FoxO3a激活FasL介导肾缺血再灌注中肾小管上皮细胞凋亡的作用及机制  

Effect and its mechanism of FoxO3a activates FasL on renal tubular epithelial cell apoptosis induced by renal ischemia /reperfusion injury

作　　者：徐剑[1] 王艳[1] 姬怀雪[1] 胡书群[2] 董红艳[3] 任玲 

机构地区：[1]徐州医学院附属医院药剂科,江苏徐州221002 [2]徐州医学院生化教研室,江苏徐州221002 [3]徐州医学院神经生物研究中心,江苏徐州221002 [4]徐州市儿童医院药剂科,江苏徐州221002

出　　处：《中国临床药理学杂志》2014年第10期929-931,共3页The Chinese Journal of Clinical Pharmacology

基　　金：江苏省自然科学基金资助项目(BK2010171);徐州市科技局课题基金资助项目(XF11C099)

摘　　要：目的观察叉头框蛋白FoxO3a激活Fas配体FasL介导肾缺血再灌注损伤诱导肾小管上皮细胞凋亡的作用及机制。方法双侧夹闭大鼠肾蒂缺血45min后再灌注建立动物模型。免疫印迹分析FoxO3a、FasL的表达变化;原位缺口末端标记法检测大鼠肾小管上皮细胞凋亡情况;透射电镜观察肾小管上皮细胞凋亡的超微结构变化;生化全自动分析仪检测大鼠肾功能。结果大鼠肾缺血再灌注1 h后,FoxO3a及FasL蛋白表达水平明显增加;再灌注48 h,肾小管上皮细胞凋亡损伤加剧,凋亡数目明显增加,血肌酐及尿素氮水平明显升高,与假手术组相比,差异有统计学意义(P<0.05,P<0.01)。结论大鼠肾缺血再灌注能诱导FoxO3a激活,进而上调FasL的表达,促进肾小管上皮细胞凋亡,加剧肾组织损伤。Objective To explore the role and mechanism of forkhead box proteinO3a activates Fas ligand on renal tubular epithelial cell （ RTC ） apoptosis induced by renal ischemia /reperfusion （ I/R ） . Methods The model by clamping renal pedicles for 45 minutes follow-ing reperfusion was established.The protein expression of forkhead box proteinO3a and Fas ligand were examined by western blotting.Apoptosis of RTC was assessed by TdT -mediated dUTP nick -end Labeling （TUNEL） method and transmission electron microscopic （TEM）.Renal function was assessed by biochemical automatic analyzer .Results The protein expression level of forkhead box proteinO 3a and Fas ligand was increased significantly following renal I /R at 1 h.RTC nucleus was shrinking, crushing followed renal I /R, and a significant increase in the number of TUNEL -positive cells following renal I /R was displayed com-pared with the sham group.The level of blood urea nitrogen（BUN） and serum creatinine （ Scr） was increased significantly compared with the sham group （P 〈0.05,P 〈0.01）.Conclusion FoxO3a could be acti-vated during renal I /R, and then up -regulated FasL protein expression , facilitated renal tubular epithelial cell apoptosis , in turn, aggravated renal I /R injury in rats.

关 键 词：叉头框蛋白 FAS 配体 缺血再灌注 肾小管上皮细胞 凋亡 

分 类 号：R963[医药卫生—微生物与生化药学]