摘要
目的观察阿托伐他汀对动脉粥样硬化兔心肌纤维化的逆转作用并探讨其可能机制。方法将40只新西兰雄性大白兔随机分为动脉粥样硬化组(AS组)、改善饮食组(N组)、他汀干预组(S组)和正常对照组(C组)4组各10只。第一阶段:C组:喂养普通饲料;AS组+N组+S组:开始喂养高脂饲料。8周后C组(n=9)及AS组(n=9)处死大白兔用于实验,证明AS组兔动脉粥样硬化模型建立成功。第二阶段:N组:正常饮食;S组:普通饲料120g/d+阿托伐他汀钙5mg.kg-1.d-1灌胃,8周后用于实验。Masson染色观察兔心肌心肌间质胶原纤维的变化,并测定胶原容积分数(CVF)。免疫组织化学方法检测兔心肌AngⅡ、MMP-1及TIMP-1蛋白表达的水平。结果与C组相比,AS组心肌间质胶原纤维明显排列紊乱,增多增粗,呈条状或不规则网状沉积在心肌间质,部分心肌纤维断裂。AS组CVF显著高于C组,差异有统计学意义(P<0.01);与N组相比,S组CVF显著降低,差异有统计学意义(P<0.01)。与C组相比,AS组AngⅡ及TIMP-1蛋白表达较高,AS组MMP-1蛋白表达显著减少,差异有统计学意义(P<0.05或P<0.01)。与N组比较,S组AngⅡ、TIMP-1蛋白表达较低,MMP-1的蛋白表达较高,差异均有统计学意义(P<0.05或P<0.01)。结论动脉粥样硬化可出现心肌纤维化、RAAS系统激活、TIMP-1表达升高及MMP-1表达降低;阿托伐他汀可逆转心肌纤维化,其机制可能与抑制RAAS从而直接或间接调节MMP-1/TIMP-1的平衡有关。
Objective To observe the effect of atovastatin on reversing myocardial fibrosis in atherosclerotic rabbits and explore the possible mechanism. Methods 40 male New Zeland white rabbits were randomly divided into 4 groups ： atherosclerotic group （AS group）, diet improving group （N group）, atovastatin intervention group（ S group） and normal control group （C group） ,each of 10 rabbits. First stage：C group：fed a normal diet;AS group ＋ N group ＋ S group：high fat diet. After 8 weeks, C group were sacrificed（ n = 9） and AS group（ n = 9 ） rabbits was used in the experiment, proving the rabbit atherosclerotic model successfully established. Second stage： N groups： normal diet; S group： normal diet 120g/d ＋ atorvastatin calcium 5mg . kg -1 . d-1 gavage. After 8 weeks used for the experiment. The change of myocardial interstitial collagen were observed by Masson stained methods, the collagen volume fraction （CVF） was measured. An immunohistochemical investigation of the protein expression of Ang II , MMP-1 and TIMP-1 were performed. Results Compared with C group, the collagen of AS group arranged disorders significantly, the collagen increased, thickened and strip deposition or irregular mesh in the myocardial interstitial and part of collagen fibers fractured. The CVF of AS group was significantly higher than that of C group, the CVF of S group was significantly lower than that of N group, the difference were statistically significant（ P 〈 0.01 ）. Compared with C group,the Ang II and TIMP-1 protein expression of AS group were higher,the MMP-1 protein expression of AS group was significantly lower（P 〈0.05 or P 〈 0. 01 ）. Compared with N group, the Ang II and TIMP-1 protein expression of S group were lower, the MMP-1 protein expression of S group was higher （ P 〈 0.05 or P 〈 0.01 ）. Conclusion There are myocardial fibrosis, activation of RAAS, TIMP-1 expression increased and MMP-1 expression reduced in the progress of atherosclerosis. Atorvastatin can reverse myocardial fibrosis and the mechanism may have a relation with decreasing the activation of the RAAS in myocardium,then accommodate the balance of MMP-1/TIMP-I directly or indirectly.
出处
《临床合理用药杂志》
2012年第31期9-11,共3页
Chinese Journal of Clinical Rational Drug Use
