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目的 探讨阿托伐他汀对去甲肾上腺素诱导的心肌肥厚大鼠细胞外基质重塑的影响及其可能的机制。方法 雄性SD大鼠随机分为三组 :(1)对照组 ,(2 )去甲肾上腺素组 [1 0 6mg/ (kg·d)× 15d],(3)去甲肾上腺素 +阿托伐他汀组 [5 0mg/ (kg·d)× 15d]。去甲肾上腺素ip ,2次 /d ,15d ,建立心肌肥厚模型。应用超声心动图及病理学方法评价整体心肌肥厚及组织胶原表达。用逆转录-聚合酶链反应法 (RT PCR)及免疫组化检测细胞外基质调节因子 -基质金属蛋白酶 (MMP - 9)及其生理性抑制剂 (TIMP 1)和转化生长因子 β1(TGF - β1)mRNA和蛋白表达。结果 去甲肾上腺素组大鼠发生左心室肥厚及纤维化 ,胶原含量及MMP 9、TIMP 1和TGF - β1蛋白、mRNA表达显著高于健康对照组 (P <0 0 1)。阿托伐他汀能减少心肌中总体胶原及Ⅰ、Ⅲ型胶原的合成及MMP 9、TGF - β1表达 (P <0 0 1)。结论 MMP 9、TIMP 1和TGF - β1与心肌肥厚大鼠的细胞外基质重塑有关。阿托伐他汀能有效防治心肌纤维化及细胞外基质重塑 ,这一效应与其降低心肌中高表达的MMP 9和TGF - β1有关。
Objective To investigate the effect of atorvastatin on extracellular matrix remodeling induced by norepinephrine in hypertrophic rats and its possible mechanism. Methods Male SD rats were randomly divided into three groups: (1) control group, (2) norepinephrine group [106 mg / (kg · d) × 15d], (3) norepinephrine + Statin group [50mg / (kg · d) × 15d]. Norepinephrine ip, 2 times / d, 15d, establish a model of cardiac hypertrophy. Echocardiography and pathology were used to assess global cardiac hypertrophy and collagen expression. The expressions of MMP - 9, TIMP - 1 and TGF - β1 were detected by reverse transcriptase - polymerase chain reaction (RT PCR) and immunohistochemistry. β1) mRNA and protein expression. Results Left ventricular hypertrophy, fibrosis, collagen content, MMP - 9, TIMP - 1 and TGF - β1 protein expressions in norepinephrine group were significantly higher than those in healthy controls (P <0.01). Atorvastatin can reduce the synthesis of total collagen, type I and type III collagen, and the expression of MMP9 and TGF - β1 in myocardium (P <0.01). Conclusion MMP 9, TIMP - 1 and TGF - β1 are associated with extracellular matrix remodeling in hypertrophic rats. Atorvastatin can effectively prevent and treat myocardial fibrosis and extracellular matrix remodeling, which is related to the decrease of MMP 9 and TGF - β1 in myocardium.