Infertility & Sexual Dysfunction(구연) (E-190) 해면체 신경 손상 발기부전 백서 모델에서 SAHA 지속 투여 시 음경해면체 섬유화 차단에 의한 해면체정맥차단기전 이상의 호전: PDE5 억제제와의 비교 ¹한림대학교 강동성심병원, ²서울특별시립 보라매병원, ³서울대학교병원 이정훈¹, 조민철², 손환철², 김수웅³ Purpose: To determine if daily oral administration of suberoylanilide hydroxamic acid (SAHA; a pan-HDAC inhibitor) for 5 weeks from the immediate post-injury period after CN injury would rectify CVOD by suppressing cavernosal fibrosis and normalizing HDAC pathway in a rat model of CN crush injury (CNCI), and to compare the results with those obtained using chronic administration of an oral PDE5 inhibitor (a positive control). Materials and Methods: Fifty-six 12-week-old rats were randomized into the following four groups: sham surgery (S), CNCI (I), and CNCI treated with daily administration of 25.0 mg/kg SAHA (V), and CNCI treated with daily administration of 20.0 mg/kg udenafil (P). The V and P groups received the respective treatment for five weeks from the following day after CNCI. At five weeks after surgery, dynamic infusion cavernosometry (DIC), Masson’s trichrome staining and Western blot were performed. Results: Group I had a significantly decreased papaverine response, higher maintenance or drop rate, lower smooth muscle/collagen ratio, and increased protein expression of HDAC2, HDAC3, TGF-β1 and collagen-1, compared with Group S. The three DIC parameters in Group V and Group P significantly improved compared to those in Group I. Except for maintenance rate, the improvement in papaverine response and drop rate in Group V was not significantly different from that in Group P. Group V and Group P showed the rectification of smooth muscle/collagen ratio, and protein expression of TGF-β1 or collagen-1. Protein expression of HDAC3 was improved in both Group V and Group P, whereas that of HDAC2 was improved only in Group V. Conclusions: Our data indicate that chronic inhibition of SAHA improves CVOD by suppressing cavernosal fibrosis via rectifying HDAC/TGF-β1 pathway in nerve-injured rats. Chronic treatment with SAHA appear to significantly alleviate CVOD, comparable to that with a PDE5 inhibitor. Thus, treatment strategies targeting the HDAC pathway might be helpful to alleviate CVOD induced by CN injury. keywords : Prostatectomy, Fibrosis, Erectile dysfunction