Rapamycin attenuates ioversol-induced acute kidney injury in rat models

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 kidney 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) contents 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, autophagososomes 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/LC3Ⅰ ratio 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.

Keywords

• ioversol|acute kidney injury|autophagy|histone deacetylase 4