Basic Research - Infertility & Sexual Dysfunction(구연) (E-024)

쥐 동물 모델에서 고환 허혈 재관류 손상 후 정자 형성에 대한 타다라필의 장기적인 보호 효과
경북대학교 의과대학 비뇨기과학교실
변경현, 강재훈, 이승윤, 민경찬, 하윤석, 김태환, 유은상, 권태균, 이준녕
Tadalafil, phosphodiesterase-5 inhibitors commonly used in the treatment of erectile dysfunction, has recently reported a protective effect against ischemia-reperfusion injury (IRI) in several organs. In this study, we evaluated the long-term protective effect of tadalafil for spermatogenesis in a rat testicular IRI model.
Forty-eight healthy adolescent rats were divided into 6 groups. Sham operation was performed in group A. Group B rats received surgical 720-degree torsion of the left testis for 3 hours without any medication. Groups C, D, E, and F rats were operated surgical torsion for 3 hour with tadalafil at varying doses and durations; group C (low-dose, single administration), group D (low-dose, daily administration), E (high-dose, single administration), and F (high-dose, daily administration). Detorsion was performed after 3 hours of torsion in all rats except the sham group. Four weeks after operation, both testes were harvested for the evaluation of spermatogenesis using Johnsen scoring. To evaluate the protective effect of tadalafil against oxidative stress by IRI, malondialdehyde (MDA) and superoxide dismutase (SOD) level were analyzed via ELISA in both testes 4 hour after detorsion in the same experiments as in group A, B, and C.
Johnsen scores of the left testes for group A through F were 10 ± 0, 2.3 ± 1.2, 4.1 ± 2.9, 5.3 ± 2.3, 4.4 ± 1.8, and 7.4 ± 1.6, respectively. For the evaluation of spermatogenesis according to doses, the groups with high-dose tadalafil showed a higher Johnsen scores than low-dose counterparts (group C, 4.1 ± 2.9 versus group E, 4.4 ± 1.8, p = 0.836; group D, 5.3 ± 2.3 versus group F, 7.4 ± 1.6, p = 0.047). With regard to the administration duration, the groups with daily administration for 4weeks were observed a higher Johnsen scores than those given a single administration (group C, 4.1 ± 2.9 versus group D, 5.3 ± 2.3, p = 0.396; group E, 4.4 ± 1.8 versus group F, 7.4 ± 1.6, p = 0.003). Furthermore, molecular markers related with oxidative stress and histopathologic findings showed remarkable improvement after tadalafil administration for testicular IRI.
Tadalafil alleviated long-term deterioration of spermatogenesis as well as oxidative stress by restoring antioxidant status after testicular IRI rat model. Furthermore, it demonstrated a protective effect against testicular IRI in a time- and dose-dependent manner.
keywords : Spermatic cord torsion, reperfusion injury, phosphodiesterase 5 inhibitors

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