Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai 201203, China.
Phytomedicine. 2010 Aug;17(10):753-9. doi: 10.1016/j.phymed.2010.01.018. Epub 2010 Feb 24.
The present study was designed to investigate the protective effects of 4-guanidino-n-butyl syringate (leonurine), a compound in Herba Leonuri (HL) on ischemic rat heart to determine the protective mechanisms associated with ischemic rat hearts. Rat heart ischemia was induced by ligation of the left coronary artery. Creatine kinase (CK) and lactate dehydrogenase (LDH) in plasma and superoxide dismutase (SOD) activity in heart homogenates were measured. We found leonurine significantly decreased levels of LDH and CK activities in plasma. This observation corresponded with decreased infarct size of ischemic rat heart induced by ligation of the left coronary artery. Moreover, the mRNA expression of the pro-apoptotic gene Bax was significantly down-regulated by 0.68-fold (p < 0.05) and the anti-apoptotic gene Bcl-2 was up-regulated by 1.41-fold (p < 0.05) in the leonurine treated groups as compared with acute myocardium ischemia (MI) controls measured by RT-PCR. Correspondingly, Bcl-2 and Bax protein levels detected by Western blotting coincided with gene expression levels. In addition, the mRNA expression level of the antioxidant enzyme Mn-SOD was significantly increased 1.23-fold (p < 0.05) and this finding corresponded with an observed increase in SOD activity and also with a committed decrease in lipid peroxidation. Taken together, our results demonstrated that leonurine attenuated myocardium injury during MI via antioxidative and anti-apoptotic effects and leonurine might become a useful adjuvant cardioprotective agent.
本研究旨在探讨钩吻素丁(一种益母草中的化合物)对缺血性大鼠心脏的保护作用,以确定与缺血性大鼠心脏相关的保护机制。通过结扎左冠状动脉诱导大鼠心脏缺血。测定血浆肌酸激酶(CK)和乳酸脱氢酶(LDH)以及心脏匀浆中超氧化物歧化酶(SOD)的活性。我们发现钩吻素丁可显著降低血浆中 LDH 和 CK 活性。这一观察结果与结扎左冠状动脉引起的缺血性大鼠心脏梗死面积减小相对应。此外,与急性心肌缺血(MI)对照组相比,0.68 倍(p < 0.05)下调促凋亡基因 Bax 的 mRNA 表达,1.41 倍(p < 0.05)上调抗凋亡基因 Bcl-2 的 mRNA 表达,通过 RT-PCR 测定。相应地,通过 Western 印迹检测到的 Bcl-2 和 Bax 蛋白水平与基因表达水平一致。此外,抗氧化酶 Mn-SOD 的 mRNA 表达水平显著增加 1.23 倍(p < 0.05),这一发现与 SOD 活性的增加以及脂质过氧化的明显减少相对应。总之,我们的结果表明,钩吻素丁通过抗氧化和抗凋亡作用减轻 MI 期间的心肌损伤,钩吻素丁可能成为一种有用的辅助心肌保护剂。