摘要
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 effect of short-chain acyl-CoA dehydrogenase（ SCAD） on collagen expression and proliferation of rat cardiac fibroblasts and to explore the relationship between SCAD and cardiac fibrosis.METHODS：The model of proliferation and collagen expression of rat cardiac fibroblasts induced by angiotensin Ⅱ was established.After treatment with siRNA-1186,the expression of SCAD at mRNA and protein levels,fatty acids beta oxidation rate,ATP,the enzyme activity of SCAD and free fatty acids in the rat cardiac fibroblasts were determined.RESULTS：The mRNA and protein expression of SCAD was decreased in the rat cardiac fibroblasts induced by angiotensin Ⅱ compared with the control cells,and the expression of collagen Ⅰ and collagen Ⅲ was significantly upregulated.Compared with negative control group,SCAD expression and activity,fatty acid beta-oxidation rate and ATP significantly decreased in siRNA-1186 group,but the content of free fatty acids were obviously increased in the rat cardiac fibroblasts,and the expression of collagen I and collagen Ⅲ was significantly up-regulated.CONCLUSION：The expression and synthesis disorder of collagen may be triggered by down-regulation of SCAD.SCAD may be a promising therapeutic target for myocardial fibrosis.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2016年第12期2184-2191,共8页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81000072
No.81670239)
广东省科技计划(No.2014A020212315)
广东省自然科学基金资助项目(No.2016A030313729)
广东药科大学"创新强校工程"研究生教育建设项目(No.20140300)
广东省"十二五"医学重点学科
依托广东药科大学附属第一医院
药科学院
