Ischemia-reperfusion is a common injury of clinical ischemic disease and surgical lesions. Ischemic postconditioning (IPO) improves the ability of organs subjected to ischemia to tolerate injury. However, renal IPO studies have been based on animal models. In order to gain insights into IPO-induced alterations at the cellular level, an in vitro model for IPO was designed using the rat proximal tubular cell line NRK-52 E. This model was established by placing NRK-52 E cells in ischemic conditions for 3 h, then exposing cells to three cycles of reperfusion for 10 min and finally to ischemic conditions for 10 min (postconditioning). The cells were cultured further in reperfusion conditions for 3, 6, 12 and 24 h. Flow cytometry and Hoechst were used to assess apoptosis. The protein expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, cleaved caspase-3 and caspase-8 were analyzed by western blotting. The results demonstrated that apoptosis occurred in cells subjected to ischemia/reperfusion (I/R) alone or with postconditioning following reperfusion for 24 h. Cells subjected to I/R demonstrated increased expression of Bax, cleaved caspase-3 and caspase-8 at the end of reperfusion. However, the levels of Bax, cleaved caspase-3 and caspase-8 were significantly attenuated in cells, which had undergone IPO. In conclusion, apoptosis was observed in cells subjected to 3 h of ischemia-reperfusion injury and IPO was able to inhibit this apoptosis. IPO inhibited apoptosis by inhibiting the caspase pathway thereby exerting protective effects.

The aim of the present study was to investigate whether the diabetic kidney is more susceptible to ischemia/reperfusion (I/R) injury, and identify the potential mechanisms involved. An animal model of type 1 diabetes was created by treating rats with streptozotocin (STZ). This model was then used, along with healthy controls, to investigate the effect of diabetes mellitus (DM) on renal I/R injury. After 45 min of ischemia and 24 h of reperfusion, kidney and serum samples were acquired and used to evaluate function and histopathological injury in the kidneys. Western blotting was also used to determine the expression levels of key proteins. Rats experiencing renal I/R exhibited significant characteristics of renal dysfunction, reduced levels of Sirtuin 1 (SIRT1) protein (a key signaling protein in the kidneys), increased endoplasmic reticulum stress (ERS) and pyroptosis. Furthermore, diabetic rats exhibited further reductions in the levels of SIRT1 in response to renal I/R injury and an increase in the levels of ERS. These effects were all alleviated by the administration of a SIRT1 agonist. The present analysis revealed that the SIRT1‑mediated activation of ER stress and pyroptosis played a pivotal role in diabetic rats subjected to renal I/R injury. Downregulation of the SIRT1 signaling pathway were exacerbated in response to renal I/R injury‑induced acute kidney injury (AKI). The present data indicated that DM enhanced ER stress and increased pyroptosis by downregulating the SIRT1 signaling pathway.