晚期糖基化终末产物受体-核因子-κB信号通路在大鼠肾脏缺血再灌注损伤中的作用  

Role of receptor for advanced glycation end - products nuclear factor - κB signaling regulating pathway in renal ischemia reperfusion injury in rats

作　　者：王玉浔[1,2] 安雅臣 蒋艳茹 姜埃利[1] 

机构地区：[1]天津医科大学第二医院泌尿外科血液净化中心,300201 [2]华北理工大学附属医院肾内科,唐山063007 [3]华北理工大学附属医院神经内科,唐山063007 [4]唐山市中医医院肾内科,063007

出　　处：《中华实验外科杂志》2017年第9期1529-1531,共3页Chinese Journal of Experimental Surgery

摘　　要：目的 探讨晚期糖基化终末产物受体-核因子-κB（RAGE-NF-κB）信号通路在大鼠肾脏缺血再灌注损伤中的作用，以及抗氧化剂α硫辛酸（ALA）的保护作用。 方法 采用无创动脉夹夹闭双侧肾蒂制作急性缺血再灌注肾损伤大鼠模型。将SD大鼠随机分成3组：假手术组（腹腔注射60 mg/kg生理盐水，Sham S组）、模型组（IR组）、ALA预处理组（ALA 60 mg/kg于缺血再灌注前30 min腹腔注射，ALA组）。麻醉后分别于再灌注后1、6、12 h后处死大鼠，苏木素-伊红（HE）染色观察肾组织病理变化；采用苦味酸法测定血清肌酐；酶联免疫吸附法（ELISA）检测血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平；Western blot检测肾组织中RAGE及NF-κB蛋白的表达水平；反转录-聚合酶链反应（RT-PCR）法检测肾组织RAGE mRNA及NF-κB mRNA的表达水平。结果 3组血肌酐水平总体存在差异，IR组及ALA组的血肌酐水平均较S组升高，差异有统计学意义（F＝4.867，P＝0.013），ALA组升高幅度降低，与IR组比较差异有统计学意义（F＝5.412，P＝0.010）；3组TNF-α、IL-6总体水平差异有统计学意义（F＝12.881，P＝0.001），IR组明显升高，ALA组明显下降；3组RAGE mRNA、NF-κB蛋白及mRNA表达水平总体差异有统计学意义，IR组明显升高，ALA组明显下降。结论 RAGE-NF-κB信号通路可能参与了缺血再灌注所致的急性肾损伤，抗氧化剂α-硫辛酸对缺血再灌注急性肾损伤具有保护作用。Experimental Study Role of receptor for advanced glycation end-products nuclear factor-κB signaling regulating pathway in renal ischemia reperfusion injury in rats Objective To investigate the role of receptor for advanced glycation end-products nuclear factor-κB （RAGE-NF-κB） signaling pathway in the renal ischemia reperfusion injury in rats. Methods The rats of acute ischemia reperfusion injury （RIRI） model was induced by bilateral clamping the renal artery and vein for 45 minutes followed by reperfusion. Fifty-four SD rats were divided into 3 groups by complete randomization method （18 cases in each group）. （1） Sham surgery group （Intraperitoneal injection of 60 mg/kg saline solution, S-group）; （2） Model group; （IR） （3） Alpha lipoic acid pretreatment group （ALA 60 mg/kg intraperitoneal injection of 30 min before reperfusion ALA-group）. Observed the general situation in rats, animals were killed in different reperfusion time （1, 6, 12 h）. Renal patho-histological changes were examined by hematoxylin and eosin （HE） staining; The level of blood urea nitrogen was measured by Jaffe’s assay; The expression of interleukin （IL）-6 and tumor necrosis factor-α （TNF-α） were measured by enzyme linked immunosorbent assay （ELISA）; RAGE protein and NF-κB protein were determin-ed by Western blotting; The expression of renal RAGE mRNA, NF-κB mRNA were detected by real-time quantitative polymerase chain reaction （Real-time PCR）.Results As compared with the sham operation group, the blood levels of Scr in IR group were significantly elevated （F=4.867, P=0.013）; the expression of renal RAGE protein and RAGE mRNA, NF-κB protein RAGE mRNA in IR rats were increased significantly. Compared with IR group, the expression of Scr, TNF-α, IL-6, RAGE protein and RAGE mRNA, NF-κB protein RAGEs mRNA in ALA group rats were decreased significantly. Conclusion RAGE-NF-κB signaling pathway regulates the enal ischemia reperfusio-ninjury rats. ALA has a protective eff

关 键 词：缺血再灌注损伤 晚期糖基化终末产物受体 核因子-ΚB 肾脏 大鼠 Α-硫辛酸 

分 类 号：R692[医药卫生—泌尿科学]