丹蛭降糖胶囊对肥胖大鼠骨骼肌IRE1α-JNK信号通路的干预效应

Intervention effect of Danzhi Jiangtang Capsule in IRE1α-JNK signaling pathway of skeletal muscle in obese rats

目的探讨丹蛭降糖胶囊对高脂饮食诱导的肥胖大鼠骨骼肌内质网应激(ERs)相关因子肌醇需求激酶1α(IRE1α)、磷酸化IRE1α(p-IRE1α)、c-jun氨基末端激酶(JNK)、磷酸化JNK(p-JNK)表达的影响。方法 30只雄性SD大鼠随机分为普通饮食组(NC组)、单纯高脂饮食组(HF组)、高脂饮食+丹蛭降糖胶囊组(FD组),每组各10只。应用全自动生化分析仪测定骨骼肌三酰甘油(TG)含量;Western blot检测骨骼肌组织IRE1α、p-IRE1α、JNK、p-JNK的蛋白表达水平。结果 1NC组、HF组以及FD组骨骼肌内TG含量分别为(1.87±0.72)、(3.03±0.71)、(2.71±0.58)μmol/g。与NC组比较,HF组大鼠骨骼肌TG含量显著增高(P=0.005);与HF组比较,FD组大鼠骨骼肌TG含量明显下降(P=0.024)。2Western blot检测结果显示,HF组p-IRE1α/IRE1α及p-JNK/JNK较NC组明显升高(P<0.05);FD组p-IRE1α/IRE1α及p-JNK/JNK较HF组明显降低(P<0.05)。3Pearson相关性分析发现,大鼠骨骼肌TG含量与HOMA-IR、p-IRE1α/IRE1α及p-JNK/JNK均呈正相关(r=0.63、0.66、0.57,均P<0.01)。结论丹蛭降糖胶囊可减轻骨骼肌脂质沉积,调节ERs相关IRE1α-JNK通路,从而改善骨骼肌胰岛素抵抗。

Objective To investigate the effect of Danzhi Jiangtang Capsule on the expressions of endoplasmic reticulum stress（ERs） related factors including IRE1α, p-IRE1α, JNK and p-JNK in skeletal muscle in obese rats fed with high-fat diet. Methods 30 Male Sprague-Dawley rats were randomly divided into basal diet group（NC group, n = 10）,untreated high-fat diet group（HF group, n = 10）, high-fat diet plus Danzhi Jiangtang Capsule（FD group, n = 10）. The contents of triglyceride in skeletal muscle were measured by automatic biochemical analyzer, and protein expression of IRE1α, p-IRE1α, JNK and p-JNK were determined by Western blot analysis. Results 1The contents of triglyceride in skeletal muscle in the NC group, HF group and FD group were（1.87±0.72）,（3.03±0.71）,（2.71±0.58） μmol/g, respectively.Compared with the NC group, the contents of triglyceride in skeletal muscle in the HF group were reduced significantly（P = 0.005）. In addition, the content of triglyceride in skeletal muscle in the FD group was significantly higher than that in the NC group（P = 0.024）. 2Western blot analysis revealed that p-IRE1α/IRE1α and p-JNK/JNK in skeletal muscle in the HF group were significantly higher than those in the NC group（P〈0.05）. Compared with the HF group, p-IRE1α/IRE1α and p-JNK/JNK in skeletal muscle of the FD group were decreased significantly（P〈0.05）. 3Pearson correlation analysis showed that the contents of triglyceride in skeletal muscle were positive correlated with HOMA-IR, p-IRE1α/IRE1α and p-JNK/JNK（r = 0.63, 0.66, 0.57, all P〈0.01）. Conclusion Danzhi Jiangtang Capsule can reduce lipid deposition in skeletal muscle, regulate ERs related IRE1α-JNK signaling p athway, thus improve skeletal insulin resistance.