α-硫辛酸对糖尿病大鼠内质网应激相关分子GRP78和Caspase-12表达的影响

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。

Effect of alpha lipoic acid on expression of endoplasmic reticulum stress-related molecules GRP78 and caspase-12 in diabetic rats

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.