杜仲黄酮对糖尿病小鼠胰腺线粒体功能的影响

Effects of Eucommia flavonoids on the function of pancreatic mitochondria in diabetic mice

目的:探讨杜仲黄酮对糖尿病小鼠胰腺线粒体功能的影响。方法:链脲佐菌素联合高脂高糖饮食共同诱导构建糖尿病小鼠模型。将40只糖尿病模型小鼠随机分为模型组、二甲双胍组和杜仲黄酮低、高剂量组,每组10只。另以10只健康昆明小鼠为空白对照组。末次给药2 h后检测各组空腹血糖(FBG)。采用酶联免疫吸附试验(ELISA)法检测血清胰岛素(FNS)、总抗氧化能力(T-AOC)含量,过氧化氢酶(CAT)、超氧化物歧化酶(SOD)活性,胰腺组织ATP酶、线粒体呼吸链ComplexI、ComplexIII活性及氧自由基(ROS)、ATP含量。Western blotting法检测胰腺组织中核呼吸因子1(NRF1)、线粒体融合蛋白1(Mfn1)蛋白表达量。结果:与模型组比较,杜仲黄酮高、低剂量组小鼠FBG水平显著下降,血清FNS、T-AOC含量及CAT、SOD活性增加(P<0.05或P<0.01);胰腺ATP含量增加,ROS含量减少,ATP酶、Complex I、ComplexⅢ活力增加(P<0.05或P<0.01);胰腺中NRF1、Mfn1蛋白表达增加(P<0.05或P<0.01)。结论:杜仲黄酮能改善胰腺组织线粒体功能,其作用机制可能为调节线粒体生物合成因子和融合因子的表达,提高胰腺的抗氧化能力及线粒体的呼吸功能,保障能量的供应,使胰岛素分泌增加,达到降血糖的作用。

Objective:To investigate the effects of eucommia flavonoids on the function of pancreatic mitochondria in diabetic mice.Methods:The diabetic mice model were established by tail vein injection of streptozotocin(STZ)combined with high-fat and high-glucose diet.The diabetic mice were divided into model control group,metformin group,low-dose and high-dose of eucommia flavonoids groups randomly.Another 10 healthy Kunming mice were used as the blank control group.After last administration,the fasting blood glucose(FBG)of mice fasted over 2 hours were detected,as well as the collection of serum and pancreas samples.The serum contents of insulin(FNS),total antioxidant capacity(T-AOC)and the activities of catalase(CAT),superoxide dismutase(SOD)were measured.The activities of ATPase,mitochondrial respiratory chain ComplexI,III and oxygen free radicals(ROS),ATP levels in pancreatic tissues were analyzed.The expressions of mitochondrial biosynthesis factor NRF1 and mitochondrial fusion factor Mfn1 in pancreas were determined by western blotting.Results:Compared with model control,the FBG was decreased in mice treated with eucommia flavonoids,and the activities of CAT,SOD and FNS,T-AOC levels were increased(P<0.05).In pancreas tissues,activities of ATPase,mitochondrial respiratory chain ComplexI,III and ATP levels were enhanced,the ROS level was in contrast(P<0.05 or P<0.01).In addition,the expressions of NRF1 and Mfn1 were up-regulated(P<0.05).Conclusion:The underlying mechanism of eucommia flavonoids on improving pancreatic mitochondrial function maybe associated with the modulation on mitochondrial biosynthesis factor and mitochondrial fusion factor,elevating the anti-oxidant capability of pancreas and the mitochondrial respiratory function,benefiting the energy supply and insulin secretion,resulting in hypoglycemia.