Protective effect of renal ischemic postconditioning in renal ischemic-reperfusion injury

BACKGROUND: Renal ischemic postconditioning (RIPo) can protect the kidney from renal ischemia/reperfusion injury (RIRI). However, the underlying molecular mechanisms for RIPo in renal protection remained elusive. This study aimed to investigate the renoprotective effects of RIPo in an RIR rat model. METHOD: The Sprague Dawley (SD) rats were randomly divided into three groups respectively: sham group, the RIRI group and the RIPo group. The levels of proteinuria, blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), superoxide dismutase (SOD), lactate dehydrogenase (LDH), reactive oxidative species (ROS), interleukins (IL)-6, IL-1β, and IL-18 were measured by ELISA. Apoptotic cells and caspase-3 positive cells were detected by TUNEL assay and immunohistochemistry, respectively. The protein expressive levels of caspase-3, caspase-9, ATG8, Beclin1, p62, LC3-II, P-P13K, P-AKT and P-mTOR were detected by western blot. RESULTS: Our results showed that pretreatment with RIPo significantly reduced ischemic pathological and morphological changes. The levels of proteinuria, BUN, and Cr were also significantly reduced by RIPo pretreatment. Besides, ATG8, LC3-II and Beclin-1 were upregulated in the RIPo group, but p62 was downregulated. Moreover, RIPo pretreatment resulted in higher levels of phosphorylated PI3K, Akt, and mTOR. These results showed that RIPo protects the kidneys of rats from IRI with suppressed apoptosis and activated autophagy. Mechanically, the activated PI3K/AKT/mTOR signaling pathway were activated. CONCLUSIONS: Collectively, our data demonstrated that RIPo could suppress Inflammatory response, oxidative stress, apoptosis and induce autophagy as well as activate the PI3K/AKT/mTOR pathway, which may play an important role in renal protection against RIRI.