转化生长因子-β1通过Smad-3对膀胱慢性炎症纤维化的调节作用

Effects of transforming growth factor-β1 and Smad-3 on chronic cystitis and fibrosis

目的 观察转化生长因子-β1（TGF-β1）通过Smad-3对膀胱慢性炎症纤维化的调节作用.方法 将40只SD大鼠随机分为对照组、模型组、大剂量及小剂量干预组.通过尿流体动力学、逆转录-聚合酶链反应（RT-PCR）、苏木素-伊红（HE）及Masson三色染色检测各组差异.结果 与对照组比较,模型组大鼠膀胱慢性炎症纤维化显著,膀胱顺应性由（0.99±0.11） ml/mmHg降低为（0.29±0.05） ml/mmHg,膀胱TGF-β1、Smad-3、Ⅰ型胶原（Collagen Ⅰ）、Ⅲ型胶原（CollagenⅢ）的mRNA表达均显著升高（0.79±0.07、0.73 ±0.06、1.09 ±0.09、1.32 ±0.05,P＜0.05）.两个剂量SB431542干预后,大鼠膀胱顺应性分别增高到（0.64±0.07）和（0.71±0.05） ml/mmHg,Smad-3表达降低为0.30±0.04和0.25±0.05,膀胱炎症及纤维化改善（P＜0.05）.结论 TGF-β1通过调节Smad-3在膀胱慢性炎症及纤维化进程中发挥促进作用.

Objective To evaluate the effects of transforming growth factor-β1 （TGF-β1） and Smad-3 on chronic cystitis and fibrosis.Methods Forty Sprague-Dawley rats were randomized into control group,model group,low dose group and large dose group.Urodynamic detection,real time reverse transcription polymerase chain reaction,hematoxylin and eosin staining and Masson staining were done to determine the difference among the groups.Results As compared with control group,chronic cystitis with diffuse fibrosis in model group was aggravated,bladder compliance was increased [（0.99 ± 0.11） ml/mmHg to （0.29 ± 0.05） m]/mmHg],and the mRNA levels of TGF-β1,Smad-3,Collagen Ⅰ,Collagen Ⅲ increased were significantly （0.79 ±0.07,0.73 ±0.06,1.09 ±0.09,1.32 ±0.05,P 〈0.05）.After administration of two doses of SB431542,bladder compliance was increased significantly [（0.64 ± 0.07） and （0.71 ± 0.05） m]/mmHg],the mRNA levels of Smad-3 decreased significantly （0.30 ± 0.04 and 0.25 ± 0.05）,while the inflammation and fibrosis reduced （P 〈 0.05）.Conclusion TGF-β1 promotes the bladder inflammatory fibrosis probably through the Smad-3 pathway.