Ma Li-ping, Kang Ma-fei, Yin Song-mei, Nie Da-nian, Xie Shuang-feng, Wu Yu-Dan, Li Yi-qing, Feng Jian-hong, Xu Li-zhuo
Department of Hematology, Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Zhonghua Xue Ye Xue Za Zhi. 2005 Sep;26(9):539-42.
To observe the effects of pravastatin on platelet-derived nitric oxide system in hypercholesterolemia (HC) and atherosclerosis (AS) in rabbits, and the relationship between these changes and atherosclerosis courses.
Thirty male New Zealand white rabbits were randomly divided into three groups, 12 in group A, 12 in group B, and 6 in group C. All of them were fed daily with cholesterol-rich food during the first 12 weeks. In addition, in group A, pravastatin (10 mg) was orally administered daily. At the end of the 12th week, 6 in group A and B were killed randomly and their aortas were removed and the pathologic changes were observed. In the following 12 weeks, food enriched with cholesterol was substituted with normal food in all three groups. Pravastatin treatment was continued or started in the remaining members of group A and group B, but not in group C. At the end 24th week, all rabbits were killed and their aortas were examined for the fatty-streaks or atherosclerotic plaques. The expressions of endothelial NOS (eNOS) mRNA and inducible NOS (iNOS ) mRNA, NOS activity, NO production and the level of the serum lipids were measured at 0, 6th, 12th, 18th and 24th week.
The expression levels of platelet-derived NOS mRNA, eNOS mRNA ratio in group A had no difference at above time points, while in group B were reduced significantly at 6th week and 12th week compared with at 0 week (P <0.01), and increased at 18th week and 24th week compared with 12th week (P <0.05). The expression levels of eNOS mRNA in group C were reduced at 6th, 12th and 18th, 24th week compared with 0 week (P <0.05 and P <0.01, respectively), and were reduced in groups B and C compared with group A at 6th ,12th week (P < 0.05) and increased in group A and B compared with group C at 18th, 24th week (P <0.01). The expression levels of iNOS/mRNA among the three groups had no difference. Pathologic finding of the arteries: AS was not found in group A from the 12th to 24th week. While in group B, there were a lot of fatty-streaks on the entire intima of all large arteries at the 12th week. There were also fatty-streaks in the ascending aorta, but were improved at the 24th week. In group C, there were marked plaques in the entire aorta at the 24th week.
The expressions of platelet-derived eNOS mRNA, NOS activity, NO production are decreased in HC or AS rabbits. Pravastatin can up-regulate expressions of platelet-derived eNOS mRNA, NOS activity, leading to preventing or improving the pathological courses of AS.
观察普伐他汀对兔高胆固醇血症（HC）和动脉粥样硬化（AS）血小板源性一氧化氮系统的影响，以及这些变化与动脉粥样硬化病程的关系。
30只雄性新西兰白兔随机分为三组，A组12只，B组12只，C组6只。在最初12周内，所有兔子每日喂以富含胆固醇的食物。此外，A组每日口服普伐他汀（10mg）。第12周结束时，随机处死A组和B组各6只兔子，取出主动脉，观察病理变化。在接下来的12周内，三组均将富含胆固醇的食物换为正常食物。A组和B组剩余兔子继续或开始普伐他汀治疗，C组不进行治疗。第24周结束时，处死所有兔子，检查主动脉有无脂肪条纹或动脉粥样硬化斑块。在第0、6、12、18和24周测量内皮型一氧化氮合酶（eNOS）mRNA和诱导型一氧化氮合酶（iNOS）mRNA的表达、一氧化氮合酶活性、一氧化氮生成及血脂水平。
A组血小板源性一氧化氮合酶mRNA表达水平、eNOS mRNA比值在上述时间点无差异，而B组在第6周和第12周时较第0周显著降低（P<0.01），在第18周和第24周时较第12周升高（P<0.05）。C组在第6、12、18和24周时eNOS mRNA表达水平较第0周降低（分别为P<0.05和P<0.01），在第6、12周时B组和C组较A组降低（P<0.05），在第18、24周时A组和B组较C组升高（P<0.01）。三组iNOS/mRNA表达水平无差异。动脉病理检查：A组在第12至24周未发现AS。而B组在第12周时所有大动脉内膜均有大量脂肪条纹。升主动脉也有脂肪条纹，但在第24周时有所改善。C组在第24周时整个主动脉有明显斑块。
HC或AS兔血小板源性eNOS mRNA表达、一氧化氮合酶活性、一氧化氮生成降低。普伐他汀可上调血小板源性eNOS mRNA表达、一氧化氮合酶活性，从而预防或改善AS的病理进程。
