尿道下裂术后尿道狭窄细胞生物学基础研究

目的：模拟3种手术方式（TIP、Mathieu、Onlay）对尿道下裂动物模型进行尿道重建,探讨尿道瘢痕转归,为尿道下裂术后尿道狭窄并发症的防治提供理论依据。方法：26只大白兔,分为TIP、Mathieu与Onlay 3个实验组（每组各8只）和对照组（2只）。切除部分尿道腹侧全层,形成尿道下裂模型,分别采用TIP、Mathieu与Onlay术式进行尿道重建。分别于术后5 d、14 d、6周、3月每组各处死2只,肉眼观察有无尿道瘘及尿道狭窄,组织标本行石蜡切片HE染色、Masson胶原三色染色,免疫组织化学检测TGF-β1、α-SMactin细胞阳性表达情况。结果：全部实验兔无伤口感染及尿道狭窄,仅在Onlay组中出现1例尿道瘘。HE染色光学显微镜下观察发现,TIP组术后5 d尿道板及尿道腹侧创面已完全上皮化。Masson胶原三色染色提示Mathieu组与Onlay道腹侧胶原增生显著,增生明显强于TIP组。各组TGF-β1阳性表达以术后14 d、6周最强,组内各期比较差异并无统计学意义;各组α-SMactin阳性表达,以术后5 d最弱,6周、3月最强,组内比较差异有统计学意义;TIP组与Mathieu和Onlay组比较,术后6周、3月TGF-β1与α-SMactin明显减弱。结论：尿道愈合过程中,成纤维细胞和肌成纤维细胞均长时间保持较强活性,可能是尿道下裂术后尿道狭窄形成及加重的病理基础。TIP术式尿道板切口完全上皮化愈合,且尿道腹侧瘢痕增生较Mathieu及Onlay术式少,其重建尿道更符合正常解剖组织结构,是一种较为理想的手术方式。

Cytobiological study of urethral healing following hypospadiac repair

Objective： To evaluate the stricture rates of different hypospadias repairs and compare these characters between TIP and traditional procedures（Mathieu and Onlay）in a hypospadiac rabbit model.Methods： The study compared 26 male white rabbits weighting 3 to 4 kg,of which 2 were controls.In expermental groups,the ventral wall of the penile urethra was excised to create a hypospadias-like defect,mimicking TIP,Mathieu and Onlay to repair the defect.Animals were sacrificed at 5,14 days,6 weeks and 3 months（two each） in each group.Urethral stricture and fistulas were evaluated at autopsy,serial sections of the penis were stained with HE,and Masson trichrome for microscopy,others used for immunohistochemical staining with TGF-β1 and α-SMactin.Results： In the experimental groups,no wounds had been infected nor urethral stricture,only one fistula in Onlay urethroplasty.Microscopic examination of TIP at 5 days showed that the incised area of the dorsal urethra,same as the ventral part,had re-epithelialized.Masson trichrome showed that Mathieu and Onlay had notable collagenous proliferation,had significant difference to TIP.The expression of TGF-β1 in ventral areas were the most highest at 14 days and 6 week,with no significant difference in each group.The expression of α-SMactin were the most highest at 6 weeks and 3 months,had significant difference in each group.The expression of TGF-β1 and α-SMactin were markedly higher in Mathieu and Onlay than that in TIP at 6 weeks and 3 months.Conclusion： Fibrosis reaction,lasting long time in urethra after all three urethroplasties,may be the cytobiological foundation of urethral stricture.TIP presenting less fibrous tissue in ventral urethra than that in Mathieu and Onlay,and entire re-epithelialized urethral mucosa manifested its advantage.