雄激素受体拮抗剂氟他胺在大鼠同种肾移植慢性排斥反应中的作用  

Effects of androgen antagonist flutamide on chronic rejection of renal homotransplantations in rat

作　　者：姚友生[1] 黄海[1] 黄健[1] 蔡奕川[1] 王家伟[1] 王涛[1] 

机构地区：[1]中山大学附属第二医院泌尿外科,广州510120

出　　处：《中华实验外科杂志》2008年第2期242-244,共3页Chinese Journal of Experimental Surgery

基　　金：广东省自然科学基金资助项目（04009393）

摘　　要：目的探讨雄激素受体拮抗剂氟他胺对移植肾慢性排斥反应的影响。方法以雄性Lewis大鼠作受者，以雌、雄Fisher大鼠作供者，建立大鼠同种肾移植慢性排斥反应动物模型。用雄激素受体拮抗剂氟他胺按25mg／kg体重喂食试验组20周，移植后每4周检测受者的24h尿蛋白、血肌酐、肌酐清除率；移植后20周处死受者大鼠，对移植肾进行显微镜检、免疫组织化学、核糖核酸酶保护测定等检测，对比试验组与对照组数据评价氟他胺对移植肾的影响。结果两组比较，不论雄性供者还是雌性供者的大鼠的24h尿蛋白、肌酐清除率具有明显的差异，试验组的肾功能受损较轻。两组移植肾组织血管内膜增厚、肾小球硬化和间质纤维化程度以及单核巨噬细胞细胞浸润，转化生长因子（TGF）-β和白细胞介素（IL）-6的mRNA表达程度差异均有统计学意义，试验组组均低于对照组（P〈0．05）。结论在大鼠同种肾移植慢性排斥动物模型上，雄激素受体拮抗剂氟他胺可以明显抑制慢性排斥的发生。Objective To research the effects of androgen antagonist flutamide on chronic rejection of renal transplantation. Methods Male Lewis rats were used as recipients, and male or female Fisher rats as donors. After the establishment of chronic rejection model following renal transplantation ,half of the rats were treated with flutaminde （25 mg/kg body weight） every day, and the rest were treated without any medicine. In all rats ,24-h urine protein, serum creatinine and creatinine clearance rate were tested every 4 weeks, and after 24 weeks, all the rats were executed, and the renal grafts were observed under microscopy and subjected to immunohistology and RNase protection assay. The data of the two groups were compared and the effects of flutamide on the chronic rejection were evaluated. Results There was obviously difference in 24-h urine protein and creatinine clearance rate between the two groups, and the function of the renal grafts was more severely injured in the control group. The thickening of endangium, glomerular sclerosis, interstitial fibrosis and lymphocyte infiltration had statistical difference between the experimental group and contol group. The mRNA expression levels of TGF-β and IL-6 in experimental group were lower than in control group. Conclusion The flutaminde could significantly inhibit the occurrence of in the rat model of chronic rejection following allograft transplantation.

关 键 词：肾移植 雄激素 慢性排斥反应 模型 动物 

分 类 号：R699.2[医药卫生—泌尿科学]