非诺贝特通过上调短链酰基辅酶A脱氢酶抑制大鼠心肌肥厚  

Fenofibrate inhibits cardiac hypertrophy by up-regulation of short-chain acyl-CoA dehydrogenase

作　　者：周四桂[1] 徐立朋[2] 路遥[3] 袁茜[3] 潘雪刁[1] 臧林泉[1] 

机构地区：[1]广东药学院临床药学系,广东广州510006 [2]暨南大学药学院新药研究所,广东广州510632 [3]中山大学中山医学院

出　　处：《中国临床药理学与治疗学》2013年第8期868-873,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金青年科学基金资助项目(81000072;81001683);教育部留学回国启动基金资助项目(23610008);教育部博士学科点专项科研基金资助项目(20104401120003)

摘　　要：目的:研究非诺贝特对自发性高血压大鼠(Spontaneously hypertensive rats,SHR)心肌中短链酰基辅酶A脱氢酶(Short-chain acyl-CoAdehydrogenase,SCAD)的表达、心肌脂质代谢变化以及心肌肥厚指标的影响,探讨非诺贝特改善SHR心肌肥厚的作用机制。方法:观察非诺贝特灌胃8周后,SHR的血压及左室重量指数、血清和心肌游离脂肪酸含量的变化,采用Westernblot方法检测心肌过氧化物酶体增殖剂活化受体α(PPARα)和SCAD的蛋白表达变化,采用厌氧性电子转移黄素蛋白荧光还原分析法检测SCAD酶活性的改变。结果:与Wistar-Kyoto(WKY)大鼠比较,SHR的血压及左室重量指数均明显增高,心肌中PPARα与SCAD的蛋白表达明显下调,SCAD的酶活性显著降低,血清和心肌游离脂肪酸含量增加(P<0.05);与SHR比较,非诺贝特治疗8周后的SHR,其左室重量指数明显下降,血压无明显变化,心肌中PPARα与SCAD的蛋白表达明显上调,SCAD的酶活性显著增高,血清和心肌游离脂肪酸含量减少(P<0.05)。结论:非诺贝特增加心肌中SCAD的蛋白表达,改善心肌能量代谢障碍,可能是其抑制心肌肥厚发生与发展的机制之一。AIM： To investigate the effect of fenofibrate on the expression of short-chain acyl- CoA dehydrogenase （SCAD）, cardiac lipid me- tabolism and cardiac hypertrophy in spontane- ously hypertensive rats （SHR）. METHODS： SHR were given fenofibrate for 8 weeks, then systolic pressure and the ratios of left ventricular weight to body weight, free fatty acid in blood serum and cardiac muscle were measured. The expression of PPARa and SCAD in myoeardium were investigated by western blot. Enzyme ac- tivity of SCAD in myocardium was measured with the anaerobic electron transfer flavoprotein fluoreseenee reduction assay. RESULTS： Com- pared with WKY rats, systolic blood pressure and the ratios of left ventrieular weight to body weight were markedly elevated in SHR. The ex- pression of PPARa and SCAD in myoeardium of SHR were decreased as compared with WKYgroup. The activity of SCAD in myocardium was lower than that in WKY rats. Free fatty acid in blood serum and cardiac muscle were higher than that in WKY rats. Compared with SHR, fenofi- brate decreased the ratios of left ventricular weight to body weight, but had no effect on sys- tolic blood pressure. After treated with fenofi- brate, the expression of PPAR and SCAD in myocardium of SHR was increased in associated with lower contents of free fatty acid in blood se- rum and cardiac muscle. CONCLUSION.. Fenofi- brate may ameliorate cardiac hypertrophy by in- creasing the expression of SCAD and improving cardiac energy metabolism in SHR.

关 键 词：非诺贝特 心肌肥厚 过氧化物酶体增殖物激活受体Α 短链酰基辅酶A脱氢酶 脂肪酸氧化 

分 类 号：R965.2[医药卫生—药理学]