Zheng Dongdan, Liang Qing, Zeng FanFang, Mai Zhuocheng, Cai Anping, Qiu Ruofeng, Xu Rulin, Li Dongjuan, Mai Weiyi
Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.
Department of Emergency Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
Lipids Health Dis. 2015 May 2;14:41. doi: 10.1186/s12944-015-0041-2.
Asymmetric Dimethylarginine (ADMA) is an inhibitor of endogenous nitric oxide synthase, which is the key synthase for nitric oxide (NO) production. Whether statins could protect endothelium by reducing ADMA concentration is unclear, and whether this effect is associated with the dose of statins usage is also needed further studied.
Dyslipidemia rat model was produced by giving high-fat and high-cholesterol diet for 8 weeks. Thereafter, low-dose (5 mg/kg body weight/day) and high-dose (20 mg/kg body weight/day) atorvastatin were orally prescribed for 4 weeks. Parameters of interest including lipid profiles, inflammatory and oxidative markers, NO production and plasma levels of ADMA and ADMA concentration of myocardium were evaluated. Liver enzymes and creatinine kinase (CK) were also detected for safety concern.
At baseline, all parameters were comparable between the sham and the dyslipidemia groups. At 8 weeks of dyslipidemia establishment, as compared to the sham group, body weight and lipid profiles were significantly elevated, and plasma levels of C-reactive protein (CRP), malondialdehyde (MDA) and ADMA were concomitantly increased in accompanying with NO reduction in the dyslipidemia groups. With 4 weeks of atorvastatin therapy, as compared to the control group, lipid disorders and NO production were improved, and plasma levels of CRP, MDA and ADMA were significantly decreased in the high-dose atorvastatin group. ADMA concentration of cardiac tissues was also significantly reduced in the high-dose atorvastatin group. Notably, there was a trend to similar effects which did not reach statistical significance in the low-dose atorvastatin group when compared to the control group. Liver enzyme and CK were comparable after 4 weeks of atorvastatin therapy between groups.
In rats with dyslipidemia, atorvastatin therapy could reduce plasma level of ADMA and ADMA concentration in cardiac tissues, and these effects are associated with the dose of atorvastatin therapy.
不对称二甲基精氨酸（ADMA）是内源性一氧化氮合酶的抑制剂，而内源性一氧化氮合酶是产生一氧化氮（NO）的关键合酶。他汀类药物是否能通过降低ADMA浓度来保护内皮尚不清楚，且这种作用是否与他汀类药物的使用剂量相关也有待进一步研究。
通过给予高脂高胆固醇饮食8周建立血脂异常大鼠模型。此后，口服低剂量（5毫克/千克体重/天）和高剂量（20毫克/千克体重/天）阿托伐他汀4周。评估包括血脂谱、炎症和氧化标志物、NO生成以及血浆ADMA水平和心肌ADMA浓度等相关参数。出于安全性考虑，还检测了肝酶和肌酸激酶（CK）。
在基线时，假手术组和血脂异常组之间的所有参数具有可比性。在血脂异常建立8周时，与假手术组相比，血脂异常组的体重和血脂谱显著升高，同时血浆C反应蛋白（CRP）、丙二醛（MDA）和ADMA水平伴随NO减少而升高。经过4周的阿托伐他汀治疗，与对照组相比，高剂量阿托伐他汀组的血脂紊乱和NO生成得到改善，血浆CRP、MDA和ADMA水平显著降低。高剂量阿托伐他汀组心脏组织的ADMA浓度也显著降低。值得注意的是，与对照组相比，低剂量阿托伐他汀组有类似作用的趋势，但未达到统计学意义。阿托伐他汀治疗4周后，各组之间的肝酶和CK具有可比性。
在血脂异常大鼠中，阿托伐他汀治疗可降低血浆ADMA水平和心脏组织中的ADMA浓度，且这些作用与阿托伐他汀治疗的剂量相关。
