5-6肾切除大鼠早期模型中p38MAPK动态变化.doc

5/6肾切除大鼠早期模型中p38MAPK动态变化 　【摘要】 目的:研究5/6肾切除大鼠模型中p38MAPK磷酸化的动态表达情况。方法:82只雄性SD大鼠分为两组：5/6肾切除模型组72只，假手术对照组10只。模型组造模完成后，分别于肾切除早期（术后1/2 h、1 h、3 h、6 h、12 h、1 d、2 d、4 d）相应时间点处死，每组9只，假手术组于术后12 h处死，称量各组体重及残余肾重，计算肥大指数；下腔静脉取血留取血清测定血肌酐（Scr）、尿素氮（BUN）；以Western blotting免疫印迹法检测肾皮质磷酸化p38MAPK活性的表达情况；以病理光镜和电镜观察肾小球、肾小管及肾间质组织形态学及超微结构的变化。结果:模型组与对照组相比，肾脏呈代偿性肥大，肥大指数增高（Plt;0.05），Scr和BUN升高（P均lt;0.01）。免疫印迹法显示5/6肾切除术后1/2 h、1 h、3 h、6 h、12 h磷酸化p38信号呈递增趋势，尤以12 h信号最强，之后信号减弱，2 d时几乎不可见，4 d有较弱的信号，假手术组未见明显信号。光镜下，发现肾小球有轻度系膜细胞增生，基质增宽不明显，肾小管偶有轻度变性，间质偶有炎性细胞浸润。电镜下，偶见足突局灶融合。结论:5/6肾切除大鼠在造模完成后12 h时磷酸化p38MAPK表达最强。 【关键词】 5/6肾切除 p38MAPK 信号转导 磷酸化 Abstract: Objective:To investigate the dynamic expression of phosphorylating-p38 in the 5/6 subtotal nephrectomized (STNx) rat model. Methods:Eighty-two male Sprague-Dawley rats were randomly divided into two groups: STNx group(n=72) and sham group(n=10).Rats in STNx group were sacrificed in early nephrectomy at half of an hour, 1 hour, 3 hour, 6 hour, 12 hour, 1 day, 2 day and 4 day, 9 rats for each; rats of sham group were sacrificed at 12 hour. The body weight, kidney weight were measured and the kidney/body weight ratio was calculated in different groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined. The expressions of phosphorylating-p38 were measured with Western blotting in renal cortex. The histomorphology and ultrastructure of the renal glomerulus, tubule and interstitium were observed under light microscope and electron microscope. Results:The kidney were augmented for compensation in SNTx group and the kidney/body weight ratio in SNTx group was higher than that of the sham group, the same as the Scr and BUN(Plt;0.01).Western blotting displayed the signal of phosphorylating-p38 was increasing gradually from half of an hour to 12 hour after nephrectomy, especially the highest at 12 hour, then the signal weakened, signal almost disappear 2 days later and recorvered to tenuity signal 4 days later. Almost no expression of phosphorylating-p38