PDF(Pubmed)
Abstract：
(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect the sildenafil (phosphodiesterase-5 inhibitor)-metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats. (2) Methods: This study involved a cohort of 70 diabetic rats and 10 non-diabetic rats. Diabetic neuropathy was induced by a single dose of 130 mg/kg alloxan. The rats were submitted to thermal stimulus test using a hot-cold plate and to tactile stimulus test using von Frey filaments. Moreover, at the end of the experiment, the animals were sacrificed and their brains and livers were collected to investigate the impact of this combination on TNF-α, IL-6, nitrites and thiols levels. (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in the von Frey test, hot plate test and cold plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect on alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.
摘要：
（1）背景：全球，大约有6亿人患有糖尿病，它最常见的并发症之一是神经病变，衰弱的状况。目前,探索减轻糖尿病神经病相关疼痛的新疗法确实令人着迷，考虑到目前的治疗方案的特点是疗效差，副作用的风险很大。在目前的研究中,我们评估了西地那非(磷酸二酯酶-5抑制剂)-二甲双胍(降血糖药)联合用药在四氧嘧啶诱导的糖尿病神经病变大鼠中的抗痛觉过敏作用及其对四氧嘧啶诱导的生化标志物的影响.(2)方法:本研究包括70只糖尿病大鼠和10只非糖尿病大鼠。单剂量130mg/kg四氧嘧啶可诱发糖尿病神经病变。使用热冷板对大鼠进行热刺激测试，并使用vonFrey丝进行触觉刺激测试。此外，在实验结束时,处死动物，收集它们的大脑和肝脏，以研究这种组合对TNF-α的影响，IL-6、亚硝酸盐和硫醇水平。（3）结果：结果表明，在vonFrey试验中，所有西地那非-二甲双胍组合均降低了疼痛敏感性，热板试验和冷板试验。此外，在对各种西地那非-二甲双胍组合进行15天的治疗后,观察到亚硝酸盐和硫醇浓度以及促炎细胞因子(特别是TNF-α和IL-6)的变化.(4)结论:西地那非与二甲双胍合用对减轻四氧嘧啶诱导的糖尿病神经病变大鼠疼痛具有协同作用。此外,这种组合有效地减少了炎症，抑制NOS活性的上升，并提供防止谷胱甘肽消耗的保护。
