Ling Haiyun, Wu Limao, Li Lianda
Department of Pharmacology on Traditional Chinese Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, PR China.
Phytother Res. 2006 Jun;20(6):448-53. doi: 10.1002/ptr.1875.
The aim of the present investigation was to evaluate the effect of an extract from Corydalis yanhusuo W.T., a Chinese herbal medicine, on ischemia/reperfusion (I/R) injury and to determine the mechanism(s) involved. In rats, the left anterior descending (LAD) coronary artery was occluded for 30 min and then reperfused for 6 h. 0.5% carboxymethyl cellulose sodium was used as a vehicle (I/R control group) and Corydalis yanhusuo rhizoma extract (I/R + CY 200, 100 mg/kg groups) were given. Infarct size and hemodynamic parameters were measured. Apoptosis was detected quantitatively by the terminal transferase dUTP nick end-labeling (TUNEL) method and confirmed by DNA laddering on agarose gel. The expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins was visualized by western blot analysis. In contrast to the I/R control group, administration with CY 200 mg/kg resulted in a significant reduction in the infarct size and an improvement in heart function as evidenced by higher LVSP and +/-dp/dtmax. TUNEL-positive cells in the ischemic myocardium were also significantly reduced in the I/R + CY 200, 100 mg/kg groups, consistent with little DNA laddering in these two groups. Furthermore, greater Bcl-2 and attenuated Bax expression was found in the CY treated rats. These results suggest that the protective effect of Corydalis yanhusuo on myocardial I/R injury is closely associated with the inhibition of myocardial apoptosis through modulation of the Bcl-2 family.
本研究的目的是评估中药延胡索提取物对缺血/再灌注(I/R)损伤的影响,并确定其相关机制。在大鼠中,左冠状动脉前降支(LAD)闭塞30分钟,然后再灌注6小时。以0.5%羧甲基纤维素钠作为赋形剂(I/R对照组),给予延胡索根茎提取物(I/R + CY 200、100 mg/kg组)。测量梗死面积和血流动力学参数。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法对细胞凋亡进行定量检测,并通过琼脂糖凝胶上的DNA梯带进行确认。通过蛋白质免疫印迹分析观察抗凋亡蛋白Bcl-2和促凋亡蛋白Bax的表达。与I/R对照组相比,给予200 mg/kg CY可显著减小梗死面积,并改善心脏功能,表现为左心室收缩压(LVSP)及±dp/dtmax升高。在I/R + CY 200、100 mg/kg组中,缺血心肌中的TUNEL阳性细胞也显著减少,这与这两组中几乎没有DNA梯带现象一致。此外,在CY处理的大鼠中发现Bcl-2表达增加,Bax表达减弱。这些结果表明,延胡索对心肌I/R损伤的保护作用与通过调节Bcl-2家族抑制心肌细胞凋亡密切相关。