免疫抑制剂对慢性移植物肾病大鼠移植肾C4d沉积的影响  

Influence of immunosuppressants on C4d deposition in renal allografts of rats with chronic allograft nephropathy

作　　者：杨立[1,2] 李涛[1,2] 卢一平[3] 罗光恒[4] 宋珺 王志平[1,2] 

机构地区：[1]兰州大学第二医院泌尿外科 [2]兰州大学泌尿外科研究所,甘肃省泌尿系统疾病临床医学中心,甘肃省泌尿系统疾病研究重点实验室,兰州730030 [3]四川大学华西医院泌尿外科,成都610041 [4]贵州省人民医院泌尿外科,贵州550002 [5]三亚市人民医院泌尿外科,海南572000

出　　处：《第二军医大学学报》2013年第5期477-481,共5页Academic Journal of Second Military Medical University

摘　　要：目的观察慢性移植物肾病(CAN)大鼠模型移植肾中C4d的沉积情况,并分析免疫抑制剂对C4d沉积的影响。方法将Fisher 344大鼠的肾移植到Lewis大鼠体内复制CAN模型,术后给予环孢素A(CsA)10 mg/(kg·d)×10 d。将模型鼠随机分为5组,每组9只,分别给予不同的药物:(1)生理盐水对照组;(2)CsA[6 mg/(kg·d)]组;(3)雷帕霉素[RAPA,0.8 mg/(kg·d)]组;(4)他克莫司[FK506,0.15 mg/(kg·d)]组;(5)霉酚酸[MMF,20 mg/(kg·d)]组。分别在术后第4、8及1 2周时处死每组大鼠3只,留取移植肾标本,根据Banff 97标准评价组织病理改变,用免疫荧光法检测C4d沉积情况。结果移植后第4周,各移植组中均未发现明显的CAN临床病理改变,各组Banff标准评分差异无统计学意义(P>0.05),但各组受体大鼠移植肾肾小管周围毛细血管(PTC)部位均出现C4d阳性沉积;术后8周各组均不同程度出现CAN的典型病理变化,PTC部位的C4d沉积增强;术后12周时CAN进展到最严重阶段,PTC部位的C4d沉积程度达到最大。C4d沉积与移植肾CAN病理改变呈正相关(r=0.894,P=0.000)。同对照组相比,CsA组和FK506组C4d沉积程度差异均无统计学意义(P>0.05),而MMF组和RAPA组能够减少C4d的沉积,差异有统计学意义(P<0.05)。结论大鼠肾移植后,PTC部位可出现C4d沉积,且产生的时间早于CAN发展的病理变化,同时C4d沉积的表达与CAN的进展相关。MMF和RAPA能够抑制CAN的进展,CsA和FK506无明显抑制作用。Objective To observe C4d deposition in renal allografts of rats undergoing chronic allograft nephropathy （CAN）, and to analyze the effects of immunosuppressants on deposition of C4d in peritubular capillaries. Methods The renal grafts of Fisher 344 rats were orthotopically transplanted into Lewis rats to create CAN models, and all the recipients were given cyclosporine A （CsA） 10 mg/（kg ·d） X 10 d after operation. The models were then divided into 5 groups （each n=9）： Group A was normal saline control group, only receiving vehicle orally; Group B, G, D, and E received CsA 6 mg/（kg· d）, RAPA 0.8 mg/（kg ·d）, FK506 0. 15 mg/（kg · d）, and MMF 20 mg/（kg ·d）, respectively. The renal allografts were harvested after three rats were sacrificed at the 4^th , 8^th and 12^th weeks post-transplantation. The histological changes were assessed according to Banff 97 standard. The deposition of C4d was detected by immunofluorescenee method. Results C4d deposition in peritubular capillary（PTC） was found in all the allografts at the 4^th week after transplantation, while there were noobvious clinical pathological changes of CAN in all groups, and the Banff scores were not significantly different among different groups （P〉0. 05）. CAN manifestations of different degrees were observed 8 weeks after operation, with increased C4d deposition in the PTC. Severest CAN was observed at the 12^th week after operation, accompanied by the most C4d deposition in the PTC. C4d deposition was positively correlated with the severity of CAN （r=0. 894, P 0. 000）. Compared with the control group, CsA and FK506 showed no significant effect on C4d deposition （P〉0.05） ; however, MMF and RAPA significantly decreased C4d deposition （P~ 0. 05）. Conclusion Deposition of C4d in PTC may appear in allografts earlier than the pathological changes of CAN, and the deposition is associated with the progression of CAN. MMF and RAPA can inhibit the progression of CAN, while CsA and FK506 can not.

关 键 词：慢性移植物肾病 抗体生成 C4D 免疫抑制剂 

分 类 号：R692[医药卫生—泌尿科学]