Hypoxia / Reoxygenation Injury With L-carnitine Protective Effect

Myocardial tissue is highly sensitive to hypoxia. Hypoxia is a common pathological process of various types of diseases and is a crucial initiative factor in myocardial function failure induced by shock after severe trauma. Cardiomyocyte necrosis has ever been considered as the main pathological mechanism of ischemialhypoxia. In recent years, the role of apoptosis in pathogenesis of disease of cardiovascular system gradually comes to be known. Some investigations show that apoptosis may be a critical link in heart dysfunction induced by hypoxia, however, there is few report to explore the possible apoptotic effects of hypoxia in cultured cardiomyocytes, let alone to investigate the molecular mechanisms of hypoxialreoxygenation-induced damage. The main way to supply energy for cardiomyocytes is the fatty acid P oxidation in the presence of oxygen in mitochondria, but not the glucose oxidation. This special energy supply manner determines that myocardium is highly sensitive to hypoxialreoxygenation and the important role of fatty acid P oxidation in cardiomyocytes. Studies in recent years show that the disturbances of energy metabolism in cardiomyocytes during hypoxia may be in related to those factors such as oxygen free radical, Ca2 overload in cytoplasma and mitochondria etc. In the process of fatty acid metabolism, long chain fatty acid and acetyl coenzyme (CoA) bind to generate acyl CoA, the fatty acid activation reduction proceed in cytoplasma, but those enzymes needed in this process locates in matrix of mitochondria, therefore, the activated acyl CoA should be transferred in to mitochondria so that it can be utilized. Long chain acyl CoA with the help of L-Carnitine (L-Car) as a carrier therefore enters into mitochondria. L-Car is distributed widely among tissues and has been well established as an essential cofactor for the transport of long-chain acyl CoA through the inner mitochondrial membrane in different types of tissue. Carnitine palmitoyltransferase- II is one of the crucial rate-limiting enzyme during the process of fatty acid P oxidation which is located in matrix side of inner mitochondrial membrane, its function is to catalyse acylCoA-carnitine compound into carnitine and acyl CoA,therefore, the normal oxygen supply, L-Car and CPT- II are three essential factors for maintaining cell energy metabolism. The synthesis of L-Car mainly lies in liver and spleen and has entensive biological function. Studies in recent years show that L-Car can excert protective effect on microcicultory disorder, improve blood supply and prevent the augmentation of the area of necrosis etc. But the protective effect of L-Car on in vitro cultured cardiomyocytes treated with hypoxialreoxygenation and its mechanism has not been fully elucidated. In the present study we use in vitro cultured cardiomyocytes model to investigate protective effects of L-Car on hypoxialreoxygenation and its possible mechanism. The main results were described as follows: 1. Hypoxia excerts significant inhibition on cardiomyocyte proliferation, the longer hypoxia time, the lower the cell proliferation will be. Compared with control, beginning at 8 hour post hypoxia, cell proliferation decreases significantly (p