Specific microRNAs are involved in the reno?protective effects of sevoflurane preconditioning and ischemic preconditioning against ischemia reperfusion injury in rats

摘要

The kidneys are prone to developing ischemia reperfusion injury (IRI) following certain renal surgeries and cardiovascular surgeries requiring cardiac arrest. Sevoflurane and ischemic preconditioning reportedly alleviate IRI, which is mediated via microRNAs. The present study compared anesthetic preconditioning (APC) and ischemic preconditioning (IPC) on microRNAs, which promote cell?survival pathways in rats in a randomized controlled study. After undergoing right nephrectomy under general anesthesia, male Wistar rats (336±24?g) and were divided into four groups (IRI, APC, IPC and sham; n=7 each). The IRI?group underwent 45?min clamping of the left renal vasculature, followed by 4?h of reperfusion. APC involved exposure to one minimum alveolar concentration sevoflurane for 15?min. IPC included three cycles of two?min clamping and five?min reperfusion. Blood and renal biopsy samples were assessed postoperatively to measure serum creatinine and to analyze renal microRNA (miR) expression using reverse transcription?quantitative polymerase chain reaction (RT?qPCR) testing and their target pathways with Ingenuity Pathway Analysis?. The present study found that serum creatinine values in APC (0.71±0.08?mg/dl) and IPC (0.73±0.1?mg/dl) groups were lower than in the IRI?group (0.96±0.13?mg/dl; P<0.05), indicating amelioration of IRI by APC and IPC. RT?qPCR followed by pathway analysis indicated that APC and IPC affect ‘protein kinase?B (Akt)’. APC promoted miR?17?3p and suppressed miR?27a. IPC promoted miR?19a. All the miRs were predicted to regulate phosphorylated Akt, which promotes cell?protection. Western blot analysis showed that expression of phosphorylated Akt increased and phosphatase and tensin homologue deleted from chromosome?10 (PTEN) decreased following APC and IPC. The present study concluded that APC and IPC affect different miRs, although they are estimated to similarly promote the PTEN/phosphoinositide 3?kinase/Akt signaling pathway, resulting in reno?protection.