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中药脑必通对急性心肌梗死大鼠的心脏保护作用

钟晗, 辛宏, 朱依谆*   

  1. 复旦大学 药学院 药理学系, 上海 201203
  • 收稿日期:2009-12-10 修回日期:2010-03-15 出版日期:2010-05-15 发布日期:2010-05-15
  • 通讯作者: 朱依谆*

Cardioprotective effects of Chinese herbal medicine Braintone on myocardial infarction in rats

Han Zhong, Hong Xin, Yi-Zhun Zhu*   

  1. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China
  • Received:2009-12-10 Revised:2010-03-15 Online:2010-05-15 Published:2010-05-15
  • Contact: Yi-Zhun Zhu*

摘要: 我们曾经报道过中药脑必通 (Braintone) 的脑保护作用。本研究旨在探索脑必通对Wistar大鼠缺血心肌的保护作用。结扎大鼠冠状动脉前降支两周后, 收集左心室样本进行形态学检测和生化分析。通过对四个实验组死亡率和心脏梗死体积, 毛细血管密度, 抗氧化酶活性, 凋亡相关基因、VEGF和eNOS mRNA表达水平的综合分析, 我们发现脑必通治疗组比模型组有更小的死亡率 (22.2% vs 41.7%) 和心梗体积 (18.0%±3.0% vs 30.4%±9.0%)。同时, 脑必通能增强过氧化氢酶活力 (13.07±0.48 U vs 9.71±0.44 U, P<0.01), 促进抗凋亡基因Bcl-2 和Bcl-xl 的表达 (1.43, 2.30倍, P<0.01), 下调促凋亡基因Bax (0.84倍, P<0.01) 和Caspase-9, Caspase-3的表达。此外, 脑必通治疗组有更高的VEGF和eNOS基因表达水平, 毛细血管密度的增加 (46.0±13.3 vs 27.4±12.6, P<0.01)。研究结果表明脑必通明显改善缺血造成的心肌损伤, 可能通过清除自由基, 抑制心肌细胞凋亡和促进缺血区血管增生等途径发挥保护作用。

关键词: 急性心肌梗死, 脑必通, 活性氧, 细胞凋亡, 血管增生

Abstract: Recently, we reported the unique effects of cerebral protection of the Chinese herbal medicine-Braintone (a formulation containing Radix Rhodiola, Folium Ginkgo, Radix Notoginseng and Rhizoma Ligustici Chuanxiong), also known as Remembrance. In the present study, we tested the hypothesis that Braintone may extend cardioprotective effects on ischemic myocardium in Wistar rats. Animal model was created by ligating of left descending coronary artery. Mortality rate and infarct volume were assessed. In addition, capillary density, antioxidant enzymes, apoptosis modulators and VEGF, eNOS mRNA expression level were investigated to reveal the underlying mechanisms. Treatment with Braintone reduced mortality rate from 41.7% to 22.2% associate with notable diminished infarct volume (30.4%±9.0% vs 18.0%±3.0%). Braintone also acted as antioxidant agent for preserving the activities of catalase (13.07±0.48 U vs 9.71±0.44 U in vehicle, P<0.01). Furthermore, Braintone dramatically boosted the expression levels of anti-apoptotic genes Bcl-2 and Bcl-xl (1.43-, 2.30-fold, P<0.01) as compared to vehicle group and significantly down-regulated the expression level of pro-apoptotic gene Bax (0.84-fold, P<0.01) while slightly inhibited Caspase-9 and Caspase-3 signals. Moreover, higher mRNA expression levels of VEGF and eNOS were observed in Braintone group consisting with a remarkable raise of capillary density (46.0±13.3 vs 27.4±12.6, P<0.01) in myocardium. The findings indicated that Braintone markedly attenuate myocardial damage induced by ischemic insults in vivo. Braintone may confer cardioprotection via scavenging free radicals, inhibiting cardiomyocytes apoptosis and promoting angiogenesis in ischemic region.

Key words: Acute myocardial infarction, Braintone, Reactive oxygen species, Apoptosis, Angiogenesis

中图分类号: 

Supporting:

Foundation item: Pharmacy School of Fudan University (Grant No. kc200602).
*Corresponding author. Tel.: 86-21-51980018; fax: 86-21-51980008