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Akt/GSK-3β/eNOS 磷酸化介导藏红花醛诱导的大鼠心肌缺血再灌注损伤保护作用。

Akt/GSK-3β/eNOS phosphorylation arbitrates safranal-induced myocardial protection against ischemia-reperfusion injury in rats.

机构信息

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Eur J Nutr. 2012 Sep;51(6):719-27. doi: 10.1007/s00394-011-0251-y. Epub 2011 Oct 9.

DOI:10.1007/s00394-011-0251-y
PMID:21983875
Abstract

PURPOSE

Traditional medicine has been appropriately identified as the most productive soil for the cultivation and harvesting of modern medicines. Herein, we postulate that safranal, an active constituent of Crocus sativus, owing to its strong antioxidant and anti-apoptotic potential, could be a valuable molecule in alleviating myocardial ischemia-reperfusion (IR) injury.

METHODS

To evaluate this hypothesis, safranal (0.1-0.5 mL/kg/day, i.p.) or saline were administered to rats for 14 days, and on 15th day, one-stage ligation of left anterior descending coronary artery for 45 min was performed, followed by 60 min reperfusion.

RESULTS

We concluded that safranal not only significantly decreased infarct size, but also improved left ventricular functions and the overall hemodynamic status of the myocardium. Interestingly, safranal enhanced phosphorylation of Akt/GSK-3β/eNOS and suppressed IKK-β/NF-κB protein expressions in IR-challenged myocardium. Our findings also imply that safranal exhibits strong anti-apoptotic potential, as evidenced by upregulated Bcl-2 expression and downregulated Bax and caspase3 expression with decreased TUNEL positivity. Moreover, safranal dose-dependently normalized myocardial antioxidant and nitrotyrosine levels, cardiac injury markers (LDH and CK-MB), and decreased TNF-α level in IR-insulted myocardium. Histopathological and ultrastructural findings correlated with the functional and biochemical outcomes showing preserved myocardial architecture and decreased inflammatory cells and edema.

CONCLUSIONS

Taken together, these results provide convincing evidence of safranal as an invaluable molecule in myocardial IR setting probably due to its fortified antioxidant and anti-apoptotic potential.

摘要

目的

传统医学已被恰当地确定为现代药物的培育和收获的最有成效的土壤。在此,我们假设藏红花醛,藏红花的一种活性成分,由于其强大的抗氧化和抗细胞凋亡潜力,可能是一种有价值的分子,可以缓解心肌缺血再灌注(IR)损伤。

方法

为了评估这一假设,藏红花醛(0.1-0.5 mL/kg/天,腹腔注射)或生理盐水连续给大鼠注射 14 天,在第 15 天,进行左前降支冠状动脉单阶段结扎 45 分钟,然后再灌注 60 分钟。

结果

我们得出结论,藏红花醛不仅显著减少了梗死面积,而且改善了左心室功能和心肌的整体血液动力学状态。有趣的是,藏红花醛增强了 Akt/GSK-3β/eNOS 的磷酸化,并抑制了 IR 损伤心肌中的 IKK-β/NF-κB 蛋白表达。我们的研究结果还表明,藏红花醛表现出强大的抗凋亡潜力,这表现在 Bcl-2 表达上调、Bax 和 caspase3 表达下调以及 TUNEL 阳性减少。此外,藏红花醛呈剂量依赖性地使心肌抗氧化和硝基酪氨酸水平、心脏损伤标志物(LDH 和 CK-MB)正常化,并降低了 IR 损伤心肌中的 TNF-α 水平。组织病理学和超微结构发现与功能和生化结果相关,显示出保存完好的心肌结构和减少的炎症细胞和水肿。

结论

综上所述,这些结果为藏红花醛作为一种有价值的分子提供了令人信服的证据,可能是由于其强大的抗氧化和抗细胞凋亡潜力。

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