胆管良性瘢痕组织中前列腺素F_(2α)受体及前列腺素合酶2的表达及意义

Expressions of Prostaglandin F_(2α) Receptor and Cyclooxygenase-2 in Tissue of Benign Bile Duct Scar and Their Significances

目的探讨前列腺素F2α受体(PTGFR)和前列腺素合酶2(COX-2)在胆管良性瘢痕组织中的表达及意义,并研究转化生长因子-β1(TGF-β1)对胆管成纤维细胞中PTGFR表达的影响。方法收集2008～2010年西安交通大学第一附属医院肝胆外科收治的18例肝外胆管瘢痕性狭窄患者的胆总管组织,另收集6例来自异体肝移植供体的正常胆总管组织作为对照。采用免疫组织化学SABC法分别检测PTGFR及COX-2在两种组织中的表达情况,然后用不同浓度(0、10、20及30ng/ml)TGF-β1作用于胆管成纤维细胞后24h,用半定量RT-PCR法以及ELISA法检测胆管成纤维细胞中PTGFR的mRNA及蛋白表达。结果 PTGFR和COX-2在胆管良性瘢痕组织中的表达阳性率分别为88.9%(16/18)和83.3%(15/18),正常胆总管组织中其表达阳性率分别为33.3%(2/6)及0(0/6),PTGFR及COX-2在前者均分别明显高于后者(P<0.05)。TGF-β1作用于胆管成纤维细胞后24h,随着TGF-β1浓度增高,可上调PTGFR mRNA及蛋白在胆管成纤维细胞中的表达,并且呈浓度依赖性(P<0.05)。结论胆管良性瘢痕组织中PTGFR和COX-2高度表达是造成胆管瘢痕过度增生的重要因素,TGF-β1可诱导胆管成纤维细胞中PTGFR的表达增高,并呈浓度依赖性,调节胆管瘢痕的形成。

Objective To explore the expressions of prostaglandin F2α receptor（PTGFR） and cyclooxygenase-2（COX-2） in tissues of benign bile duct scar and their significances,and investigate the regulating effect of transforming growth factor-β1（TGF-β1） on the expression of PTGFR in human bile duct fibroblasts cultured in vitro. Methods The samples of common bile duct（CBD） scars were collected from 18 patients with benign bile duct scar stricture and 6 cases of normal CBD tissues from liver transplantation donor were collected as control.The expressions of PTGFR and COX-2 were detected by immunohistochemical strept-avidin-biotin complex（SABC） method.Semiquantitative RT-PCR and ELISA methods were used to detect the mRNA and protein levels of PTGFR in bile duct fibroblasts which were effected by TGF-β1 with different concentrations（0,10,20,and 30 ng/ml） for 24 h. Results The positive rates of PTGFR and COX-2 were 88.9%（16/18） and 83.3%（15/18） in tissues of benigh CBD scar and 33.3%（2/6） and 0（0/6） in normal CBD tissues（P〈0.05）.The expressions of the PTGFR mRNA and protein levels became upregulated when the concentrations of the TGF-β1 became higher in human bile duct fibroblasts（P〈0.05）.And the effect was concentration dependant to some extent. Conclusions The high expressions of PTGFR and COX-2 play important roles in the process of benign bile duct stricture formation.TGF-β1 is able to induce higher expressions of PTGFR mRNA level and the PTGFR protein level in a concentration dependent manner,and regulate the formation of benign bile duct stricture.