转化生长因子-β转导通路在良性胆管狭窄形成中的作用

目的 观察转化生长因子-β1(TGF-β1)/Smad/结缔组织生长因子(CTGF)通路中各因子在良性狭窄胆管组织中的表达,探讨其信号转导通路在良性胆管狭窄形成机制中的作用.方法 采用免疫组织化学SABC法和原位杂交法检测TGF-β1,TGF-β受体I(TβR Ⅰ),TGF-β受体Ⅱ(TβRⅡ),Smad4,Smad7,CTGF蛋白以及CTGF mRNA在23例良性胆管狭窄组织及6例正常胆管组织中的表达,分别计算阳性表达率,并分析TGF-β1,Smad4及CTGF之间的相关性.结果 TGF-β1、TβR Ⅰ、TβRⅡ、Smad4、CTGF蛋白和CTGFmRNA在23例胆管良性狭窄患者中的阳性表达率分别为91.3%、82.6%、87.O%、78.3%、82.6%、65.2%,高于其在6例正常胆管中的表达且差异有统计学意义(P＜0.05),Smad7在胆管良性狭窄患者中的阳性表达为70.0%,与正常胆管比较升高但差异无统计学意义(P＞0.05).TGF-β1、Smad4及CTGF在良性狭窄胆管的阳性表达呈正相关.结论 TGF-β1/Smad/CTGF信号转导通路高表达是导致良性胆管狭窄形成的重要因素.

Expression of transforming growth factor -β signalling pathway in the benign biliary stricture

Objective To investigate the expression of members of the transforming growth factor 131 (TGF-β1)/Smad/connective tissue growth factor (CTGF) signalling pathway in the tissue of benign biliary stricture and explore their roles in the benign biliary stricture formation.Methods Paraffin-embedded tissues from 23 cases of the benign biliary stricture were analyzed for members of the TGF-β/Smad/CTGF signaling pathway.TGF-β1,TβR Ⅰ ,TβR ,Smad4,Smad7 and CTGF protein were observed by immunohistochemical strepto-advidinbiotin complex method,and CTGF mRNA was detected by hybridization in situ,while 6 cases of normal bile duct served as controls.Positive expression rate was counted respectively.The relativity between TGF-β1 ,Smad4 and CTGF was analyzed.Results The positive expression rate of TGF-β1 ,TβR ,TβR Ⅱ ,Smad4,CTGF protein and CTGF mRNA in 23 patients with benign biliary stricture was 91.3 %,82.6%,87.0% ,78.3 %,82.6% and 65.2% respectively,significantly higher than that in 6 cases of normal bile duct ( P＜0.05).The positive expression rate of Stand7 in the patients with benign biliary stricture was 70.0%,higher than that in patients with normal bile duct,but there was no statistically significant difference ( P＞0.05 ).There was a positive correlation between positive expression of TGF-131 ,Smad4 and that of CTGF in the benign biliary stricture.Conclusion The high expression of TGF-β/Smad/CTGF signalling pathway plays an important role in the process of benign biliary stricture formation.