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西罗莫司抑制胆管缺血后代偿性增生的初步研究
吴田田,杨广顺,赵军*,杨宁,张海斌,钟鑫平,邵卓
0
(第二军医大学东方肝胆外科医院胆道二科,上海 200438)
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2.0 mg/kg灌胃,术后1、3、7、14 d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、14 d平均小叶间胆管数目减少;术后3 d,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。
关键词:  西罗莫司  胆管  缺血  增生  Ki-67抗原
DOI:10.3724/SP.J.1008.2008.00800
投稿时间:2007-11-28修订日期:2008-04-25
基金项目:
Rapamycin inhibits compensatory bile duct growth after ischemic injury
WU Tian-tian,YANG Guang-shun,ZHAO Jun*,YANG Ning,ZHANG Hai-bin,ZHONG Xin-ping,SHAO Zhuo
(Second Department of Biliary Surgery,Eastern Hepatobiliary Hospital,Second Military Medical University,Shanghai 200438,China)
Abstract:
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.
Key words:  sirolimus  bile ducts  ischemia  hyperplasia  Ki-67 antigen