛酸剂量组对糖尿病大鼠血糖和心功能有一定程度的改善.与对照组相比,糖尿病组大鼠心肌细胞凋亡明显增加(P<0.05),GRP78和Caspase-12蛋白表达增加.α-硫辛酸组心肌细胞凋亡明显降低,GRP78和Caspase-12蛋白表达有所减少.结论α-硫辛酸对糖尿病心肌组织具有保护作用,其机制可能与降低GRP78表达,拮抗Caspase-12,阻断ERS启动的凋亡通路有关.关键词：α-硫辛酸；糖尿病心肌病；内质网应激%Objective To study the effect of alpha lipoic acid(A-LA) on endoplasmic reticulum stress(ERS)-induced myocardial apoptosis in diabetic rats. Methods SD rats were randomly divided into control group, diabetic model group, and A-LA group. A diabetic model was established by intraperitoneal injection with streptozocin(60mg/kg). A-LA group underwent A-LA gastric irrigation(60 mg/kg). Control group and diabetic model group received daily normal saline gastric irrigation. Their blood sugar and cardiac function were tested after 12 weeks. Cell apoptosis was detected by TUNEL. Glucose-regulated expression levels of GRP78 and caspase-12 were measured by Western blotting and immunohistochemistry, respectively. Results The blood glucose level was significantly higher and the damage of cardiac function was severer in diabetic model group and A-LA group than in control group(P<0.05). The A-LA improved the blood glucose level and cardiac function of diabetic rats. The cell apoptosis level and the expression levels of GRP78 and caspase-12 were significantly higher in diabetic model group than in control group and significantly lower in A-LA group than in control group(P <0.05). Conclusion A-LA protects cardiac muscle in diabetic rats possibly by decreasing the expression level of GRP78 and caspase-12, and blocking the ERS-initiated opoptotic pathway.
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