摘要
目的:探讨辛伐他汀对大鼠心肌梗死后心肌胶原含量的影响及其机制。方法:建立大鼠心肌梗死模型,24h后存活大鼠随机分成心肌梗死组(n=9)、辛伐他汀20mg组[20mg/(kg·d),n=10]和辛伐他汀40mg组[40mg/(kg·d),n=9],另设假手术组(n=10)。4周后观察血脂水平、左心室重量指数和天狼猩红染色分析左心室非梗死区心肌胶原容积分数(表达心肌胶原含量),免疫组化检测基质金属蛋白酶-2(MMP-2),免疫印迹杂交方法(Western blot)和逆转录多聚酶链反应(RT-PCR)检测转化生长因子β1(TGF-β1)在非梗死区的表达。结果:①各组血脂水平差异无统计学意义,心肌梗死组左心室重量指数、非梗死区Ⅰ型、Ⅲ型胶原容积分数及Ⅰ型与Ⅲ型胶原容积分数比值较假手术组均明显升高(P均<0.05),差异均有统计学意义;辛伐他汀两组左心室重量指数、非梗死区Ⅰ型、Ⅲ型胶原容积分数及Ⅰ型与Ⅲ型胶原容积分数比值较心肌梗死组均下降,但仍高于假手术组(P均<0.05),差异均有统计学意义。②心肌梗死组MMP-2和TGF-β1表达较假手术组均显著增加(P均<0.05),而辛伐他汀两组表达则明显降低,但仍高于假手术组(P均<0.05),差异均有统计学意义。结论:辛伐他汀能有效改善大鼠心肌梗死后心肌胶原含量,机制与其调脂作用无关,可能与下调MMP-2和TGF-β1的表达有关。
Objective：Tn investigate the beneficial effects of simvastatin on myocardial collagen changes in rats after myocardial infarction （MI） with its possible mechanisms. Methods ： MI model was created by the ligation of left anterior descending coronary artery. 24 hours after MI, the survival rats were randomly divided into three groups, MI group （n = 9 ）, Simvastatin 20 mg/（ kg · d ）treatment group （n = 10 ）, Simvastatin 40 mg/（ kg · d）treatment group （n = 9 ） ; meanwhile, the Sham-operation group （n = 10 ） was established. After 4 weeks treatment,the effects of simvatatin on ventricular remodeling were evaluated by detecting the changes of left ventrieular weight index （LVWI） ,the collagen volume fraction （CVF） in non-infarction zone （NIZ）was examined with Picric-Sirius Red Polarimetry,the expression of matrix metalloproteinase-2 （MMP-2） by immunohistochcmistry,and the expression of transforming growth factor β1 （TGF-β1） in NIZ by RT-PCR and Western blot analysis. Meanwhile,the serum lipid levels were examined in all groups. Results：There were no significant changes among different groups for serum lipid levels （P 〉 0. 05 ）. Compared with Sham operation group,LVWI,type I CVF,type III CVF and the I/III ratio in NIZ were increased significantly in MI group. Compared with MI group, LVWI, type I CVF ,type III CVF and I /III ratio in NIZ were decreased significantly in both of Simvastatin treatment groups,but higher than those in Sham operation group. In contrast with MI group, the expressions of MMP-2 and TGF-β1 were down regulated in both Simvastatin treatment groups, but higher than those in Sham operation group. Conclusion：Simvastatin could ameliorate MI induced myocardial collagen changes in rats, and this was independent of lipid regulation while it could be associated with down regulated MMP-2 and TGF-β1.
出处
《中国循环杂志》
CSCD
北大核心
2009年第5期344-347,共4页
Chinese Circulation Journal
基金
重庆市自然科学基金资助项目(渝科发计字[2004]54号文)
