磷酸化糖原合成酶激酶-3β在大鼠移植肾早期病理改变中的作用  

Role of glucogen synthase kinase-3β in a rat kidney model of chronic allograft nephropathy

作　　者：王玉新[1] 张以勤[1] 李怀富[2] 叶婧[1] 邹和群[3] 史艳玲[4] 陈玲[2] 周文英[2] 

机构地区：[1]厦门市第二医院肾内科,福建省厦门市361021 [2]中山大学附属第五医院 [3]南方医科大学附属第三医院 [4]温州医学院附属第一医院

出　　处：《中华器官移植杂志》2011年第11期683-687,共5页Chinese Journal of Organ Transplantation

摘　　要：目的探讨糖原合成酶激酶-3β（GSK-3β）在大鼠移植肾早期病理改变中的作用。方法以F344大鼠为供者，Lewis大鼠为受者，依照标准的慢性移植肾。肾病（CAN）模型要求行左肾原位移植，制作CAN模型（移植组）。术后7d切除受者的右肾。以切除一侧。肾脏的雄性F344大鼠和Lewis大鼠为对照（F344对照组和LEW对照组）。分别于术后4、8、12、16及24周时收集24h尿液，采集血液，测定24h尿蛋白和血肌酐，取移植肾组织，观察组织学改变，并用免疫组化法检测肾组织中磷酸化GSK-3β表达。结果移植组术后早期（4、8和12周）移植肾病理改变主要表现为单个核细胞浸润、血管平滑肌细胞（SMC）的移行增殖，在后期（16和24周）尿蛋白排泄率显著增高，移植肾病理改变表现为肾间质单个核细胞浸润明显增加及严重的肾间质纤维化、肾小管萎缩。移植组术后各时间点移植肾组织中磷酸化GSK-3β及其mRNA表达水平均显著低于LEW对照组和F344对照组相同时点的表达水平（P〈0．05），并随着移植时间的延长进一步降低。磷酸化GSK-3β表达水平与早期肾间质单个核细胞浸润程度、SMC移行增殖及后期肾间质纤维化、肾小管萎缩、血管硬化程度呈显著负相关。结论磷酸化GSK-3β表达下调在大鼠移植。肾早期的肾间质单个核细胞浸润、SMC移行增殖及后期的肾间质纤维化、肾小管萎缩、肾血管硬化病变的发生中均起重要作用。Objective To investigate the expression and significance of glucogen synthase kinase-3β （GSK-3β） in the pathogenesis of chronic allograft nephropathy （CAN） in rats. Methods Kidneys of Fisher （F344） rats as donors were orthotopically transplanted into Lewis fLEW） rats as recipients. The renal function and histopathological changes were observed at 4, 8, 12, 16, and 24 week post-transplantation. Phosphorylated GSK-3β（p-GSK-3β） protein and mRNA expression was determined by using immunohistological assays and RT-PCR respectively. Results Our data showed that 24-h urinary protein excretion in CAN rats was increased significantly at week 16 as compared with F344/LEW controls. Allografts showed markedly increased mononuclear cells infiltration and presented with severe interstitial fibrosis and tubular atrophy at 16 and 24 week post-transplantation. p-GSK-3β expression （protein/mRNA） was down-regulated in rat kidneys with CAN, and the decrease became more significant over time after transplantation, p-GSK-3β expression was correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells migration in vascular wall, and interstitial fibrosis. Conclusion It was concluded that GSK-3β down-regulation was the key event that may be involved in mononuclear cells infiltration and vascular SMCs migration at early stage, and interstitial fibrosis and allograft nephroangiosclerosis at later stage of CAN pathogenesis in rats.

关 键 词：大鼠 肾移植 慢性移植肾肾病 糖原合成酶激酶3 

分 类 号：R363[医药卫生—病理学]