雷帕霉素通过PI3K/AKT通路改善碘克沙醇致糖尿病大鼠肾损伤

目的观察雷帕霉素对碘克沙醇所致糖尿病大鼠肾损伤的保护作用,探讨其作用机制,为临床药物防治造影剂肾损伤提供理论依据。方法糖尿病大鼠45只,随机分为造影剂组(CM组,n=15)、雷帕霉素组(Rapa组,n=15)与空白对照组(NS组,n=15),SD大鼠被腹腔注射链脲佐菌素(STZ)建立糖尿病模型,随后给予碘克沙醇制备CIAKI模型,Rapa组给予雷帕霉素进行治疗,分别观察各组大鼠血中肌酐(Scr)、血尿素氮(BUN)的浓度变化;HE染色观察肾脏病理学变化;TUNEL检测肾上皮细胞凋亡情况、Western blot检测Bcl-2、Bax、PI3K、AKT、p-AKT表达情况。结果CM组大鼠肾功能损伤严重,小管上皮细胞破坏,肾小管空泡变性,细胞脱落至小管腔,肾小管上皮细胞凋亡。雷帕霉素干预后,Rapa组肾功能明显改善,肾小管上皮细胞损伤较轻,肾组织中Bax蛋白的表达较CM组明显降低,Bcl-2、PI3K、AKT、p-AKT表达明显升高,细胞凋亡数减少。结论雷帕霉素改善碘克沙醇导致的糖尿病大鼠肾功能损伤,与下调Bax表达、上调Bcl-2、PI3K、AKT、p-AKT表达相关。

Rapamycin improves renal injury induced by ioxanol in diabetic rats via PI3K/AKT pathway

Objective To observe the protective effect of rapamycin on renal injury in diabetic rats induced by ioxanol,and to explore its mechanism to provide theoretical basis for clinical drug targeting therapy.Methods Forty-five diabetic rats were randomly averagely divided into:contrast agent group(CM),rapamycin group(Rapa group),and blank control group(NS group).SD rats were injected with streptozotocin(STZ)intraperitoneally to establish diabetic model,and then ioxanol was given to prepare CIAKI model.Rapa group was given Raleigh.The contents of serum creatinine(Scr)and blood urea nitrogen(BUN)were determined,the pathological changes of kidney were observed by HE staining;the apoptosis of renal epithelial cells was detected by TUNEL,and the expressions of Bcl-2,Bax,PI3 K,AKT and p-AKT were detected by Western blot.Results Renal function and tubular epithelial cells were severely damaged in CM group,with vacuolar degeneration of renal tubules,cell shedding to tubular lumen and apoptosis of renal tubular epithelial cells.After rapamycin intervention,renal function was significantly improved and tubular epithelial cells were less damaged,the expression level of Bax protein in renal tissue was decreased,but increased for Bcl-2,PI3 K,AKT and p-AKT expressions.Conclusion Rapamycin improved the renal function in diabetic rats induced by ioxanol which is related to down-regulation of Bax expression,up-regulation of Bcl-2,PI3 K,AKT,p-AKT expression,and inhibition of tubular epithelial cell apoptosis.