西罗莫司抑制胆管缺血后代偿性增生的初步研究  

Rapamycin inhibits compensatory bile duct growth after ischemic injury

作　　者：吴田田[1] 杨广顺[1] 赵军[1] 杨宁[1] 张海斌[1] 钟鑫平[1] 邵卓[1] 

机构地区：[1]第二军医大学东方肝胆外科医院胆道二科,上海200438

出　　处：《第二军医大学学报》2008年第7期800-803,共4页Academic Journal of Second Military Medical University

摘　　要：目的:探讨雷帕霉素对大鼠肝内胆管缺血后代偿性增生的影响。方法:雄性SD大鼠随机分配到对照组(假手术组,n=28),假手术+雷帕霉素组(n=28),缺血组(n=32),缺血+雷帕霉素组(n=32),缺血组完全离断肝脏动脉血供,雷帕霉素处理组每日予雷帕霉素2.0mg/kg灌胃,术后1、3、7、14d处死动物,取肝组织行H-E、Ki-67染色,高倍镜视野下计数汇管区内小叶间胆管,汇管区周围小胆管,Ki-67阳性及阴性胆管细胞,计算平均小叶间胆管及汇管区周围胆管数目(总计数胆管数目/总汇管区数目),Ki-67(+)胆管细胞/Ki-67(-)胆管细胞比值。结果:与对照组比较,缺血组术后平均小叶间胆管数量明显增加,给予雷帕霉素后,胆管缺血大鼠术后7、14d平均小叶间胆管数目减少;术后3d,缺血组Ki-67阳性与阴性胆管细胞比值达到高峰1.59±0.17,明显高于对照组,给予雷帕霉素后,峰值水平降低。结论:雷帕霉素影响缺血胆管上皮细胞Ki-67抗原表达,抑制肝内胆管代偿性增生。Objective： To explore the impact of rapamycin on compensatory bile duct growth in response to ischemic injury. Methods： Male SD rats were randomly assigned to 4 groups： sham （n = 28）, sham＋ rapamycin （ rapa, n = 28 ）, ischemia （n = 32）, ischemia＋rapa group （n = 32）. Complete hepatic arterial deprivation was performed in the latter 2 groups; gastric lavage with rapamycin （2 mg/kg/day ） was given to rats in rapa groups. Fresh liver tissues were obtained on day 1,3,7, and 14 postoperatively and were subjected to immunohistochemical staining （H-E, Ki-67）. Interlobular bile duct within portal tract and periportal bile ductuli were counted in H-E stained sections. Ki-67 positive and negative bile duct epithelial cells were counted in Ki-67 immunolabelled sections. Average interlobular ducts,periportal duculi and ratio of Ki-67 positive epithelial cells/negative epithelial cells were calculated. Results： Ischemia group had obviously increased number of interlobular ducts compared to sham group. Rapamycin lavage inhibited interlobular duct increase on day 7 and day 14 postoperatively compared with ischemia group. In ischemia group Ki-67（ ＋ ）/（-） ratio reached its peak level （1.59±0.17） 3 days after operation, being significantly higher than that of sham group. Rapamycin decreased the peak value of Ki-67（＋）/（- ） ratio. Conclusion ： Rapamycin can reduce expression of Ki-67 antigen and inhibit compensatory bile duct proliferation in response to ischemic injury.

关 键 词：西罗莫司 胆管 缺血 增生 KI-67抗原 

分 类 号：R657.3[医药卫生—外科学]