多聚ADP-核糖聚合酶抑制剂联合西地那非改善糖尿病大鼠勃起功能的研究

Effect of combination of poly （ ADP - ribose） polymerase inhibitor and sildenafil on erectile function in diabetic rats

目的探讨多聚AOP-核糖聚合酶抑制剂（PJ_34）联合西地那非对糖尿病大鼠勃起功能的影响。方法40只雄性SD大鼠随机分为正常对照组、糖尿病＋西地那非组、糖尿病＋PJ-34组、糖尿病＋PJ-34＋西地那非组。测定各组大鼠阿扑吗啡诱导下的性行为变化；电刺激盆神经测定各组大鼠阴茎海绵体内压（ICP）及平均周围动脉压（MAP），然后取海绵体组织测定Caspase-3活性。结果Caspase-3活性在糖尿病大鼠中显著升高，PJ-34治疗可有效抑制其活性。糖尿病＋西地那非组、糖尿病＋PJ-34组性行为能力及ICP／MA均低于正常对照组，PJ-34与西地那非联合应用疗效显著高于单一用药。结论PJ-34联合西地那非可以显著改善糖尿病大鼠的勃起功能，为糖尿病性勃起功能障碍治疗方法的探索提供了新的思路。

Objective To investigate the effect of combination of poly（ADP - ribose） polymerase （PARP） inhibitor and sildenafil on erectile function in diabetic rats. Methods Forty male SD rats were randomly divided into four groups ： normal control group, diabetic ＋ sildenafil group, diabetic ＋ PJ - 34 group and diabetic ＋ PJ - 34 ＋ sildenafil group. Sexual activity triggered by apomorphine was observed in each group. Mean arterial pressure（MAP） and intracavernous pressure（ICP） induced by electrostimulation of penile dorsal nerves were measured. The corporal tissue was obtained to detect the caspas - 3 activity. Results PARP blockade by PJ - 34 to some extent prevented diabetes - associated apoptosis. The caspas -3 activity was significantly increased in diabetic rats. The sexual activity and ICP/MAP level in diabetic ＋ sildenafil group and diabetic ＋ PJ - 34 group were significantly lower than those in normal control group. The efficiency of combination of PARP inhibitor and sildenafil was significantly higher than single drug application. Conclusion Our results indicate that combination of PARP inhibitor and sildenafil can significantly improve erectile function in diabetic rats, providing experimental groundwork for a new therapeutic intervention for the treatment of diabetes - associated erectile dysfunction.