左卡尼汀对异丙肾上腺素诱导大鼠心肌肥厚的保护作用及机制研究

摘要

目的 观察左卡尼汀( L-carnitine)对异丙肾上腺素(Iso)诱导的大鼠心肌肥厚的保护作用,并探讨其心肌保护作用的可能机制.方法 应用异丙肾上腺素(Iso)制备SD大鼠心肌肥厚模型.40只健康大鼠,随机分成正常对照组(空白组)、异丙肾上腺素组(Iso组)、左卡尼汀组(L-carnitine组)和普萘洛尔组(propranolol组)各10只.除空白组外各组大鼠均皮下注射(sc)Iso 10 d制成心肌肥厚模型.大鼠饲养到期后,检测心脏功能和心脏重量指数；制备心室肌石蜡切片,行Masson染色,光镜下观察心肌形态；测定大鼠心肌组织中的游离脂肪酸(FFA)、乳酸(LAC)和羟脯氨酸(Hpy)水平.分离心肌细胞进行线粒体膜电位(MMP)的测定.结果 相比Iso组,L-camitine组大鼠心脏功能改善,心脏重量指数降低；光镜下观察:心肌细胞肥大程度较Iso组减轻,心肌纤维排列整齐,胶原纤维增生较少；脂肪酸( FFA)、乳酸(LAC)和羟脯氨酸(Hpy)水平增高；心肌线粒体膜电位升高.结论 应用L-camitine在一定程度上可以抑制心肌肥厚的发展,其机制可能与改善能量代谢和细胞线粒体的功能有关.%Aim To investigate the potential effect of L-carnitine in myocardial hypertrophy induced by Iso-proterenol (Iso) in rats and to explore the cardio protective mechanism. Methods The model of myocardial hypertrophy induced by Iso in SD rats was adopted. Forty male rats were randomly divided into four groups: control group, Iso group, Iso + L-carnitine group ( L-camitine group) and Iso + propranolol ( propranolol group) , with 10 rats each group. All except normal control group were made into myocardial hypertrophy by subcutaneous injection of Iso and each group was raised 8 weeks. The tissue of heart was taken to detect calculated heart mass index ( HMI )and left ventricular mass index ( LVMI). The left ventricle myocardium sections were made for Masson dying and were examined by light microscope. The free fatty acids (FFA) , lactic acid ( LAC) and hydroxyproline ( Hpy) were measured. Cardiac cells were isolated to measure themitochondrial membrane potential. Results Compared with Iso group, the heart function, ratio of ventricle weight to heart weight and ratio of heart weight to body weight of L-carnitine group reduced significantly. Results of optical microscope; the level of myocyte hypertrophy was much lower in L-carnitine group, and cells arranged in a good order, collagen fiber proliferated in low level. The lactic acid, free fatty acid and hydroxyproline levels were significantly decreased by L-carnitine. The expression of mitochondrial membrane potential was effectively increased by L-carnitine. Conclusions L-carnitine can inhibit the progress of cardiac hypertrophy. The mechanism may be related to energy metabolism and the protection of myocardial mitochondria.