Pirfenidone attenuates bladder fibrosis and mitigates deterioration of bladder function in a rat model of partial bladder outlet obstruction

被引:15
作者
Duan, Liu Jian [1 ]
Qi, Jun [1 ]
Huang, Tao [1 ]
Gu, Xin [1 ]
Xu, Ding [1 ]
Kong, Xiang Jie [1 ]
Qian, Xiao Qiang [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Dept Urol, Shanghai 200092, Peoples R China
基金
中国国家自然科学基金;
关键词
bladder fibrosis; extracellular matrix; pirfenidone; partial bladder outlet obstruction; growth factor; GROWTH-FACTOR-BETA; ORAL PIRFENIDONE; GENE-EXPRESSION; LUNG FIBROSIS; III COLLAGEN; DOUBLE-BLIND; ELASTIN; MICE;
D O I
10.3892/mmr.2015.3814
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To investigate the effects of pirfenidone (PFD) on the attenuation of bladder remodeling, and the associated functional changes caused by partial bladder outlet obstruction (pBOO), the present study performed surgery on adult male Sprague-Dawley rats produce a model of pBOO. The rats in the pBOO group were administered a placebo and, in the CMC group, PFD mixed with the placebo was administered orally at 500 mg/kg body weight each day for 5 weeks, from 1 week after surgery. The rat bladders were harvested for biochemical analysis following cystometry at the end of the 6 week period. The histopathology was determined using Masson's trichrome staining. The mRNA and protein levels of pro-fibrotic growth factors and extracellular matrix subtypes were assessed. pBOO debilitated bladder function and caused the parameters from cystometry to increase significantly compared with those in the control group (P< 0.05), which were mitigated significantly following PFD treatment (P< 0.05). In terms of the histology, the rats in the pBOO group exhibited significant increases in bladder weight, muscle hypertrophy and deposition of collagens, which were suppressed by PFD treatment (P< 0.05). Based on the biochemical analysis, significant increases in the mRNA levels of collagen subtypes and growth factors, and protein levels of profibrotic growth factors and a-smooth muscle actin in the bladders of rats in the pBOO group were reduced following PFD treatment. PFD prevented bladder remodeling and attenuated bladder fibrosis and, therefore, mitigated the deterioration of bladder function during the initial stage of pBOO.
引用
收藏
页码:3639 / 3647
页数:9
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