慢性间歇性缺氧合并肥胖通过内质网应激导致小鼠肾脏损伤

Chronic intermittent hypoxia combined with obesity leads to mice renal damage through endoplasmic reticulum stress

目的 探讨慢性间歇性缺氧合并肥胖导致小鼠肾脏损伤的作用机制。方法 将C57BL/6小鼠随机分为正常对照组(RC组)、慢性间歇性缺氧组(RH组)、肥胖组(HC组)和慢性间歇性缺氧合并肥胖组(HH组)。血清肌酐、尿素氮试剂盒检测各组小鼠肾功能,HE染色观察肾脏形态,TUNEL染色观察肾小管上皮细胞凋亡,实时荧光定量PCR及Western blotting检测肾脏组织中内质网应激凋亡通路mRNA及蛋白表达。结果 与RC组比较,RH组、HC组、HH组小鼠血清肌酐、尿素氮水平均升高,肾脏形态结构均紊乱,其中HH组最显著(P<0.05)。与RC组比较,HH组凋亡细胞增多,内质网应激凋亡因子(肌醇需求酶1α、剪切后的X盒结合蛋白1、C/EBP同源蛋白、c-Jun氨基端激酶、cleaved-Caspase-3)mRNA或蛋白表达明显上调(P<0.05)。结论 慢性间歇性缺氧合并肥胖可能通过内质网应激凋亡途径诱导肾小管细胞凋亡,加重肾脏损伤。

Aim To investigate the effect and mechanism of chronic intermittent hypoxia combined with obesity in mice renal injury.Methods C57BL/6 mice were randomly assigned into normal control group(RC group),regular hypoxia group(RH group),hyperlipemia control group(HC group)and hypoxia combined with hyperlipemia group(HH group).The kits of serum creatinine and urea nitrogen were used to detect the renal function of mice in each group.HE staining was used to observe the renal morphology.TUNEL staining was used to observe the apoptosis of renal tubular epithelial cells.Real time fluorescent quantitative PCR and Western blotting were used to detect the mRNA and protein expression of endoplasmic reticulum stress apoptotic pathway in renal tissue.Results Compared with RC group,the levels of serum creatinine and urea nitrogen increased,and the morphological structure of kidney was disordered in RH group,HC group and HH group,especially in HH group(P<0.05).Compared with RC group,apoptosis cells increased in HH group,and the mRNA or protein expression of endoplasmic reticulum stress apoptosis factors(inositol-requring protein-1α,spliced X-box binding protein 1,C/EBP homologous protein,c-Jun N-terminal kinase,Caspase-3)were significantly up-regulated(P<0.05).Conclusion Chronic intermittent hypoxia combined with obesity may induce apoptosis of renal tubular cells through endoplasmic reticulum stress and aggravate renal injury.