Total Ginsenosides of Asian Ginseng Increase Coronary Artery Perfusion Flow of the Ischemia-Reperfusion Injury Rat Heart in Langendorff System through Activation of Akt-eNOS Signaling and Cardiac Energy-associate Protein Expression.

摘要

The ischemic heart disease (IHD) is a common human disease and also one of the major causes of death around the world. Any factors that destroy the balance between the demand and the supply of myocardial oxygen can induce IHD. Restoration of blood flow to increase supply of oxygen in heart tissues is the major purpose of treatment for the disease.;Asian ginseng (AG) is the most commonly-used tonic herb to treat IHD and the ginsenosides have been proven as the major active ingredients for its drug actions, such as cardio-protection. In the current study, we examined the effect of total ginsenosides (TGS) on the influence of CPF of the ischemic rat hearts in Langendorff system, and then molecular mechanisms related to vasodilatation induced by TGS were intensively investigated. The results showed that TGS could significantly and dose-dependently increase CPF either in the basal perfusion condition or I/R injury condition. It could improve systolic and diastolic functions of the ischemic hearts as well. The vasodilatation-associated signaling inhibitors, L-NAME, ZnPPIX, ODQ, indomethacin and TEA, could partially abolish the effect of TGS on increasing CPF in rat hearts. In addition, mechanistic studies were performed at both organ and cellular level by using ischemic rat heart tissues and human aortic endothelial cells (HAECs). The results showed that levels of NO and 6-keto-prostaglandin F1a in coronary effluents and supernatants of cell culture of HAECs were significantly elevated by TGS treatment. TGS could elevate the intracellular calcium concentration in HAECs under normoxia and hypoxia/reoxygenation. Also, expression of p-Akt and p-eNOS in the left ventricle tissues of ischemic rat hearts and HAECs under hypoxia/reoxygenation was upregulated by TGS treatment, but without influence on other signaling molecules. Moreover, TGS could up-regulate p38 kinase in the left ventricle tissues of ischemic rat hearts and HAECs but no influence to other kinases in MAPKs signaling pathway. According to the results tested by proteomic technologies, we knew that over 1000 protein spots from left ventricle tissues of the ischemic rat hearts were detected by using 2D-gel image analysis. 11 differentially expressed protein spots were observed in TGS-treated heart tissues, among which 6 proteins related to regulation of the cardiac energy were successfully identified by MALDI-TOF-MS-MS analysis.;In conclusion, TGS significantly increased CPF of the isolated rat hearts in Langendorff system both in the basal perfusion condition and I/R injury condition, indicating that TGS possesses significant potency of dilating coronary arteries and then increases supply of blood and oxygen to the ischemic heart tissues. The action is associated with activation of the Akt-eNOS signaling and regulation of cardiac energy metabolism in the ischemic heart tissues. Thus, TGS might benefit both of the healthy people and patients suffering from ischemic heart conditions.