摘要
目的研究人参茎叶皂苷(GSLS)预适应对自发性高血压大鼠(SHR)心肌缺血再灌注损伤(I-R)的保护作用及可能机制。方法SHR于I-R造模前每日1次灌胃给予GSLS50和100mg.kg-1,连续3周,于缺血40min和再灌注30min内测定大鼠血压、心功能和心脏血流动力学指标,生化方法测定心肌ATPase酶、乳酸脱氢酶(LDH)和超氧化物歧化酶(SOD)活性及丙二醛(MDA)和NO含量,镉血红素饱和法测定心肌和肝脏金属硫蛋白(MT)含量,免疫组化方法测定细胞热休克蛋白70(HSP70)表达。结果GSLS50和100mg.kg-1预适应组显著改善I-R损伤SHR的心率、左室内压峰值和左室内压最大变化速率(±dp/dtmax),明显提高心肌ATPase活性,减少LDH漏出,提高心肌SOD活性,增加NO含量,降低MDA含量,增加心肌和肝脏MT含量,增加心肌HSP70阳性细胞百分数。结论GSLS预适应对心肌I-R损伤具有保护作用,其作用机制与改善SHR心肌舒缩功能,改善心肌代谢,增强抗氧化活性和诱导内源性心肌保护物质的释放有关。
AIM To investigate the cardioprotective effects of pharmacological preconditioning with ginseng stem and leave saponin (GSLS) against myocardium ischemia and reperfusion (I-R) injury in spontaneously hypertensive rats (SHR) and its possible mechanisms. METHODS The SHR were subjected to 40 min ischemia followed by 30 min reperfusion, pharmacological preconditioning groups were administered GSLS 50 or 100 mg·kg^-1 for 3 weeks before I-R. The blood pressure, heart rate and parameters of cardiac function and the hemodynamics involving left ventricular systolic pressure (LVSP) and ± dp/dtmax, were recorded continuously through the process of I-R. The activities of ATPase, lactate dehydrogenase (LDH), superoxide dismutase (SOD), and also contents of nitric oxide (NO) and malondialdehyde (MDA) in myocardium were determined by biochemistry methods. The metallo- thionein (MT) content in liver and myocardium was detected, the expression of heat shock protein 70 (HSP70) in myocardium was measured by immunohistochemistry method. RESULTS Compared with I-R model group, GSLS precon- ditioning group significantly improved heart rate, LVSP and ± dp/dtmax in SHR hearts. Furthermore, the activities of ATPase and SOD increased, the release of LDH reduced, and the content of NO increased, while the MDA content decreased in myocardium. The contents of MT in liver and myocardium enhanced and the expression of HSP70 in myocardium increased. CONCLUSION Preconditioning with GSLS has protective effects on I-R injured myocardium in SHR, which may be related to improving the systolic and diastolic function and hemodynamics indexes, promoting antioxidization capacity, and inducing increment of endogenous protective protein MT and HSP70.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2008年第1期42-48,共7页
Chinese Journal of Pharmacology and Toxicology
基金
中国博士后科学基金资助项目(2004036492)~~