基础医学与临床2024，Vol.44Issue(1)：31-36,6.DOI:10.16352/j.issn.1001-6325.2024.01.0031
雷帕霉素减轻碘佛醇诱导的模型大鼠急性肾损伤
Rapamycin attenuates ioversol-induced acute kidney injury in rat models
摘要
Abstract
Objective To investigate the role of autophagy in contrast-induced acute kidney injury(CI-AKI)in rats and to explore its possible mechanism.Methods SD rats were randomly divided into control group,acute kid-ney injury model group(intravenous injection of contrast medium ioversol via tail vein;model),rapamycin(RAPA)group and hydroxychloroquine(HCQ)group.Blood urea nitrogen(BUN)and serum creatinine(Scr)con-tents were measured and the potential change foun in renal pathology was detected by HE staining and microscopy.Transmission electron microscopy was used to observe auto-phagy-related changes in ultrastructure.Western blot was used to observe the expression of microtubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3Ⅰ,ubiquitin-binding protein p62 and Histone deacetylase 4(HDAC4).The expression of HDAC4 was also observed by RT-qPCR.Results Compared with control group,the level of BUN,Scr and HDAC4 expression in the model and HCQ group was increased(P＜0.01),the proximal tubules of the kidney were significantly damaged.In the model group,auto-phagososomes and autolysosomes increased,accompanied by an increase of LC3Ⅱ/LC3Ⅰ and a decrease in the p62 level(P＜0.05,P＜0.01);Compared with model group,there were more autophagosomes and autolysosomes were found in RAPA group(P＜0.01),accompanied by increased LC3Ⅱ/LC3Ⅰratio and decrease in the p62 and HDAC4(P＜0.05,P＜0.01).In contrast,the number of autophagy related structures decreased in HCQ group(P＜0.01),accompanied by the simultaneous increase of LC3Ⅱ/LC3Ⅰ,p62 and the increase of HDAC4(P＜0.01).Conclusions Ioversol may induce autophagy activation,while enhancing autophagy by RAPA alleviates CI-AKI induced renal dysfunction.The mechanism is potentially atributed to the regulation of HDAC4.关键词
碘佛醇/急性肾损伤/自噬/组蛋白去乙酰化酶4Key words
ioversol/acute kidney injury/autophagy/histone deacetylase 4分类
医药卫生引用本文复制引用
李庆菊,于然,陈佳佳,陈皓瑜,宋坚,王万鹏..雷帕霉素减轻碘佛醇诱导的模型大鼠急性肾损伤[J].基础医学与临床,2024,44(1):31-36,6.基金项目
国家自然科学基金青年科学基金(81600549) （81600549）
江苏省卫生健康委指导性课题(Z2021059) （Z2021059）
淮安市自然科学研究计划(HABL202260) （HABL202260）
江苏护理职业学院医教融合科研发展专项基金(YJRH202201,YJRH202207,YJRH202206) （YJRH202201,YJRH202207,YJRH202206）
