反义基因治疗对慢性增生性胆管炎的抗增殖作用  

Efficacy of antisense gene therapy for proliferative cholangitis

作　　者：周涌[1] 李富宇[1] 王晓东[1,2] 蒋力生[1] 程南生[1] 李全生[1] 何生[1] 

机构地区：[1]四川大学华西医院肝胆外科,四川省成都市610041 [2]佳木斯市中心医院,黑龙江省佳木斯市154002

出　　处：《世界华人消化杂志》2010年第8期767-772,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30801111;教育部博士点新教师基金资助项目;No.200806101065~~

摘　　要：目的:探讨并对比PCNA、c-Myc、cdc2k shRNA对PC的过度增殖和成石潜力的影响,以期筛选PC抗增殖治疗的最佳靶点.方法:经十二指肠乳头向胆总管内逆行插入尼龙缝合线建立慢性增生性胆管炎的大鼠实验模型.三种反义治疗组则以尼龙缝合为导引向胆总管内分别注入0.5mL的PCNA、c-Myc或cdc2k shRNA.结果:PCNAshRNA治疗组的胆道黏膜上皮和胆管壁胶原纤维的过度增殖程度均明显低于c-Myc、cdc2k shRNA治疗组;此外,PCNA shRNA治疗组胆管壁的黏蛋白基因表达及黏蛋白分泌也低于c-Myc、cdc2k shRNA治疗组.结论:PCNA shRNA治疗能够更为有效的抑制PC病变胆管的胶原纤维过度增生及黏液过度分泌,更有望达到预防胆道再狭窄和结石术后复发的目的.AIM：To compare the effects of short hairpin RNAs （shRNAs） targeting the proliferating cell nuclear antigen （PCNA）,c-Myc and cdc2 k genes on the hyperplastic behavior and lithogenic potential of proliferative cholangitis （PC）,and to select the best target for antiproliferative treatment of PC.METHODS：A rat model of PC was developed by retrogradely inserting a nylon thread into the common bile duct.Using the nylon thread as the guide wire,an intralumenal injection of PCNA,c-Myc and cdc2 k shRNAs into the common bile duct was performed in three different groups of model rats,respectively.RESULTS：Compared to the c-Myc and cdc2 k shRNA treatment groups,the degree of hyperplasia of biliary epithelium and collagen fibers in the bile duct wall in the PCNA shRNA treatment group were significantly decreased.In addition,the protein expression and secretion of mucin from the hyperplastic biliary epithelium and peribiliary gland were remarkably reduced in the PCNA shRNA treatment group.CONCLUSION：PCNA shRNA possesses more strong inhibitory effects on collagen fiber hyperplasia in and mucin secretion from the bile duct wall of rats with experimental PC than c-Myc and cdc2 k shRNAs.Therefore,PCNA shRNA holds more promise for prevention of postoperative biliary restenosis and stone recurrence in PC patients.

关 键 词：肝内胆管结石 慢性增生性胆管炎 复发 胆道狭窄 反义基因治疗 

分 类 号：R657.4[医药卫生—外科学]