阿托伐他汀对老年大鼠多器官内皮型一氧化氮合酶的影响及其在心肌缺血再灌注中的作用  

Effect of atorvastatin on eNOS synthesis in organs of aging rats with myocardial ischemia-reperfusion

作　　者：张今尧[1] 王浩[2] 叶平[2] 

机构地区：[1]解放军总医院海南分院,海南三亚572013 [2]解放军总医院,北京100853

出　　处：《南方医科大学学报》2012年第12期1708-1712,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(30872713)~~

摘　　要：目的观察阿托伐他汀对多器官内皮型一氧化氮合酶(eNOS)合成及eNOS mRNA表达的影响,探讨阿托伐他汀在心肌缺血再灌注过程中对多器官保护作用的可能机制。方法 20月龄Wistar大鼠应用阿托伐他汀灌胃至24月龄,采用结扎冠状动脉方法建立心肌缺血再灌注模型,并设立未用药未手术组、未用药手术组、用药未手术组及用药手术组。应用Western blot方法检测eNOS在各组大鼠心、肝、肾组织的含量,应用RT-PCR方法检测eNOS mRNA的表达情况。同批次同处理24月龄大鼠,分为大剂量他汀组、小剂量他汀组并老年对照组。采用同上方法检测eNOS在各组大鼠心、肝、肾组织的含量,应用Western blot方法检测eNOS在各组大鼠心、肝、肾组织的含量,应用RT-PCR方法检测eNOS mRNA的表达情况。结果阿托伐他汀能显著提高老年大鼠心、肝、肾器官内eNOS合成(P<0.05)及eNOS mRNA的表达(P<0.05),且与心肌缺血再灌注无关。引入药物剂量分组后,与老年对照组相比,他汀组eNOS合成及eNOS mRNA的表达显著增加(P<0.05);其中,大剂量他汀组较小剂量他汀组增加更为显著(P<0.05)。结论阿托伐他汀可使老年大鼠多器官内eNOS合成及eNOS mRNA的表达增加,部分解释了阿托伐他汀在心肌缺血再灌注过程中对多器官功能的保护作用。Objective To observe the effect of atorvastatin on eNOS synthesis in the vital organs of aging rats and explore its mechanism for protection against myocardial ischemia-reperfusion injury. Methods Twenty-month-old Wistar rats were given daily atorvastatin lavage for 4 months. Myocardial ischemia-reperfusion model was established by ligating the coronary artery. The rats were randomized into normal control group, untreated model group, medication without surgery group, and atorvastatin-treated surgical group. The content of eNOS in the heart, liver and kidneys was detected by Western bloting, and eNOS mRNA expression by RT-PCR. The effects of different doses of atorvastatin on eNOS expressions were also evaluated. Results Atorvastatin significantly promoted eNOS synthesis in the heart, liver and kidney of the rats （P〈0.05） regardless of myocardial ischemia-reperfusion. A higher dose of atorvastatin caused a more obvious increase of eNOS protein and mRNA expression in the vital organs of the aging rats （P〈0.05）. Conclusion Atorvastatin can increase eNOS synthesis in the vital organs of aging rats, which partially explains the organ-protective effect of atorvastatin against myocardial ischemia- reperfusion.

关 键 词：老年 阿托伐他汀 缺血再灌注 内皮型一氧化氮合酶 

分 类 号：R965[医药卫生—药理学]