Rapamycin induces autophagy to alleviate acute kidney injury following cerebral ischemia and reperfusion via the mTORC1/ATG13/ULK1 signaling pathway

Su,Yang; Lu,Jingxiao; Gong,Pian; Chen,Xianguo; Liang,Chaozhao; Zhang,Jie

doi:10.3892/mmr.2018.9586

Rapamycin induces autophagy to alleviate acute kidney injury following cerebral ischemia and reperfusion via the mTORC1/ATG13/ULK1 signaling pathway

Authors:
- Yang Su
- Jingxiao Lu
- Pian Gong
- Xianguo Chen
- Chaozhao Liang
- Jie Zhang
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Affiliations: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: October 24, 2018 https://doi.org/10.3892/mmr.2018.9586
Pages: 5445-5454
Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute kidney injury (AKI) is a clinically common and severe complication of ischemia‑reperfusion (I/R), associated with high morbidity and mortality rates, and prolonged hospitalization. Rapamycin is a type of macrolide, primarily used for anti‑rejection therapy following organ transplantation and the treatment of autoimmune diseases. Rapamycin has been identified to exert a protective effect against AKI induced by renal I/R as an autophagy inducer. However, whether rapamycin preconditioning may relieve AKI following cerebral I/R (CIR) remains to be fully elucidated. The purpose of the present study was to investigate the effects of CIR on the renal system of rats and the role of rapamycin in AKI following CIR. In the present study, a CIR model was established in Sprague‑Dawley rats via a 90‑min period of middle cerebral artery occlusion and 24 h reperfusion, and pretreatment with an intraperitoneal injection of rapamycin (dosage: 1 mg/kg; 0.5 h) prior to CIR. The levels of serum creatinine and blood urea nitrogen (BUN), and the expression of inflammation‑, apoptosis‑ and autophagy‑associated markers were subsequently measured. In addition to certain histopathological alterations to the kidney, it was identified that CIR significantly increased the levels of serum creatinine, BUN, tumor necrosis factor‑α and interleukin‑1β, and significantly induced apoptosis and autophagy. It was observed that rapamycin induced autophagy through the mammalian target of rapamycin complex 1/autophagy‑related 13/unc‑51 like autophagy activating kinase 1 signaling pathway, and that rapamycin pre‑treatment significantly improved renal function and alleviated renal tissue inflammation and cell apoptosis in rats following CIR. In conclusion, the results suggested that rapamycin may alleviate AKI following CIR via the induction of autophagy.

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