机构地区:[1]昆明医科大学第三附属医院微创介入科,云南昆明650118 [2]昆明医科大学附属延安医院口腔科,云南昆明650051 [3]昆明医科大学第二附属医院肝胆胰外二科,云南昆明650101
出 处:《昆明医科大学学报》2017年第12期5-11,共7页Journal of Kunming Medical University
基 金:国家自然科学基金资助项目(81260084)
摘 要:目的探讨紫杉醇壳聚糖缓释膜对兔胆管上皮细胞EMT的抑制作用.方法成功建立新西兰白兔胆管部分离断缝合模型后,40只新西兰白兔随机分为对照组、单纯手术组、未载药壳聚糖缓释膜(SRM)组、紫杉醇壳聚糖缓释膜(PTX-SRM)组4组.各实验组分别于手术后1月从耳缘静脉抽取动物静脉血及取手术缝合处的胆管,测定血清中总胆红素(TBil)、直接胆红素(DBil)、丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST);Masson染色光镜观察损伤胆管胶原蛋白改变;免疫组化检测胆管组织钙粘附蛋白E(E-Cadherin)、平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)的蛋白表达平均光密度(MOD).结果手术后1月各实验组肝功能变化无明显差异(P>0.05);手术组、SRM组中胆管胶原纤维明显增加,PTX-SRM抑制胶原纤维的增加;术后各实验组中E-Cadherin蛋白在胆管上皮细胞内表达均减少,而在间叶组织中表达增强(P<0.05),PTX-SRM抑制胆管上皮细胞E-Cadherin蛋白的减少;术后各实验组中α-SMA、Vimentin蛋白在胆管上皮细胞内表达增强,间叶组织中表达也增强(P<0.05);PTX-SRM抑制胆管上皮细胞α-SMA、Vimentin蛋白表达(P<0.05).结论胆管损伤后胆管上皮细胞发生EMT,参与了胆管瘢痕挛缩的形成;紫杉醇壳聚糖缓释膜具有抑制兔胆管上皮细胞EMT的作用,为治疗胆管瘢痕提供了一种可行性方法.Objective To investigate the inhibitory effect of paclitaxel chitosan membrane in rabbit on EMT ofbile duct epithelial cells. Methods We successfully established the partial bile duct transection of suture model onNew Zealand white rabbits, 40 New Zealand white rabbits were randomly divided into 4 groups: control group,surgery alone group, non drug-loaded chitosan membrane (SRM ) group and paclitaxel chitosan membrane(PTX-SRM ) group. Each experimental group after operation respectively in one month, we extracted animalvenous blood from the ear vein and got surgical suture of bile duct, determinated total bilirubin in serum (TBil ),direct bilirubin ( DBil ) , alanine aminotransferase (ALT ) and aspartate aminotransferase (AST );detected theexpression of E cadherin protein,smooth muscle actin (alpha-SMA), vimentin (Vimentin) in bile duct tissuesby immunohistochemical MOD;observed the collagen changes in injury bile duct by optical microscope on Masson staining. Results No significant different changes in liver function of each experimental group in one month afteroperation (P 〉0.05 );the protein expression levels of E-Cadherin decreased in bile duct cells in all experimentalgroups, while the protein expression in mesenchymal tissue enhanced ( P〈0.05);the protein expression ofalpha-SMA and Vimentin enhanced in bile duct epithelial cells , while the protein expression in mesenchymaltissue enhanced ( P〈0.05);PTX-SRM inhibited the reduction of E-Cadherin protein in bile duct epithelialcells, while inhibited the increasing of alpha-SMA and Vimentin protein( P〈0.05);collagen fiber organizationincreased in operation group,SRM group significantly,while PTX-SRM inhibited the increasing of collagen fiber.Conclusions Bile duct epithelial cells occur EMT after bile duct injury and participate scar contracture of the bileduct. Paclitaxel chitosan membrane can inhibit EMT of rabbit bile duct epithelial cells,and provides a feasiblemethod for the treatment of biliary trac
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