Acute renal injury induced by endotoxic shock in rats is alleviated via PI3K/Nrf2 pathway

C.-H. Chuang, C.-K. Yang, P.-H. Wu, Y. Zhang, P.-J. Yang

Department of Emergency Medicine, Xiamen Changgung Hospital, Medical College of Xiamen University Teaching Hospital, Xiamen. flystar@gmail.com

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• Pharmacology

OBJECTIVE: To explore the effect of PI3K/Nrf2 pathway on acute kidney injury (AKI) induced by endotoxic shock in rats by construction of the endotoxic shock rat model.

MATERIALS AND METHODS: A total of 30 Sprague Dawley (SD) rats were randomly assigned into three group, namely the control group (group C), endotoxic shock model group (group L) and wortmannin + endotoxic shock model group (group WL), with 10 rats in each group. Pathological lesions in renal tissues were evaluated by histological score of kidney (HSK). Biochemical indicators including blood urine nitrogen (BUN), creatinine (Cr) and urinary α1-microglobulin (α1-MG) in renal tissues were accessed. Activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by relative commercial kits. Expression levels of Nrf2, Heme oxygenase 1 (HO-1) and Akt in renal tissues were determined by Western blot and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), respectively.

RESULTS: HSK, levels of BUN, Cr and α1-MG and activities of SOD and MDA were significantly increased in group L comparing to those in group C (p<0.05). The above-mentioned indicators were also remarkably higher in group WL than those of group L (p<0.05). There were significant differences in expression levels of Nrf2, HO-1 and Akt between group L and group WL (p<0.05). In particular, lower mRNA levels of Nrf2 and HO-1, as well as protein levels of p-Akt, Nrf2 and HO-1 were observed in group WL compared with those in group L (p<0.05).

CONCLUSIONS: The present study showed that AKI induced by endotoxic shock in rats was regulated through PI3K/Nrf2 pathway. HO-1 acts as the effector protein, might serve as an essential factor in protecting AKI induced by endotoxic shock.

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