Chiu Po Yee, Ko Kam Ming
Department of Biochemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
Biofactors. 2003;19(1-2):43-51. doi: 10.1002/biof.5520190106.
In the present study, we examined the time-dependent changes in the mitochondrial glutathione status and ATP generation capacity in the myocardium as well as the susceptibility of the myocardium to ischemia-reperfusion (IR) injury in female Sprague Dawley rats treated with a single pharmacological dose (1.2 mmol/kg) of schisandrin B (Sch B). Sch B treatment produced a time-dependent enhancement in myocardial mitochondrial glutathione status, as evidenced by increases in myocardial mitochondrial reduced glutathione (GSH) level and activities of glutathione reductase, Se-glutathione peroxidase (GPX) and glutathione S-transferases, with the response reaching maximum at 48 h post-dosing and then declining gradually to the control level at 96 h post-dosing. The enhancement of mitochondrial glutathione status was associated with an increase in myocardial ATP generation capacity, with the value peaking at 72 h post-dosing. These beneficial effects of Sch B on the myocardium was paralleled by a time-dependent decrease in the susceptibility to IR injury, with the maximum protection demonstrable at 48 h post-dosing. The cardioprotection was associated with increases in myocardial GSH level and activities of glutathione antioxidant enzymes (except for GPX whose activity was suppressed) as well as tissue ATP level/ATP generation capacity. The results suggest that Sch B treatment can precondition the myocardium by enhancing the mitochondrial glutathione status and ATP generation capacity, thereby protecting against IR injury.
在本研究中，我们检测了用单药剂量（1.2 mmol/kg）五味子乙素（Sch B）处理的雌性Sprague Dawley大鼠心肌中线粒体谷胱甘肽状态和ATP生成能力的时间依赖性变化，以及心肌对缺血再灌注（IR）损伤的易感性。Sch B处理使心肌线粒体谷胱甘肽状态呈时间依赖性增强，表现为心肌线粒体还原型谷胱甘肽（GSH）水平升高以及谷胱甘肽还原酶、硒谷胱甘肽过氧化物酶（GPX）和谷胱甘肽S-转移酶的活性增加，给药后48小时反应达到最大值，然后在给药后96小时逐渐降至对照水平。线粒体谷胱甘肽状态的增强与心肌ATP生成能力的增加相关，该值在给药后72小时达到峰值。Sch B对心肌的这些有益作用与对IR损伤易感性的时间依赖性降低平行，给药后48小时可显示出最大保护作用。心脏保护作用与心肌GSH水平升高以及谷胱甘肽抗氧化酶（除活性受到抑制的GPX外）的活性增加以及组织ATP水平/ATP生成能力增加有关。结果表明，Sch B处理可通过增强线粒体谷胱甘肽状态和ATP生成能力对心肌进行预处理，从而预防IR损伤。
