他汀对NO缺乏性高血压大鼠主动脉重构的作用  

Effects of Statins on Aortic Remodeling in NO-deficient Hypertension

作　　者：俞建华[1] 程晓曙[1] 杨人强[1] 刘东[1] 苏海[1] 吴清华[1] 

机构地区：[1]江西医学院第二附属医院心内科,江西南昌330006

出　　处：《高血压杂志》2002年第6期555-558,共4页Chinese Journal of Hypertension

基　　金：卫生厅重大招标课题 (编号 2 0 0 0 178- 17)

摘　　要：目的　观察他汀类药物对NO缺乏性高血压大鼠主动脉重构的作用 ,并探讨其可能作用机制。方法　给予大鼠L NAME(5 0mg·kg-1·d-1,L组 )造成NO缺乏性高血压模型 ,并在该模型上同时给予西立伐他汀 (0 1mg .kg-1·d-1,L +C组 )或辛伐他汀 (辛伐他汀 5mg·kg-1·d-1,L +S组 )干预。 8周后 ,测定主动脉管壁面积 /管腔面积 (W /L)、组织一氧化氮合酶 (NOS)蛋白表达和活性、脂质过氧化 (MDA)水平和血清一氧化氮代谢物 (NOx)水平。结果　对比正常对照组 (C组 ) ,L NAME喂养大鼠出现血压持续升高和主动脉明显重构 ,主动脉壁eNOS ,iNOS蛋白表达及MDA水平显著增高 ,NOS活性低下 ,血清NOx水平明显降低 (P均 <0 0 1) ,然而未对血脂造成明显影响 (P =NS) ;西立伐他汀和辛伐他汀在未降压和降脂的情况下 ,显著减轻主动脉重构 ,降低W /L(P均 <0 0 1) ;显著抑制高血压大鼠主动脉eNOS(P分别 <0 0 5 ,0 0 1)和iNOS过高表达 (P均 <0 0 1) ;同时降低组织MDA含量 ,提高主动脉NOS活性 (P均 <0 0 1) ,但未明显提高血清NOx水平 (P =NS)。结论　他汀在未降脂和降压的情况下 ,减轻NO缺乏性高血压大鼠主动脉重构 。Objective To investigate the effects of statins on aortic remodeling in NO deficient hypertension and the possible mechanisms. Methods Cerivastatin (0 1 mgkg -1 ·d -1 , L+C group) or simvastatin (5 mg·kg -1 ·d -1 , L+S group) was given to NO deficient hypertensive rats induced by L NAME (50 mg.kg -1 ·d -1 , L group). After 8 weeks, aorta remodeling was quantified with ratio of wall to cross section area (W/L). The expression and activity of NOS, MDA in aorta and NOx in serum were measured. Results Compared with controls, administration of L NAME induced persistent hypertension and aortic remodeling; Expressions of eNOS and iNOS protein and MDA content in aorta were increased while NOS activity in aorta and NOx level in serum were decreased. Lipid profile showed little changes of hyperlipidemia. In the absence of lowering effect on SBP and lipid, cerivastatin and simvastatin significantly attenuated aortic remodeling (each P <0 01) and inhibited the overexpressions of eNOS( P <0 05 and 0 01, respectively) and iNOS protein( P <0 01); Meanwhile, MDA content in aorta was reduced and NOS activity was enhanced (each P <0 01) without increasing NOx level in serum ( P =NS). Conclusion Cerivastatin and simvastatin therapy ameliorate aortic remodeling in NO deficient hypertension in the absence of BP and lipid lowering, which may be due to improvement of NO availability and reduction of oxidative damage.

关 键 词：他汀 高血压 主动脉重构 一氧化氮 过氧化 

分 类 号：R544.1[医药卫生—心血管疾病] R972.[医药卫生—内科学]