Rapamycin attenuates ioversol-induced acute kidney injury in rat models
10.16352/j.issn.1001-6325.2024.01.0031
- VernacularTitle:雷帕霉素减轻碘佛醇诱导的模型大鼠急性肾损伤
- Author:
Qingju LI
1
,
2
,
3
;
Ran YU
;
Jiajia CHEN
;
Haoyu CHEN
;
Jian SONG
;
Wanpeng WANG
Author Information
1. 南京医科大学康达学院附属医院 涟水县人民医院, 江苏 淮安 223400
2. 扬州大学医学院 临床学院 江苏省中西医结合老年病防治重点实验室, 江苏 扬州 225009
3. 江苏护理职业学院, 江苏 淮安 223400
- Keywords:
ioversol;
acute kidney injury;
autophagy;
histone deacetylase 4
- From:
Basic & Clinical Medicine
2024;44(1):31-36
- CountryChina
- Language:Chinese
-
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.
