诱导型一氧化氮合酶抑制剂防治大鼠腹主动脉移植术后慢性排斥反应  

Effects of a novel inhibitor of nitric oxide synthase on chronic arterial allograft rejection in rats

作　　者：欧阳骏[1] 温端改[1] 严春寅[1] 侯健全[1] 徐大生[2] 齐世杰[2] 马安伦[2] 蒋文雷[2] 陈惠方[2] 

机构地区：[1]苏州大学附属第一医院泌尿外科,215006 [2]加拿大蒙特利尔大学Notre-Dame医院器官移植中心

出　　处：《中华器官移植杂志》2005年第10期619-621,共3页Chinese Journal of Organ Transplantation

基　　金：苏州市2003年国际科技合作基金资助项目

摘　　要：目的研究移植物慢性排斥反应血管变化的机制,评价新型诱导型一氧化氮合酶(iNOS)抑制剂(FR260330)防治大鼠腹主动脉移植术后慢性排斥反应的作用。方法供者为ACI大鼠,受者为Lewis大鼠。采用原位腹主动脉移植,移植后2周和12周时分别处死受者,取其移植腹主动脉,用光学显微镜及计算机图像分析系统分析腹主动脉内膜、平滑肌及外膜的面积及内膜/内膜+中层比例。并以α肌动蛋白(αactin)免疫组织化学法进行内膜、中层细胞成份分析。术后分别单独或联合应用FR260330和他克莫司(FK506)抗排斥反应。结果移植后用iNOS抑制剂组3个月时血管内膜/内膜+中层比例明显小于不用药对照组;移植后不用药对照组及用FK506组的血管中层细胞均出现不同程度破坏;用iNOS抑制剂组的血管内膜比用FK506组更光滑,破坏情况也较少。结论iNOS抑制剂对慢性排斥反应有抑制作用。Objective To evaluate the effects of a novel inducible nitric oxide synthase （iNOS） inhibitor （FR260330） in prevention of chronic rejection in a model of rat aortic allograft and to investigate the mechanism of the arterial wall lesion of chronically rejecting solid organ grafts. Methods Male Lewis （LEW, RT1^l） rats received male ACI （RT1^a） aorta allografts or LEW aorta isografts. Seven groups （n≥12） were involved in this study. FR260330 and/or tacrolimus were administered orally for 14 or 90 days according to protocol. The degree of intimal proliferation of graft aorta was determined by a computerized image system. Results Both low and high doses of FR260330 or tacrolimus treated grafts showed significantly decreased intima/（intima ＋ media） ratios at day 90 compared with placebo controls. Combined therapy of low-dose of FR260330 with low-dose of tacrolimus produced a significant decrease of intima/（intima ＋ media） ratios with intact endothelium as compared with placebo controls. Anti-a-actin immunohistochemical staining demonstrated that one of the mecha- nisms of intimal proliferation was related to migration of vascular smooth muscle cells. The intima in iNOS inhibition groups was more smooth than in placebo control group and low-dose FK506 treated groups. Conclusions A selective inhibitor of nitric oxide synthase, FR260330 plays a protective role in chronic aortic allograft rejection in the rat. Combined therapy of low-dose of FR260330 with tacrolimus produces significant protection of immune injury and may serve to improve long-term graft survival and function.

关 键 词：一氧化氮合酶 大鼠 腹腔动脉 移植 移植物排斥 诱导型一氧化氮合酶抑制剂 慢性排斥反应 鼠腹主动脉 移植术后 诱导型一氧化氮合酶(iNOS) 

分 类 号：R654.3[医药卫生—外科学]