miR-141-3p调控缺血再灌注肾损伤小管上皮细胞焦亡  

Effects of miR-141-3p on pyroptosis of tubular epithelial cells in renal ischemia-reperfusion injury

作　　者：罗庆琳 邓军辉 田恩 谭微 林利容 郑卢权 曹增钢 杨聚荣 LUO Qinglin;DENG Junhui;TIAN En;TAN Wei;LIN Lirong;ZHENG Luquan;CAO Zenggang;YANG Jurong(Department of Nephrology,Third Affiliated Hospital of Chongqing Medical University(Gener Hospital),Chongqing 401120,China)

机构地区：[1]重庆医科大学附属第三医院(捷尔医院)肾内科,401120

出　　处：《免疫学杂志》2022年第11期928-935,943,共9页Immunological Journal

基　　金：重庆英才计划(cstc2021ycjh-bgzxm0090);国家自然科学基金(81770682)。

摘　　要：目的探讨miR-141-3p在缺血再灌注(ischemia reperfusion,I/R)诱导急性肾损伤(acute kidney injury,AKI)中的作用机制。方法建立缺血再灌注AKI小鼠模型及体外小鼠肾小管上皮细胞TCMK1缺氧复氧模型(hypoxia reoxygenation,H/R)。自动化学分析仪检测小鼠血清肌酐(Scr)和血清尿素氮(BUN),肾组织PAS染色评估肾脏病理损伤情况,蛋白印迹法检测焦亡关键蛋白(GSDMD,GSDMD-N,CASPASE-1)及炎症因子(IL-1β,IL-18)的表达,实时定量PCR检测miR-141-3p的表达。结果MiR-141-3p在缺血再灌注小鼠肾组织和缺氧复氧肾小管上皮细胞中表达显著增高(P<0.05)。体外过表达miR-141-3p能显著促进H/R诱导的GSDMD(P<0.05)、GSDMD-N(P<0.05)以及IL-18(P<0.05)表达,而敲低miR-141-3p能显著抑制H/R诱导的GSDMD-N(P<0.05)以及CASPASE-1(P<0.05)表达水平。结论MiR-141-3p可能通过促进肾小管上皮细胞焦亡介导小鼠肾脏缺血再灌注损伤。Acute kidney injury(AKI)is a clinical syndrome caused by various causes with rapid decline of renal function,in which ischemia-reperfusion(I/R)injury is one of the main causes.This study was designed to explore the role and mechanism of miR-141-3 p in AKI induced by I/R.A mouse model of ischemia-reperfusion AKI and an in vitro model of hypoxia reoxygenation(H/R)of mouse tubular epithelial cells(TCMK1)were established.Serum creatinine(Scr)and serum urea nitrogen(BUN)were measured by automated chemical analyzer;renal pathological injury was evaluated by PAS staining.Western blot was used to detect the expression of pyroptosis key proteins(GSDMD,GSDMD-N,CASPASE-1)and inflammatory factors(IL-1β,IL-18),while real-time quantitive PCR was used to detect the expression of miR-141-3 p.Data showed that miR-141-3 p expression was significantly increased in I/R mouse kidney tissues and hypoxia-reoxygenated renal tubular epithelial cells.In vitro overexpression of miR-141-3 p significantly promoted H/R-induced expression of GSDMD(P<0.05),GSDMD-N P<0.05)and IL-18(P<0.05).While knocking down miR-141-3 p could significantly inhibit the expression levels of GSDMD-N(P<0.05)and CASPASE-1(P<0.05)induced by H/R.In conclusion,miR-141-3 p may mediate renal ishchemia-reperfusion injury in mice by promoting pyroptosis of renal tubular epithelial cells.

关 键 词：急性肾损伤 缺血再灌注 缺氧复氧 miR-141-3p 细胞焦亡 

分 类 号：R692.6[医药卫生—泌尿科学]