目的:研究大鼠心脏发育过程中短链酰基辅酶A脱氢酶(short-chain acyl-CoA dehydrogenase,SCAD)的表达变化规律,并探讨其与高血压大鼠心肌肥厚的关系.方法:观察不同时期Wistar大鼠和不同周龄自发性高血压大鼠心肌组织的SCAD蛋白表达及酶活性变化,检测大鼠的血清和心肌游离脂肪酸含量.结果:与胚胎期19 d Wistar大鼠组比较,出生后1d、2周、6周及16周龄Wistar大鼠组心肌的SCAD蛋白表达及酶活性增加,血清和心肌游离脂肪酸含量明显减少,二者之间呈负相关,其中,从2周龄Wistar大鼠组开始差异有统计学意义.与周龄匹配的WKY大鼠组比较,2周龄自发性高血压大鼠组收缩压尚未升高,6周龄及16周龄自发性高血压大鼠组收缩压显著增高；各时点自发性高血压大鼠组的左室重量指数均明显增高,提示自发性高血压大鼠在血压升高之前,已经发生了明显的心肌肥厚.与周龄匹配的WKY大鼠组比较,2周、6周及16周龄自发性高血压大鼠组心肌的SCAD蛋白表达及酶活性明显下降,血清和心肌游离脂肪酸含量明显增加,呈显著负相关.结论:(1) SCAD蛋白表达随大鼠心脏的生长发育逐渐上调,可能与心脏对脂肪酸的利用增加密切相关.(2) SCAD的蛋白表达及其酶活性显著下降,可能是导致自发性高血压大鼠肥厚心肌能量代谢“胚胎型再演”的分子基础.%AIM: To investigate the expression of short-chain acyl-CoA dehydrogenase during the heart development in rats and to analyze the relationship between short-chain acyl-CoA dehydrogenase and cardiac hypertrophy in spontaneously hypertensive rats (SHR). METHODS: The expression and activity of short-chain acyl-CoA dehydrogenase in the hearts of Wistar rats with different ages were measured. Free fatty acids in serum and cardiac muscles were also determined. RESULTS: Compared with the fetal rats of 19 d, the expression and activity of short-chain acyl-CoA dehydrogenase in the postnatal rats of 1 d, 2 weeks, 6 weeks and 16 weeks were increased, and free fatty acids in the serum and myocardium were obviously decreased. The difference began in evidence from the age of 2 weeks. The expression of short-chain acyl-CoA dehydrogenase was significantly up-regulated with negative correlation to free fatty acids in the serum and myocardium during heart development. Systolic blood pressure was similar in 2-week-old SHR and WKY rats, which significantly increased in SHR of 6 weeks and 16 weeks old compared with the age-matched WKY rats. The ratio of left ventricular weight to body weight was markedly elevated in SHR of 2 weeks, 6 weeks and 16 weeks old compared with the age-matched WKY rats, indicating that the appearance of cardiac hypertrophy occurred before the development of hypertension in SHR. Compared with the age-matched WKY rats, the expression and activity of short-chain acyl-CoA dehydrogenase were decreased and free fatty acids in the serum and myocardium were obviously higher in SHR. The expression of short-chain acyl-CoA dehydrogenase was significantly down-regulated with a negative correlation to free fatty acids in the serum and myocardium of SHR. CONCLUSION: The expression of short-chain acyl-CoA dehydrogenase is increased during the heart development, which may be associated with the increase in cardiac fatty acid utilization. The down-regulated expression of short-chain acyl-CoA dehydrogenase in the hypertrophic heart may be responsible for the recapitulation of fetal energy metabolism.
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