Zhang Z, Tang L, Yu W, Chen Y, Dai Y-T
Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
School of Pharmacy, Jiangsu University, Zhenjiang, China.
Andrologia. 2017 Nov;49(9). doi: 10.1111/and.12789. Epub 2017 Mar 10.
The purpose of the present study is to explore the effects of a lipid-lowering drug atorvastatin, a three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in the treatment of erectile dysfunction (ED) in a rat model of atherosclerosis (AS) and the possible mechanisms underneath. A high-cholesterol diet was administrated to Sprague-Dawley rats in an attempt to induce an ASED model, which was later confirmed by abdominal aorta histopathology and erectile function evaluation. ASED rats were further assigned to non-treatment group, atorvastatin low-dose treatment group (5 mg kg day ), high-dose group (10 mg kg day ) and sildenafil (1.5 mg kg day ) treatment group. Lipid profile, erectile function, oxidative stress biochemical markers, endothelial nitric oxide synthase (eNOS) and extracellular superoxide dismutase (SOD ) mRNA expression were evaluated after 8-week treatment duration. Erectile function was impaired in AS rat model, which was preserved in atorvastatin and sildenafil intervention groups. The oxidative stress biochemical markers were attenuated, while eNOS and SOD mRNA expression were restored in atorvastatin and sildenafil groups, which were found to be involved in ED pathogenesis. However, the lipid profile remained unaltered in the treatment group, and it was elevated in ASED rats. This kind of lipid-lowering agent, or atorvastatin, has the utilisation potential in ASED treatment, even before lipid profiles altered. This effect on erectile function preservation of atorvastatin was attributed to its preservation of endothelial function, possibly through amelioration of oxidative stress and improvement in eNOS expression.
本研究的目的是探讨降脂药物阿托伐他汀（一种三羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂）在动脉粥样硬化（AS）大鼠模型中治疗勃起功能障碍（ED）的效果及其潜在机制。对Sprague-Dawley大鼠给予高胆固醇饮食以诱导AS-ED模型，随后通过腹主动脉组织病理学和勃起功能评估进行确认。将AS-ED大鼠进一步分为未治疗组、阿托伐他汀低剂量治疗组（5mg/kg·天）、高剂量组（10mg/kg·天）和西地那非（1.5mg/kg·天）治疗组。在8周治疗期后评估血脂水平、勃起功能、氧化应激生化标志物、内皮型一氧化氮合酶（eNOS）和细胞外超氧化物歧化酶（SOD）mRNA表达。AS大鼠模型的勃起功能受损，而在阿托伐他汀和西地那非干预组中得以保留。氧化应激生化标志物减弱，而阿托伐他汀和西地那非组中eNOS和SOD mRNA表达恢复，这些被发现与ED发病机制有关。然而，治疗组的血脂水平保持不变，而在AS-ED大鼠中升高。这种降脂药物或阿托伐他汀在AS-ED治疗中具有应用潜力，甚至在血脂水平改变之前。阿托伐他汀对勃起功能的这种保护作用归因于其对内皮功能的保护，可能是通过改善氧化应激和提高eNOS表达实现的。
