TGF-β1在复发性尿道狭窄发生中的作用

Effect of transforming growth factor β1 in recurrent urethral stricture

目的研究复发性尿道狭窄组织的病理学特点,观察转化生长因子-β1(TGF-β1)在其组织中的表达和分布,探讨其在复发性尿道狭窄形成过程中的作用及意义。方法收集手术切除的复发性尿道狭窄段组织11例以及脑死亡患者的正常尿道组织5例作为研究标本。分别对标本行苏木精-伊红染色、胶原纤维染色、弹力纤维染色和免疫组织化学法检测胶原纤维、弹力纤维的分布、含量和TGF-β1的表达,并与5例正常尿道组织进行对照研究。结果复发性尿道狭窄段组织以大量致密的纤维结缔组织代替海绵体组织,二者互相交错,无明显分界;细胞外基质中胶原纤维增多,弹性纤维减少。复发性尿道狭窄段组织中TGF-β1蛋白为高表达,阳性表达率100%,主要表达于成纤维细胞及血管内皮细胞。正常尿道组织中TGF-β1为低表达,阳性表达率仅为20.0%。两组比较差异有显著性(P<0.05)。结论复发性尿道狭窄组织中的成纤维细胞增殖旺盛、细胞外基质过度沉积形成增生性瘢痕是导致尿道再次狭窄的主要原因,TGF-β1高表达和尿道增生性瘢痕形成关系密切,抑制TGF-β1过度表达将有助于预防和降低尿道再次狭窄的发生率。

Objective To explore the pathological features of recurrent urethral stricture tissues, and to observe the expression of transforming growth factor β1 （TGF-β1） and discuss its role and implication in the process of recurrent urethral stricture formation. Methods The urethral tissues were from 11 patients of recurrent urethral stricture and from 5 patients of brain death. Collagen fibers and elastic fibers were observed by Van Gieson staining, Verhoeff staining, Periodic acid Schiff staining in urethral tissue sections. TGF-β1 in urethral tissues was assessed by immunohistochemical method. Results In comparison with normal urethral tissues, the findings in recurrent urethral stricture tissues revealed that the normal cavernous body tissues were replaced by densely packed connective tissue fibers, collagen fibers increased and elastic fibers reduced. TGF-β1 staining in the tissues of the recurrent urethral stricture was found at the fibroblasts and endothelial cells of blood vessels, with its mean positive rate of 100% but only 20% in normal urethral tissues （P 〈 0.05 ）. Conclusion Active proliferation of fibroblasts and over-deposition of extracellular matrix cause recurrent urethral stricture. High expression of TGF-β1 was related closely with the urethral hyperplastic scar. Inhibiting TGF-β1 could prevent and decrease the process of recurrent urethral stricture.