Department of Medicine, University of Melbourne, Austin Health, Australia.
J Atheroscler Thromb. 2012;19(8):705-11. Epub 2012 Jul 27.
In vivo evidence for the pleiotropic effects of simvastatin on the nitric oxide synthase system is limited.
To determine if simvastatin can affect the endothelial nitric oxide synthase cascade.
New Zealand white rabbits (n=15) were divided: Group 1 (control) was fed a normal rabbit diet; Group 2 (MC) received a normal rabbit diet with 1% methionine (M) plus 0.5% cholesterol (C) and 5% peanut oil (atherogenic diet); Group 3 received the same diet as the MC group plus 5 mg/kg/ day simvastatin (S) orally (MCS). After 4 weeks, the abdominal aorta was collected and analyzed.
Total cholesterol (TC) and total homocysteine (tHcy) were not significantly different between MCS and MC. Endothelial function was only reduced in MC (p<0.05). Although eNOS significantly increased in MC and MCS (p<0.01), simvastatin treatment significantly reduced endothelial caveolin-1 by 35% (p=0.038), causing a 2.5-fold (p=0.026) increase in the eNOS: caveolin-1 ratio. The phosphorylation of eNOS at the threonine 495 site or serine 1177 site was not affected by diet or treatment; however, a positive correlation between the two phosphorylation sites was observed (r(2)= 0.5, p=0.01).
in vivo pleiotropic effects of statin therapy include decreasing endothelial caveolin-1. Other therapies designed to affect eNOS phosphorylation in vivo might be useful in further preventing CVD.
关于辛伐他汀对一氧化氮合酶系统的多效性影响的体内证据有限。
确定辛伐他汀是否能影响内皮型一氧化氮合酶级联反应。
将新西兰白兔（n=15）分为三组：第 1 组（对照组）给予正常兔饮食；第 2 组（MC 组）给予正常兔饮食，同时添加 1%蛋氨酸（M）、0.5%胆固醇（C）和 5%花生油（致动脉粥样硬化饮食）；第 3 组给予与 MC 组相同的饮食，同时每天口服 5mg/kg 辛伐他汀（MCS 组）。4 周后，采集腹主动脉并进行分析。
MCS 和 MC 组之间的总胆固醇（TC）和总同型半胱氨酸（tHcy）没有显著差异。内皮功能仅在 MC 组中降低（p<0.05）。尽管 MC 和 MCS 中内皮型一氧化氮合酶（eNOS）显著增加（p<0.01），但辛伐他汀治疗使内皮小窝蛋白-1减少了 35%（p=0.038），导致 eNOS：小窝蛋白-1 比值增加了 2.5 倍（p=0.026）。eNOS 第 495 位苏氨酸或第 1177 位丝氨酸的磷酸化不受饮食或治疗的影响；然而，两个磷酸化位点之间存在正相关（r²=0.5，p=0.01）。
他汀类药物治疗的体内多效性效应包括降低内皮小窝蛋白-1。其他旨在影响体内 eNOS 磷酸化的治疗方法可能有助于进一步预防 CVD。
