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目的:研究短链酰基辅酶A脱氢酶(short-chain acyl-CoA dehydrogenase,SCAD)在心脏成纤维细胞胶原表达和细胞增殖中的作用,探讨其与心肌纤维化之间的关系。方法:以血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)刺激心脏成纤维细胞建立胶原表达和细胞增殖模型,并采用SCAD的最优干扰序列siRNA-1186进行干扰,检测SCAD的mRNA、蛋白表达、酶活性、脂肪酸β氧化速率、ATP以及游离脂肪酸含量的变化;观察其对心脏成纤维细胞胶原表达和细胞增殖的影响。结果:与对照组相比,在Ang Ⅱ诱导的心脏成纤维细胞增殖和胶原表达模型中,SCAD的mRNA和蛋白表达均显著下调。与阴性对照序列组相比,siRNA-1186干扰后心脏成纤维细胞的SCAD表达和酶活性明显下降,心脏成纤维细胞脂肪酸β氧化速率以及ATP生成明显降低,并且游离脂肪酸含量明显增多。同时,心脏成纤维细胞出现明显增殖,Ⅰ、Ⅲ型胶原的表达明显增加。结论:SCAD表达失调可能导致了心脏成纤维细胞异常增殖、胶原分泌紊乱,上调SCAD可能成为干预心肌纤维化的重要环节之一。
AIM: To investigate the role of short-chain acyl-CoA dehydrogenase (SCAD) in cardiac fibroblast collagen and cell proliferation, and to explore its relationship with myocardial fibrosis. METHODS: Collagen and cell proliferation models were established by stimulating cardiac fibroblasts with angiotensin Ⅱ (Ang Ⅱ). The mRNA and protein expressions of SCAD were detected by siRNA-1186, the optimal interference sequence of SCAD. Activity, fatty acid β oxidation rate, ATP and free fatty acid content were observed. The effect of collagen on cardiac fibroblast collagen and cell proliferation was observed. Results: Compared with the control group, SCAD mRNA and protein expression were significantly down-regulated in Ang Ⅱ-induced cardiac fibroblast proliferation and collagen expression models. Compared with the negative control group, SCAD expression and enzyme activity of cardiac fibroblasts were significantly decreased after siRNA-1186 interference, and the fatty acid β-oxidation rate and ATP production of cardiac fibroblasts were significantly decreased, and the content of free fatty acids was significantly increased. At the same time, cardiac fibroblasts proliferated obviously, the expression of type Ⅰ and type Ⅲ collagen increased obviously. CONCLUSIONS: The imbalance of SCAD may lead to abnormal proliferation of cardiac fibroblasts and disturbance of collagen secretion. Upregulation of SCAD may be one of the important links in the intervention of myocardial fibrosis.