塞来昔布在胆管炎中的抗增殖作用  

Anti-proliferation activity of celecoxib in cholangitis

作　　者：陈文龙[1] 蒋力生[1] 李富宇[1] 

机构地区：[1]四川大学华西医院胆道外科,四川省成都市610041

出　　处：《世界华人消化杂志》2010年第17期1761-1766,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30801111~~

摘　　要：目的:探讨塞来昔布在慢性增生性胆管炎(chronic proliferative cholangitis,CPC)治疗中的应用价值.方法:健康♂SD大鼠30只,随机分为3组:假手术组(n=10),CPC模型组(n=10),塞来昔布治疗组(n=10).模型组及治疗组经十二指肠乳头向胆总管逆行插入5-0尼龙缝合线,直至肝门.假手术组仅开腹后关腹.术后第1天开始治疗组予塞来昔布50mg/(kg·d)腹腔注射.1wk后处死动物.通过HE染色、Masson染色、PAS染色及免疫组织化学评估塞来昔布能否对CPC中过度增殖的胆管黏膜上皮、黏膜下腺体、胆管壁胶原纤维产生抑制作用及其效果.结果:塞来昔布治疗组胆管黏膜上皮、黏膜下腺体、胆管壁胶原纤维的增殖较CPC模型组受到明显的抑制,但略高于假手术组,免疫组织化学示环氧化酶2(cyclooxygenase2,COX-2)表达明显弱于CPC模型组(IA值:8.62±0.19vs35.27±0.43,P<0.05),与假手术组接近(IA值:8.62±0.19vs8.41±0.13,P>0.05).结论:塞来昔布可通过对COX-2的表达抑制,有效抑制胆管黏膜上皮、黏膜下腺体、管壁胶原纤维的过度增殖,降低黏蛋白的高分泌,从而有望控制CPC,降低肝内胆管结石术后复发率.AIM：To investigate the application value of celecoxib in treating chronic proliferative cholangitis （CPC）.METHODS：Thirty healthy male SpragueDawley rats were randomly divided into three groups：sham-operation group （n=10）,CPC model group （n=10）,and celecoxib therapy group （n=10）.CPC was induced in rats by inserting a 5-0 nylon suture into the common bile duct up to the porta hepatis retrogradely through the vater papilla.Rats in the sham-operation group only underwent abdominal wall incision and suturing.Celecoxib [50 mg/（kg？d）] was injected into the abdominal cavity of each rat in the therapy group from day 1 after operation.All rats were executed 1 wk after operation.The anti-proliferation activity of celecoxib was evaluated by hematoxylin and eosin （HE） staining,periodic acid-Schiff （PAS） staining,Masson staining and immunohistochemistry staining of the biliary epithelial mucosa,submucosal gland and collagen fiber in the bile duct wall of CPC rats.RESULTS：The proliferative degree of the biliary epithelial mucosa and submucosal gland as well as the fibrotic degree of the biliary wall in the celecoxib therapy group were obviously lower than those in the CPC group,but still higher than those in the sham-operation group.Immunohistochemistry analysis showed that the expression intensity of cyclooxygenase 2 （COX-2） in the celecoxib therapy group was obviously inferior to that in the CPC model group （IA：8.62 ± 0.19 vs 35.27 ± 0.43,P 0.05）,but close to that in the sham-operation group （IA：8.62 ± 0.19 vs 8.41 ± 0.13,P 0.05）.CONCLUSION：By down-regulating COX-2 expression,celecoxib can effectively inhibit the hyperplasia of the biliary epithelial mucosa,submucosal gland,and collagen fiber and reduce the amount of mucous glycoprotein secreted by the submucosal gland,thus holding the promise for controlling CPC and reducing the recurrence of intrahepatic bile duct stones.

关 键 词：慢性增生性胆管炎 塞来昔布 肝内胆管结石 

分 类 号：R657.4[医药卫生—外科学]