高胆固醇血症对兔心肌能量代谢的影响及阿托伐他汀和辅酶Q10的干预作用
Effects of atorvastatin and CoQ10 on myocardial energy metabolism in rabbits with hypercholesterolemia
摘要目的 探讨阿托伐他汀和辅酶Q10对高胆固醇血症兔心肌损伤和心肌能量代谢的干预作用.方法40只健康雄性新西兰兔分成5组:正常对照组、高胆固醇组、他汀组、辅酶Q10(5 mg/kg)1组、辅酶Q10(10mg/kg)2组.喂养6周后,取静脉空腹血标本测血清总胆固醇(TC)的浓度;取心肌组织,电镜观察线粒体超微结构改变;用高效液相色谱法测心肌线粒体ATP和辅酶Q10含量;用紫外分光光度法测线粒体呼吸链复合物Ⅱ、Ⅳ的活性.结果高胆固醇组心肌纤维排列紊乱,部分断裂、溶解,线粒体肿胀,嵴紊乱、模糊,与对照组比较,高胆固醇组线粒体呼吸链复合物Ⅱ、Ⅳ活性下降[分别为(μmol·min-1·mg-1)5.39±0.53比12.95±0.99,1.89±0.26比6.65±0.95,P<0.01],线粒体ATP、辅酶Q10含量减少[分别为(mg/L)0.17±0.05比0.44士0.06,0.09±0.02比0.25 ±0.04,P<0.01];他汀组与高胆固醇组比较,呼吸链复合物Ⅱ、Ⅳ活性升高[分别为(μmol·min-1·mg-1)9.12±1.19比5.39±0.53,4.61±0.52比1.89±0.26,P<0.01].线粒体ATP、辅酶Qi0含量差异无统计学意义.辅酶Q101组与他汀组比较,呼吸链复合物Ⅱ、Ⅳ活性差异无统计学意义;线粒体ATP、辅酶Q10含量增加[分别为(mg/L)0.35±0.03比0.16 ±0.04,0.17±0.02比0.07.±0.02,P<0.01].辅酶Q102组与辅酶Q101组比较,各指标差异无统计学意义.结论高胆固醇血症可导致心肌超微结构改变及线粒体能量代谢障碍,阿托伐他汀可减轻心肌结构损伤,阿托伐他汀联合辅酶Q10可进一步改善心肌线粒体能量代谢障碍.
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abstractsObjective To explore the interventional effects of atorvastatin and CoQ10 on myocardial energy metabolism in rabbits with hypercholesterolemia.Methods Forty male New Zealand white rabbits were randomly divided into 5 groups:i.e.normal control,high cholesterol,statin,coenzyme Q10 1 and coenzyme Q10 2.After feeding for 6 weeks,the fasting blood samples were collected through ear marginal vein and the serum level of total cholesterol was determined.Myocardium was sampled for ultrastructures by electron microscopy; high-performance liquid chromatography (HPLC) was used to measure myocardial mitochondria adenosine triphosphate (ATP) and coenzyme CoQ10.Ultraviolet spectrophotometry was used to measure the activities of mitochondrial complexes Ⅱ and Ⅳ.Results In high cholesterol group,myocardial fibers were arrayed disorderly with partial rupture and dissolution.There was mitochondrial swelling with disorderly and fuzzy cristae.As compared with the controls,the activities of mitochondrial respiratory chain complexes Ⅱand Ⅳ declined (5.39 ±0.53 vs 12.95±0.99,1.89 ±0.26 vs6.65 ±0.95,P<0.01),the contents of mitochondrial ATP and CoQ10 decreased (0.17 ± 0.05 vs 0.44 ± 0.06,0.09 ± 0.02 vs 0.25 ±0.04,P <0.01 ) ; for statin group versus high cholesterol group,the activities of mitochondrial respiratory chain complexes Ⅱ and Ⅳ increased (9.12 ± 1.19 vs 5.39 ± 0.53,4.61 ± 0.52 vs 1.89 ± 0.26,P <0.01 ) ; the content differences of mitochondrial ATP and CoQ10 were statistically insignificant.For CoQ10 1group versus statin group,the differences of respiratory chain complexes Ⅱ and Ⅳ were statistically insignificant; the contents of mitochondria ATP and CoQ10 increased (0.35 ±0.03 vs 0.16 ±0.04,0.17±0.02 vs 0.07 ± 0.02,P < 0.01 ).For coenzyme Q10 2 group versus coenzyme Q10 1 group,none of the indices was statistically significant.Conclusion High cholesterol can cause myocardial ultrastructural changes and impaired mitochondrial energy metabolism.Atorvastatin reduces the myocardial structural damage and the combination of atorvastatin and CoQ10 may further improve the myocardial mitochondrial energy metabolism.
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