选择性5－HT2A受体拮抗剂沙格雷酯延缓大鼠移植动脉急性排斥反应后纤维化  

Relief on fibrosis past acute rejection of the rat allograft artery from the specific 5-HT2A receptor blocker, sarpogrelate

作　　者：王海灏[1] 李明[1] 吴敏[1] 张伟杰[1] 陈知水[1] 阳军[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所教育部/卫生部器官移植重点实验室,武汉430030 [2]华中科技大学同济医学院附属同济医院血管外科,武汉430030

出　　处：《中华器官移植杂志》2011年第9期562-565,共4页Chinese Journal of Organ Transplantation

摘　　要：目的研究选择性5～羟色胺2A（5－HT2A）受体拮抗剂沙格雷酯延缓大鼠移植动脉急性排斥反应后纤维化的作用。方法实验分为3组，同种移植对照组（供、受者分别为Wistar大鼠和SD大鼠）、同系移植对照组（供、受者均为SD大鼠）和实验组（供、受者分别为Wistar大鼠和SD大鼠），建立大鼠腹主动脉移植急性排斥反应后纤维化模型。术后各组大鼠喂养条件相同，仅实验组大鼠每天给予沙格雷酯灌胃，25mg／kg。术后第14天和第60天对移植动脉行病理组织学及免疫组织化学检测，观察移植动脉内膜增生情况以及增殖细胞核抗原（PCNA）和平滑肌肌动蛋白（α-SMA）的表达情况。结果所有移植手术均获成功。术后第14天时，同种移植对照组移植动脉出现典型的急性排斥反应改变。术后第60天，同种移植对照组、同系移植对照组和实验组内膜指数分别为（62．41±6．54）％、（0．94±0．33）％和（16．71±3．94）％，3组间内膜指数的两两比较，差异均有统计学意义（P〈0．05）；PCNA和ccSMA细胞阳性率分别为（0．99±0．54）Vo和（0．79±0．33）％、（22．43±3．40）％和（23．70±2．78）％及（7．37±4．61）％和（8．21±3．11）％，3组间PCNA阳性率的两两比较及α-SMA阳性率的两两比较，差异均有统计学意义（P〈0．05）。结论大鼠移植动脉急性排斥反应后可继发严重纤维化，沙格雷酯可显著延缓急性排斥反应后纤维化的发生、发展，其作用机制可能与下调PCNA和α-SMA的表达有关。Objective To investigate the effect of sarpogrelate, a specific 5-HT2A receptor blocker, on fibrosis past acute rejection of abdominal aortic allotransplantation in rats. Methods The rat models of abdominal aortic transplantation were divided into three groups： allograft control group （Wistar→ SD）, isograft control group （SD→ SD） and sarpogrelate-treated group （Wistar→SD）. Sarpogrelate-treated group received intragastric administration of sarpogrelate every day. The pathologic and immunohistochemical findings of the transplant aorta were observed at 14th and 60th day after transplantation. Results At 14th day, visible acute rejection could be observed in allograft control group,but not in isograft control group. At 60th day, vascular intimal index of sarpogrelate- treated group was significantly lower than that in allograft control group [（ 16. 71 ± 3.94）% versus （62. 41 ± 6. 54） % ,P〈0. 05）. The expression of PCNA and α-SMA in sarpogrelate-treated group was also significantly lower than that in allograft control group [（7.37 ± 4.61）% versus （22.43 ± 3.40）%,（8.21 ± 3. 11）% versus. （23.70 ± 2.78）%,P〈0.05, respectively）. Conclusion The expression of PCNA and α-SMA of the transplant aorta could be suppressed by sarpogrelate, and sarpogrelate could relieve the fibrosis past acute rejection of aortic allograft.

关 键 词：大鼠 动脉 移植物 纤维化 沙格雷酯 

分 类 号：R363[医药卫生—病理学]