短链酰基辅酶A脱氢酶在大鼠心脏发育中的表达及其与心肌肥厚的关系

 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1 d、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。

Expression of short-chain acyl-CoA dehydrogenase during heart development in rats and relationship with cardiac hypertrophy

AIM： To investigate the expression of short-chain acyl-CoA dehydrogenase during the heart deve-lopment 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.