Avaliação do efeito do micofenolato mofetil na túnica albugínea do pênis de ratos após indução da doença de peyronia com TGF- ß

Abstract

Peyronie’s disease (PD) is defined as an acquired fibrosis of the tunica albuginea, which can result in pain, deformity and erectile dysfunction. Currently, PD treatment is controversial because oral therapies present limited efficacy. Aim: : To evaluate the histological, histochemical and stereological changes caused by Mycophenolate Mofetil (MMF) on the tunica albuginea of the rats peniles submitted to TGF-β injection for Peyronie's Disease induction. Methods: Twenty adult male Wistar rats weighing on average 469g were divided into 4 groups. Group Control: animals free of experimental handling; Group 1 TGF-β: animals received injection of TGF-β; Group 2 MMF-7d: animals treated with MMF after 7 days of induction with TGF-β and, Group 3 MMF-30d: animals treated with MMF after 30 days of induction with TGF-β. The measurement of penile curvature was performed before material collecting for histological processing. Penises were photographed and the images measured in computational software. Processing of histological sections was analyzed in conventional light microscope and in fluorescence system coupled with the same microscope. Steorological evaluation included the relative volume of different types of connective fibers of the penile tunica albuginea. Data analysis of penile curvature and stereological evaluation was performed using analysis of variance (ANOVA) and Mann-Whitney test. Results: Firstly, the histochemical assessment showed a fragmentation and a degradation of elastin in the tunica albuginea region. This process was incompletely reversed in the MMF-7d group. In MMF-30d group, a situation very close to normality was observed. An inversion was observed in the colagen III/colagen I ratio with an increase of this ratio in TGF-β and MMF-7d groups, and a decrease in the MIC-30d group approximating to the normality. Penile angle measurement showed decreasing in the mean angle value in the TGF-β group and increasing in the MMF-7d and MMF-30d groups. Conclusion: Intratunical injection of TGF-β was able to promote fibrotic alterations in the region of penile tunica albuginea in Wistar rat, corresponding to PD. In this model of induction of PD in Wistar rat by TGF-β injection, the MMF acts as a regenerating antifibrotic agent. Keywords: Peyronie’s disease, TGF-β, Mycophenolate mophetil