Laboratory of Ethnopharmacology and Institute of Integrated Medicine, Xiangya Hospital, Central South University, Changsha, China.
Tohoku J Exp Med. 2010 Feb;220(2):157-63. doi: 10.1620/tjem.220.157.
Guanxin II (GXII) is a traditional Chinese formula to treat coronary heart disease in China. Previous studies indicate cardioprotection of GXII are related to cardiomyocyte apoptosis. Akt is necessary and sufficient for inhibition of apoptosis in cardiomyocytes. Our aim was to examine whether or not the antiapoptotic mechanisms of GXII are related to the Akt pathway. Male Sprague-Dawley rats were randomly assigned to four groups: GXII administered at 2.5 or 0.5 g raw materials/kg, the vehicle control and sham-operated oral 0.9% NaCl. They were pretreated once a day for 15 consecutive days by gavage. Thirty min after the last administration, the left anterior descending coronary artery was occluded to induce myocardial ischemia except for the sham-operated rats. Compared with rats receiving vehicle, those rats pretreated with GXII at 2.5 g/kg significantly reduced infarct size and decrease apoptosis. Furthermore, GXII (2.5 g/kg) significantly activated Akt kinase, increased the Bcl-2/Bax ratio, inhibited cytochrome c release, reduced caspase-9 activation, and attenuated subsequent caspase-3 activation. GXII at 0.5 g/kg have no noticeable effect on these parameters. Meanwhile, GXII at 2.5 g/kg did not change myocardial blood flow of ischemic zone, indicating a direct action on cardiomyocytes. These results suggest GXII at 2.5 g/kg ensures the survival of myocardium by enhancing the Akt-mediated antiapoptosis pathway. The findings provide new evidence of the effective and safe therapy with GXII for patients with chronic coronary heart disease.
冠心 II 号（GXII）是一种在中国用于治疗冠心病的传统中药方剂。先前的研究表明，GXII 的心脏保护作用与心肌细胞凋亡有关。Akt 对于抑制心肌细胞凋亡是必需且充分的。我们的目的是研究 GXII 的抗凋亡机制是否与 Akt 通路有关。雄性 Sprague-Dawley 大鼠被随机分为四组：2.5 或 0.5 g 生药/kg 的 GXII 给药组、载体对照组和假手术口服 0.9% NaCl 组。它们通过灌胃每天预处理一次，连续 15 天。末次给药 30 min 后，除假手术组大鼠外，其余大鼠的左前降支冠状动脉被结扎以诱导心肌缺血。与接受载体的大鼠相比，接受 2.5 g/kg GXII 预处理的大鼠明显减少了梗死面积和凋亡细胞数。此外，GXII（2.5 g/kg）显著激活了 Akt 激酶，增加了 Bcl-2/Bax 比值，抑制了细胞色素 c 的释放，减少了 caspase-9 的激活，并减弱了随后 caspase-3 的激活。0.5 g/kg 的 GXII 对这些参数没有明显影响。同时，2.5 g/kg 的 GXII 没有改变缺血区的心肌血流，表明其对心肌细胞有直接作用。这些结果表明，GXII 以 2.5 g/kg 的剂量通过增强 Akt 介导的抗凋亡通路来确保心肌的存活。这些发现为慢性冠心病患者使用 GXII 进行有效和安全治疗提供了新的证据。
