Dexmedetomidine promotes the recovery of renal function and reduces the inflammatory level in renal ischemia-reperfusion injury rats through PI3K/Akt/HIF-1α signaling pathway

B.-Y. Li, Y. Liu, Z.-H. Li, X.-L. An, S.-S. Xiao, G.-K. Liu, J. Zhang

Department of Anesthesiology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing, China. zjjdmm@sina.com

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• Pharmacology

OBJECTIVE: To evaluate the protective effect of dexmedetomidine (Dex) against renal ischemia-reperfusion injury (RIRI) in rats through the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway.

MATERIALS AND METHODS: (1) A Sprague- Dawley rat model of RIRI was established. Thirty rats were divided into Sham group, injury (RIRI) group, and Dex treatment (RIRI + Dex) group. Serum was collected to detect renal function-related indexes, and the levels of serum inflammatory factors were examined via enzyme-linked immunosorbent assay (ELISA). (2) The kidney tissues were separated, and the degree of tissue damage was determined using immunohistochemical staining. (3) Ribonucleic acids (RNAs) were extracted from tissues, and the mRNA levels of inflammatory factors were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). (4) The protein expressions of Akt, phosphorylated (p)-Akt, PI3K, p-PI3K, and HIF-1α were detected via Western blotting.

RESULTS: Compared with those in RIRI group, the levels of blood urea nitrogen and creatinine declined (p<0.05), the synthesized mRNAs of inflammatory factors in the kidney tissues were reduced (p<0.05), the secreted serum inflammatory factors was also reduced (p<0.05), and the phosphorylation levels of Akt and PI3K and the HIF-1α level rose (p<0.05) in RIRI + Dex group.

CONCLUSIONS: Dex promotes the recovery of renal function and reduces the inflammatory level in RIRI rats through the PI3K/Akt/HIF-1α signaling pathway.

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