摘要
目的:观察泛素在慢性移植肾病(CAN)大鼠肾组织中的表达及其与肾功能改变、病理学改变及肾组织正常活化T细胞表达及分泌趋化因子(RANTES)之间的关系,探讨泛素在CAN中的作用。方法:实验组采用近交系大鼠的同种异基因动物间的左肾原位移植,雄性F344大鼠40只为供体,雄性LEW大鼠40只为受体,移植手术后第10d行右肾切除术,对照组采用单肾切除术的雄性F344和LEW大鼠各25只。分别于4周、8周、12周、16周及24周处死大鼠,做肾功能、移植肾组织学检测,并应用免疫组织化学与免疫印迹方法检测肾组织中泛素的表达,应用免疫组织化学方法检测肾组织RANTES的表达。结果:移植组大鼠尿蛋白定量、血清肌酐水平于移植后16周时显著增高,24周时更为显著。肾脏病理显示:移植后12周之前,主要表现为肾间质单个核细胞浸润,血管平滑肌细胞增殖及血管内膜的断裂;移植后16周时可观察到肾小球硬化、肾间质纤维化及血管硬化等慢性病理改变。免疫组织化学及Western-blot结果显示泛素在CAN病程中的表达呈逐渐升高后又降低的过程,移植12周为其表达高峰,后逐渐降低,24周时降至最低。免疫组织化学结果显示RANTES表达部位,表达时相与泛素表达是一致的。相关分析显示,肾移植大鼠泛素表达水平与24h尿蛋白定量、血清肌酐水平在CAN早期呈正相关,在CAN晚期呈负相关。与肾间质纤维化程度呈负相关。移植12周组泛素表达水平与RANTES呈显著正相关。结论:泛素在CAN早晚期病变中起连接作用,泛素对上调增殖起基本作用,并可能通过对RANTES的调节,参与了CAN的全过程。
Objective：To investigate the renal expression and role of ubiquitin on the chronic allograft nephropathy （CAN） model. Methods： The kidney of Fisher（F344）rats were orthotopically transplanted into Lewis recipients. Animals were harvested respectively at 4 weeks, 8weeks, 12weeks, 16weeks, 24weeks after transplantation for renal ruction and histologycal examination. The expression of ubiqutin was determinated with Western- blot and immunohlstolehemistry assay, while expression of RANTES was determined by immunohistochemistry. Results： The expression of both ubiquitin and RANTES in allograft increased at weekl2, then declined, The peak of increased was at 12 week after transplantation. The expression of ubiquitin and RANTES were correlated with 24 - hour urine protein extent,serum ereatinine levels in early- stage of CAN, while negative- correlation in advanced -stege of CAN. There was a significant positive correlation between RANTES and ubiquitin in CAN rats at 12 weeks after transplantation. Conclusion： Ubiquitin might play a role in mediating the convention of the early and late phase of CAN., ubiquitin play a fundamental role in the upregulating proliferation . Ubiquitin were also involved in the total course of CAN via regulating RANTES.
出处
《中国中西医结合肾病杂志》
2006年第4期208-211,共4页
Chinese Journal of Integrated Traditional and Western Nephrology
基金
珠海市科技局基金资助项目(No.PC20052035)
关键词
慢性移植肾病
泛素
RANTES
Chronic allograft nephropathy Ubiqutin Regulated upon activiation normal T cell expressed （RANTES）
