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首页> 外文期刊>The journal of sexual medicine >Edaravone ameliorates diabetes-induced dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the rat.
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Edaravone ameliorates diabetes-induced dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the rat.

机译：依达拉奉改善了糖尿病引起的NO诱导的大鼠海绵体平滑肌松弛的功能障碍。

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INTRODUCTION: Diabetes mellitus (DM) represents a major risk factor for erectile dysfunction (ED). Although the etiology of diabetes-induced ED is multifactorial and still unknown, reactive oxygen species are thought to be one of the key factors. AIM: The aim of this article is to investigate whether administration of edaravone, a free radical scavenger, could prevent type 1 diabetes-induced dysfunction of nitric oxide (NO)-induced relaxation in corpus cavernosum smooth muscle in the rat. METHODS: Six-week-old male Wistar rats were randomly divided into three groups. One group was treated with citrate-phosphate buffer plus normal saline (group Cont), whereas in the other two groups, diabetes was induced by streptozotocin (50 mg/kg intraperitoneally [i.p.]). Subsequently, the diabetic rats were treated for 4 weeks either with edaravone (10 mg/kg/day, i.p.; group DM + E) or with normal saline (group DM). MAIN OUTCOME MEASURES: Serum glucose and malondialdehyde levels as well as penile cyclic guanosine monophosphate (cGMP) concentrations were determined, and penile function was estimated by organ bath studies with norepinephrine-mediated contractions and acetylcholine-mediated relaxations. The participation mRNA levels of muscarinic M(3) receptors, neuronal nitrous oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS), and participation protein levels of nNOS, eNOS, phosphorylated nNOS, and phosphorylated eNOS were investigated by quantitative real-time polymerase chain reaction (PCR) and immunoblot analysis, respectively. RESULTS: Treatment with edaravone prevented partially but significantly the decreased body and penile weight induced by diabetes. Treatment with edaravone significantly improved the increased diabetes-induced malondialdehyde levels, the decreased penile cGMP concentrations, the increased diabetes-induced norepinephrine-mediated contractions, and the decreased acetylcholine-mediated relaxation. Although there were no significant differences in expression levels of mRNAs in nNOS, diabetes-induced upregulation of muscarinic M(3) receptor and iNOS mRNAs as well as diabetes-induced downregulations of eNOS, phosphorylated nNOS, and phosphorylated eNOS were significantly prevented by edaravone. CONCLUSIONS: Edaravone decreases the oxidative insult in the penile corpus cavernosum by ameliorating the NO-NOS system and thus preventing partially the developing ED in DM in the rat.
机译：简介糖尿病（DM）是勃起功能障碍（ED）的主要危险因素。尽管糖尿病引起的ED的病因是多因素的，但仍然未知，但是活性氧被认为是关键因素之一。目的：本文的目的是研究给予依达拉奉（一种自由基清除剂）是否可以预防1型糖尿病引起的一氧化氮（NO）引起的大鼠海绵体平滑肌松弛的功能障碍。方法：将六周大的雄性Wistar大鼠随机分为三组。一组用柠檬酸盐-磷酸盐缓冲液加生理盐水治疗（Cont组），而其他两组则由链脲佐菌素（腹膜内注射50 mg / kg）诱导糖尿病。随后，用依达拉奉（10mg / kg /天，腹膜内注射; DM + E组）或生理盐水（DM组）治疗糖尿病大鼠4周。主要观察指标：测定血清葡萄糖和丙二醛水平以及阴茎环鸟苷单磷酸（cGMP）的浓度，并通过器官浸浴研究，通过去甲肾上腺素介导的收缩和乙酰胆碱介导的舒张来评估阴茎功能。毒蕈碱型M（3）受体，神经元一氧化二氮合酶（nNOS），内皮型一氧化氮（eNOS）和诱导型一氧化氮（iNOS）的参与mRNA水平和nNOS，eNOS，磷酸化nNOS和磷酸化eNOS的参与蛋白水平进行了研究。实时定量聚合酶链反应（PCR）和免疫印迹分析。结果：依达拉奉治疗可部分预防糖尿病，但可显着降低糖尿病引起的体重和阴茎重量下降。依达拉奉治疗可显着改善糖尿病引起的丙二醛水平升高，阴茎cGMP浓度降低，糖尿病引起的去甲肾上腺素介导的收缩增加，乙酰胆碱介导的舒张性降低。尽管nNOS中的mRNA表达水平无显着差异，但依达拉奉可预防糖尿病引起的毒蕈碱M（3）受体和iNOS mRNA的上调以及糖尿病引起的eNOS，磷酸化的nNOS和磷酸化的eNOS的下调。结论：依达拉奉可通过改善NO-NOS系统而减少大鼠DM中ED的发育，从而减少阴茎海绵体的氧化损伤。

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