| Background:Renal ischemia followed by reperfusion is a common pathological physiology in clinical procedures of urology. It is a variety of factors involved in the process of renal transplantation, partial nephrectomy, renal wedge resection, renal pelvis joint incision of renal parenchyma, hemorrhagic shock and aortic repair. The blood perfusion of renal tissue is very rich, and it is very sensitive to ischemia and ischemia-reperfusion injury. If the renal tissue ischemia time is too long, it can not only lead to acute renal tubular necrosis and/or acute renal insufficiency, but also the important reason of abnormal renal function after renal transplantation and influencing the recovery of renal function. Related studies have shown that renal IRI is a risk factor for renal tissue survival time after renal transplantation. The incidence and mortality of the related diseases caused by renal ischemia reperfusion injury are continuously increasing. Therefore, how to effectively intervene renal damage caused by renal IRI and protect the renal function attracts more and more attention, to exploring the renal IRI is still an important problem in the field of urology. The pathogenesis of renal IRI is complex and has not been fully elucidated at present. The current study shows that the pathophysiological mechanism of renal ischemia reperfusion injury may be related to the production of large numbers of oxygen free radicals, the reaction of inflammation medium, Ca2+ overload and cell apoptosis, and so on. Nesfatin-1 is a kind of neural polypeptide substance secreted by hypothalamus, which plays a very important role in the process of energy balance and metabolism. Studies confirmed that nesfatin-1 has a variety of biochemical and physiological functions, which are involved in various pathophysiological processes in different human diseases and animal models. The present studies have shown that nesfatin-1 has been applied in the animal models and has certain protective effects, such as myocardial ischemia reperfusion injury, intestinal ischemia reperfusion injury, gastric mucosal injury, subarachnoid hemorrhage and traumatic brain injury. But there is no report about nesfatin-1 in the prevention and treatment of renal IRI. Therefore, we hypothesized that nesfatin-1 may have protective effect on renal ischemia reperfusion injury in rats. This research is to explore the protective effect on renal ischemia reperfusion injury, and its possible mechanisms.Objective:To evaluate the effects of nesfatin-1 on renal ischemia reperfusion injury in rats and explore its possible mechanism.Methods:24 male Wistar rats were purchased from the Hubei Provincial Academy of Preventive Medicine. The rats were randomly divided into three group (each consisting of eight rats):sham operation group (S group), renal ischemia reperfusion group (I/R group), and renal ischemia reperfusion+nesfatin-1 group (I/R+nesfatin-1 group). All rats expose renal pedicle, followed by a right nephrectomy. The left renal pedicle of I/R group and I/R+nesfatin-1 goup rats was occluded using a non-traumatic microvascular clamp for 45 min to effect complete cession of renal blood flow.Part ?:An automated analyzer (Siemens) was used to measure the levels of serum creatinine (Scr) and blood urea nitrogen (BUN), and the pathological changes of renal tissue were observed by PAS and HE staining.Part ?:To evaluate the effects of nesfatin-1 pretreatment on the role of the oxidative stress in renal ischemia reperfusion injury were detected by MDA levels, SOD, GSH and CAT activity.Part ?:To observe the effect of nesfatin-1 preconditioning on apoptosis pathway of renal ischemia reperfusion injury was evaluated by TUNEL, Caspase-3, Bcl2 and Bax expression.Part ?:To detection the effect of nesfatin-1 preconditioning on inflammation impact of renal ischemia reperfusion injury was determination of MPO, TNF-?, IL-10, IL-6 and nuclear factor kappa B (NF-?B) expression.Results:1?Topics of BUN and Scr test results showed that the I/R+nesfatin-1 group was obviously lower than that the I/R group (P<0.05), which indicated that nesfatin-1 pretreated can reduce the renal dysfunction.2?Under light microscopy, the morphological changes of the I/R+ nesftin-1 group were significantly improvement when compared with I/R group, and the pathological score was also significantly decreased (P<0.01), which indicated that nesfatin-1 preconditioning can alleviate the damage of renal tissue morphology caused by ischemia reperfusion injury.3?The results of oxidative stress pathway showed that the activity of SOD, CAT and GSH in I/R+nesfatin-1 group was significantly increased compared with that of I/R group (P<0.01), while the levels of MDA was significantly reduced (P<0.01), indicating that nesfatin-1 pretreatment can increased oxygen free radical scavenging enzymes of SOD, CAT, and GSH activity, to make the increased number of oxygen free radical when the renal IRI was cleared, thus reduce the levels of oxygen free radicals, eventually decrease the MDA expression.4?The results of apoptosis pathway showed that the expression of TUNEL in I/R+nesfatin-1 group was significantly decreased compared with the I/R group (p< 0.05), and further evaluated the expression of Caspase-3, Bcl-2, Bax, and the ratio of Bcl2/Bax, found that the expression of Caspase-3 and Bax in I/R+nesfatin-1 group decreased significantly (p< 0.01), the expression of Bcl2 increased significantly (p< 0.01), while the ratio of Bcl2/Bax was significantly increased (p<0.05), suggesting that the apoptosis cells of I/R+nesfatin-1 group was decreased. These results indicated that nesfatin-1 pretreatment could reduce the occurrence of apoptosis in renal ischemia reperfusion injury.5?The results of inflammation response showed that the expression of MPO, TNF-?, IL-1?, IL-6, and NF-KB in I/R+ nesfatin-1 group was significantly decreased, suggested nesfatin-1 preconditioning can ameliorates inflammation response in renal ischemia reperfusion injury.Conclusion:1?The results demonstrated nesfatin-1 preconditioning can ameliorates renal function on acute renal ischemia reperfusion injury in rats, and can reduce the damage of renal tissues.2?Nesfatin-1 pretreatment has a significant antioxidant effect on renal ischemia reperfusion injury through increased the SOD, CAT and GSH activities, and decreased the MDA levels.3?Nesfatin-1 pretreatment has obvious anti-apoptotic effect on renal ischemia reperfusion injury, and the effect may be probably by inhibiting the cell apoptosis, and upregulation the expression of antiapoptotic genes.4?Nesfatin-1 preconditioning inhibits the inflammatory reaction of neutrophils activation in renal ischemia reperfusion injury, and inhibits the release of inflammatory factors, thus reduce the inflammatory response and protecting renal IRI in rats. |
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