AT1受体自身抗体调控肾组织内质网应激在糖尿病肾病发病中的机制研究  

Study on mechanisms of AT1 receptor autoantibodies for regulating renal tissue endoplasmic reticulum stress in diabetic nephropathy onset

作　　者：郭乃凤[1] 陈晓岚[1] 曹英杰[1] 袁莉[1] 范亚平[1] GUO Naifeng;CHEN Xiaolan;CAO Yingjie;YUAN Li;FAN Yaping(Department of Nephrology,Affiliated Hospital of Nantong University,Nantong,Jiangsu 226001,China)

机构地区：[1]南通大学附属医院肾内科,江苏南通226001

出　　处：《重庆医学》2019年第3期374-376,381,共4页Chongqing medicine

基　　金：国家自然科学基金资助项目(81170656)

摘　　要：目的研究AT1受体自身抗体(AT1-AA)调控肾组织内质网应激诱导大鼠糖尿病肾病的机制。方法构建糖尿病肾病模型大鼠为实验组,以正常大鼠为阳性对照组,以正常大鼠静脉注射AT1-AA作为AT1-AA处理组。使用ELISA法检测大鼠血清中AT1-AA表达变化;进一步使用HE染色法观察3组大鼠肾组织变化;使用Western blot检测各组大鼠肾组织葡萄糖调节蛋白-78(GRP78)及CCAAT/增强子结合蛋白同源蛋白(CHOP)表达水平。结果实验组大鼠血清中空腹血糖(FBG)、肾脏肥大指数(KHI)、转化生长因子β1(TGF-β1)、胰岛素样生长因子1(IGF-1)表达水平均高于正常大鼠(P<0.01),糖尿病肾病大鼠造模成功。与阳性对照组相比,实验组大鼠血清FBG、KHI、TGF-β1、IGF-1表达增加(P<0.01)。实验组和AT1-AA处理组肾组织中GRP78、CHOP蛋白表达水平均高于阳性对照组,差异有统计学意义(P<0.01)。结论糖尿病个体中AT1-AA通过调节GRP78、CHOP信号通路,增加肾组织内质网应激,从而诱导糖尿病肾病的发生、发展。Objective To study the mechanisms of AT1 receptor autoantibodies(AT1-AA)for regulating renal tissue endoplasmic reticulum stress induced rat diabetic nephropathy.Methods The diabetic nephropathy model was established as experimental group,and the normal rats were selected as the control group.Normal rats were injected with AT1-AA intravenously as AT1-AA group.The expression of AT1-AA in rat serum was detected by ELISA.The HE staining was used to observe the renal tissue changes of the rats of three group.The expressions of glucose-regulated protein-78(GRP78)and CCAAT/enhancer protein homolog protein(CHOP)expression levels in renal tissues of each group were detected by western blot.Results The expression levels of FBG,KHI,TGF-β1 and IGF-1 of experimental group were higher than those in control group(P<0.01),and the rat diabetic nephropathy were successfully modeled.At the same time,the levels of FBG,KHI,TGF-β1 and IGF-1 of experimental group increased compared with those in the control group(P<0.01).The expression levels of GRP78 and CHOP in experimental group and AT1-AA group were significantly higher than those in normal rat renal tissues,and the differences were statistically significant(P<0.01).Conclusion AT1-AA in diabetic individuals could increase the renal endoplasmic reticulum stress by regulating GRP78 and CHOP signaling pathways,there by inducing the development of diabetic nephropathy.

关 键 词：糖尿病肾病 AT1受体自身抗体 内质网应激 

分 类 号：R692.3[医药卫生—泌尿科学]