摘要
目的探究利拉鲁肽联合吡格列酮对糖尿病肾病大鼠肾组织细胞内质网应激及细胞凋亡的作用及机制。方法50只SPF级SD大鼠随机分为对照组(Control组)、糖尿病肾病组(DN组)、利拉鲁肽组(Liraglutide组)、吡格列酮组(Pioglitazone组)和利拉鲁肽联合吡格列酮组(Liraglutide+Pioglitazone组),每组10只;全自动生化分析仪检测大鼠24h尿蛋白及血清BUN和SCr水平;HE染色观察大鼠肾组织病理学改变;TUNEL检测大鼠肾组织细胞凋亡水平;Western blot检测大鼠肾组织细胞凋亡相关蛋白Bax和Bcl-2、内质网应激相关蛋白GRP78、ATF6、CHOP、p-PERK和p-EIF2α及NRF2/HO-1信号通路相关蛋白NRF2和HO-1表达水平。结果利拉鲁肽联合吡格列酮降低糖尿病肾病大鼠24h尿蛋白及血清BUN和SCr水平,改善大鼠肾组织病理学损伤,降低肾组织细胞凋亡水平,降低肾组织Bax、GRP78、ATF6和CHOP蛋白表达水平及PERK和EIF2α蛋白磷酸化水平,增加Bcl-2、NRF2和HO-1蛋白表达水平。结论利拉鲁肽联合吡格列酮治疗通过激活NRF2/HO-1信号通路抑制糖尿病肾病大鼠肾组织细胞内质网应激及细胞凋亡。
Objective To explore the effect and mechanism of liraglutide combined with pioglitazone on endoplasmic reticulum stress and apoptosis of renal tissue cells in diabetic nephropathy rats.Methods Fifty SPF SD rats were randomly divided into control group,diabetic nephropathy group(DN group),liraglutide group,pioglitazone group and liraglutide combined with piraglitazone group(Liraglutide+Pioglitazone group),with 10 in each group.The levels of urine protein in 24 hours and the levels of BUN and SCr in serum were detected by automatic biochemical analyzer.Histopathological changes of rat kidney were observed by HE staining.The apoptosis of renal cells in rats was detected by TUNEL.The expressions of apoptosis related proteins Bax and Bcl-2,endoplasmic reticulum stress related proteins GRP78,ATF6,CHOP,p-PREK and p-EIF2αand NRF2/HO-1 signaling pathway related proteins NRF2 and HO-1 in rat kidney tissues were detected by Western blot.Results Liraglutide combined with pioglitazone reduced the levels of 24-hour urine protein and the levels of BUN and SCr in serum,improved renal histopathological injury,reduced the level of apoptosis in renal tissue,and decreased the expressions of Bax,GRP78,ATF6 and CHOP,and the phosphorylation levels of PERK and EIF2α,increased the expressions of Bcl-2,NRF2 and HO-1 in diabetic nephropathy rats.Conclusion Liraglutide combined with pioglitazone inhibited endoplasmic reticulum stress and cell apoptosis in diabetic nephropathy rats by activating NRF2/HO-1 signaling pathway.
作者
张德鱼
刘艾芹
于磊
ZHANG De-yu;LIU Ai-qin;YU Lei(Department of Nephrology,Inner Mongolia Autonomous Region People's Hospital,Hohhot 010017,China)
出处
《解剖科学进展》
CAS
2022年第6期681-685,共5页
Progress of Anatomical Sciences
基金
内蒙古自治区科技厅科技计划项目(201702118)
作者简介
通信作者:张德鱼
