间歇性肾门阻断减轻糖尿病小鼠肾缺血再灌注损伤的作用研究OACSTPCD

Background Patients with renal tumor complicated with diabetes mellitus have a high incidence of chronic kidney disease after nephron sparing surgery(NSS),and lack of effective prevention and intervention in clinic.Objective To investigate the effect of diabetes mellitus on renal ischemia-reperfusion(IR)injury in mice under different warm ischemia time gradients and analyze the effect of intermittent renal hilum occlusion on reducing renal ischemia-reperfusion injury in diabetic mice.Methods Thirty-six nondiabetic male mice and thirty-six diabetic C57BL/6J male mice were randomly divided into ischemia reperfusion(IR)-15 minutes,IR-20,IR-25,IR-30,IR-35 minutes and sham group(n=6 for each group).Unilateral kidney ischemia-reperfusion injury mouse model was established,after 24 h reperfusion,the levels of acute kidney injury,apoptosis and oxidative stress injury were evaluated by functional,histological and immunological methods,and the effects of diabetes on renal IR injury in mice under different ischemic time points were analyzed.Eighteen C57BL/6J male mice were randomly divided into continuous hilar occlusion group,intermittent hilar occlusion group(15 minutes of ischemia followed by 5 minutes of reperfusion,15-5-15 minutes),and sham group(n=6 for each group).The levels of acute kidney injury,apoptosis and oxidative stress injury were assessed via functional and histological analysis after 24 h reperfusion.Results When the ischemia time was 15 min,no obvious renal function injury,pathological injury and oxidative stress injury were observed in diabetic mice and normal mice after operation;When the ischemia time was 20 min and 25 min,the indexes of renal function injury,pathological injury and oxidative stress injury in diabetic mice were higher than those in normal mice;When the ischemia time was 30 min and 35 min,the postoperative renal function and pathological injury of diabetic mice and ordinary mice were severe,and there was no significant difference between the two groups(P＞0.05).Compared with continuous renal hilum occlusion,intermittent renal hilum occlusion could reduce serum creatinine(P<0.001),acute tubular necrosis score(P<0.001),immunohistochemical NGAL semi quantitative score(P<0.001),TUNEL apoptosis score(P<0.001),malondialdehyde level(P<0.01)and restore catalase activity(P<0.001)at 24 h after operation.Conclusion Diabetes mellitus does not aggravate acute kidney injury after IR in mice with short ischemic time.After ischemia time exceeding 20 min,diabetes mellitus aggravates acute kidney injury after IR in mice.Intermittent renal hilum occlusion can significantly reduce the acute kidney injury after IR in diabetic mice and inhibit the occurrence of oxidative stress injury,suggesting that intermittent renal hilum occlusion may be an effective means of reducing surgical ischemic kidney injury in patients with renal tumor and diabetes in NSS.