硫辛酸调节糖尿病大鼠肾脏内质网应激、足细胞蛋白表达及JNK通路的实验研究  

Lipoic acid regulates endoplasmic reticulum stress,podocyte protein expression and JNK pathway in diabetic rats

作　　者：兰天[1] 刘巍梦 邹阳 邱平[1] LAN Tian;LIU Wei-meng;ZOU Yang(Department of Endocrine and Metabolism,The First Affiliated Hospital of Chengdu Medical College,Chengdu Sichuan 610500,China;Department of Gynecology,The Sixth People's Hospital of Panzhihua,Panzhihua Sichuan 617023,China;Department of Internal Medicine,Chongqing Ninth People's Hospital,Chongqing 400700,China)

机构地区：[1]成都医学院第一附属医院内分泌代谢科,四川成都610500 [2]四川省攀枝花市第六人民医院妇科,四川攀枝花617023 [3]重庆市第九人民医院内科,重庆400700

出　　处：《临床和实验医学杂志》2019年第21期2248-2251,共4页Journal of Clinical and Experimental Medicine

基　　金：2016年四川省卫生和计划生育委员会科研课题(编号:16PJ439)

摘　　要：目的研究硫辛酸对糖尿病大鼠肾脏内质网应激(ESR)、足细胞蛋白表达及JNK通路的调节作用。方法选择清洁级雄性SD大鼠36只并随机分为对照组、糖尿病组、硫辛酸组,每组12只。糖尿病组、硫辛酸组采用链脲佐菌素腹腔注射的方式建立糖尿病模型,硫辛酸组给予硫辛酸灌胃干预,对照组和糖尿病组给予等剂量生理盐水灌胃,每日1次,连续8周。比较三组干预后血糖、肾功能以及肾脏组织中ESR标志基因、足细胞蛋白、JNK信号通路分子表达的差异。结果糖尿病组大鼠的空腹血糖(FBG)、血肌酐(Scr)、24 h尿白蛋白(24 h UAlb)水平及肾脏中葡萄糖调节蛋白78(GRP78)、丝/苏氨酸跨膜蛋白激酶α(IRE1α)的m RNA表达水平、磷酸化C-Jun N-末端激酶(p-JNK)、转化生长因子-β1(TGF-β1)、含半胱氨酸的天冬氨酸蛋白水解酶3(caspase-3)、Ⅳ型胶原(Col-IV)的蛋白表达水平均明显高于对照组(P<0.05),肾脏中Podocin、CD2AP、Nephrin的蛋白表达水平均明显低于对照组(P<0.05),肾脏中PERK、ATF-6的m RNA表达水平与对照组比较无显著性差异(P>0.05);硫辛酸组大鼠的SCR、24 h UAlb水平及肾脏中GRP78、IRE1α的m RNA表达水平、p-JNK、TGF-β1、caspase-3、Col-IV的蛋白表达水平均明显低于糖尿病组,肾脏中Podocin、CD2AP、Nephrin的蛋白表达水平均明显高于糖尿病组(P<0.05),FBG水平及肾脏中PERK、ATF-6的m RNA表达水平与糖尿病组比较无显著性差异(P>0.05)。结论硫辛酸能够改善糖尿病大鼠的肾功能,且该效应与抑制内质网应激及JNK通路、增加足细胞蛋白表达有关。Objective To study the regulatory effects of lipoic acid on endoplasmic reticulum stress(ESR),podocyte protein expression and JNK pathway in diabetic rats.Methods 36 clean male SD rats were randomly divided into control group,diabetic group and lipoic acid group.Diabetic model was established by intraperitoneal injection of streptozotocin in diabetic group and lipoic acid group.Lipoic acid group was given intragastric intervention with lipoic acid.The control group and the diabetic group were given an equal dose of normal saline,once a day,8 weeks.The differences of blood sugar,renal function and expression of ESR marker gene,podocyte protein and JNK signaling pathway were compared among the three groups.Results The levels of fasting blood glucose(FBG),serum creatinine(Scr),24 h urinary albumin(24 h UAlb)and the mRNA expression of GRP78,IRE1αand the protein expression of p-JNK,TGF-β1,caspase-3,Col-IV in kidney of diabetic group were significantly higher than those in the control group.While the protein expression of Podocin,CD2AP and Nephrin in kidneys were significantly lower than those in the control group.The mRNA expression of PERK and ATF-6 in kidney had no significant difference with control group.The levels of FBG,SCR,24 h UAlb and the mRNA expression of GRP78,IRE1αand the protein expression of p-JNK,TGF-β1,caspase-3,Col-IV in kidney of lipoic acid group were significantly lower than those in diabetic group.The expression levels of Podocin,CD2AP and Nephrin in kidney were significantly higher than those in diabetic group.The FPG level and the mRNA expression of PERK and ATF-6 in kidney had no significant difference with diabetic group.Conclusion Lipoic acid can improve renal function in diabetic rats and this effect is related to inhibiting endoplasmic reticulum stress,JNK pathway and increasing podocyte protein expression.

关 键 词：大鼠 糖尿病 硫辛酸 内质网应激 足细胞 JNK 信号通路 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]