肾移植急性排斥反应中Fas-L表达与肾小管上皮细胞凋亡的研究  

Study on the expression of Fas-Ligand and apoptosis of tubular epithelial cells during renal allograft rejection

作　　者：史其新[1] 高翔[2] 谢蜀生[2] 郭应禄[1] 

机构地区：[1]北京大学第一医院泌尿外科,100034 [2]北京大学免疫系

出　　处：《中华实验外科杂志》2000年第6期543-545,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金!重点资助项目 (39830 340 )

摘　　要：目的　探讨异基因大鼠肾移植急性排斥期肾小管上皮细胞凋亡与Fas L表达的变化。方法　选用近交系DA(RT1a)、LEW (RT11)大鼠进行原位左肾移植。实验组 :异基因移植组 (DA→LEW ) ;对照组 :同基因移植组 (LEW→LEW )。于手术后第 2、4、6天分别取移植肾进行病理学检查及电镜扫描 ,采用末端脱氧核苷酸转移酶 (TdT)介导的脱氧核苷酸原位末端标记法 (TUNEL)检测移植肾脏中的凋亡细胞 ,逆转录 (RT1a)聚合酶链反应 (RT PCR)方法检测供肾及受体脾中Fas L表达的变化。结果　病理学检查结果显示实验组大鼠在术后第 2、4、6天分别发生轻、中、重度排斥 ,对照组无明显排斥现象。TUNEL法结果显示实验组于手术后第 2、4、6天细胞凋亡数均明显高于对照组 (P <0 .0 1) ,手术后第 4天差异最大 ,手术后第 6天因严重排斥而使肾小管上皮细胞坏死脱落 ;RT PCR结果显示 ,Fas L在异基因肾移植排斥组供肾中表达增高。供肾中Fas L表达及肾小管上皮细胞凋亡程度与病理学检查结果一致。结论　Fas/Fas L介导的肾小管上皮细胞凋亡在大鼠异基因肾脏移植急性排斥反应中发挥重要作用 ,脾脏可通过Fas/Fas L介导的“活化诱导的细胞死亡 (AICD)”清除完成排斥反应表达Fas L的淋巴细胞。Objective\ To explore the changes of apoptosis of tubular epithelial cells and expression of Fas Ligand (Fas L) during renal allograft rejection in rats. Methods\ Orthotopic left kidney transplantation was performed on inbred rat DA (RT1 a) and inbred rat LEW (RT1 1). Experimental group: allogenic transplant group (DA→LEW), control group: (LEW→-LEW). The grafts were harvested on day 2, 4, 6 after operation. All graft samples were subjected to histological examination and electron microscopic examination. Apoptosis cells of grafts were monitored by terminal deoxynucleotidy transferase mediated dUTP nick end labeling (TUNEL) method, and the Fas L level detected by using reverse transcription chain reaction (RT PCR) in the renal allografts and spleens of recipients. Results\ Histologically, mild, moderate and severe acute rejection occurred on day 2, 4, 6 after operation in the experimental group respectively. But none of control group had the histological evidence of acute rejection. The TUNEL showed that the number of apoptosis cells in the experimental group were significantly higher than in the control group on the day 2, 4, 6 ( P <0.01). The variance was the most obvious on day 4 after operation. Necrosis or exfoliation of the tubular epithelial cells partly occurred due to severe rejection on the day 6 after operation. Fas L expression in renal allografts was increased. The expression of Fas L and the apoptotic degrees of tubular epithelial cells were in correspondant with the degree of histological damage. Conclusion\ The Fas/Fas L mediated apoptosis of tubular epithelial cells might play an important role in acute rejection of renal allograft in rats. The spleen might eliminate the lymphocytes expressing Fas L after completion of the acute rejection by “activated induced cell death” mediated by Fas/Fas L.\;

关 键 词：肾移植 FAS-L 急性排斥反应 细胞凋亡 

分 类 号：R699[医药卫生—泌尿科学]