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地奥司明预处理可改善大鼠缺血/再灌注后心脏功能并抑制氧化应激。

Diosmin pretreatment improves cardiac function and suppresses oxidative stress in rat heart after ischemia/reperfusion.

机构信息

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India.

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India.

出版信息

Eur J Pharmacol. 2014 Aug 5;736:131-7. doi: 10.1016/j.ejphar.2014.04.026. Epub 2014 Apr 24.

DOI:10.1016/j.ejphar.2014.04.026
PMID:24769512
Abstract

Reperfusion of ischemic tissue leads to the generation of oxygen derived free radicals which plays an important role in cellular damage. Objective of the current study is to evaluate the cardio-protective and antioxidant effect of diosmin on ischemia-reperfusion related cardiac dysfunction, oxidative stress and apoptosis. Diosmin (50 and 100 mg/kg body weight (bw)) was given every day to the rats orally throughout the experimental period. Ischemia/reperfusion protocol was carried out ex vivo using langendorff perfusion method and the cardiac functional recovery was assessed in terms of percentage rate pressure product. Coronary effluents of LDH and CK-MB activities, antioxidant enzyme activities, lipid peroxidation products, activity of TCA cycle enzymes were evaluated. Moreover, in vitro superoxide anion and hydroxyl radical scavenging potential of diosmin was also quantified. Finally, quantitative real-time PCR was used for assessing Bcl-2 mRNA expression in heart. Cardiac functional recovery was impaired after reperfusion compared with continuously perfused heart. It was significantly prevented by diosmin treatment. Impaired antioxidant enzyme activities and elevated lipid peroxidation products level were also significantly suppressed. The activity of TCA cycle enzymes was protected against reperfusion stress. Down regulated Bcl-2 was also significantly increased. This study concluded that diosmin pretreatment prevents all the impaired patterns including cardiac function, oxidative stress and apoptosis associated with reperfusion in control heart by its antioxidant role.

摘要

缺血组织的再灌注导致氧衍生自由基的产生,这在细胞损伤中起着重要作用。本研究的目的是评估地奥司明对缺血再灌注相关心功能障碍、氧化应激和细胞凋亡的心脏保护和抗氧化作用。地奥司明(50 和 100mg/kg 体重)每天通过口服给予大鼠,贯穿整个实验过程。使用 Langendorff 灌流法在体进行缺血/再灌注方案,以压力产物百分比的形式评估心脏功能恢复。评估了冠状动脉流出液中的 LDH 和 CK-MB 活性、抗氧化酶活性、脂质过氧化产物、TCA 循环酶的活性。此外,还定量了地奥司明的超氧阴离子和羟自由基清除能力。最后,使用实时定量 PCR 评估心脏中 Bcl-2 mRNA 的表达。与持续灌流心脏相比,再灌注后心脏功能恢复受损。地奥司明处理显著预防了这种情况。受损的抗氧化酶活性和升高的脂质过氧化产物水平也得到了显著抑制。TCA 循环酶的活性也受到再灌注应激的保护。下调的 Bcl-2 也显著增加。这项研究得出结论,地奥司明预处理通过其抗氧化作用,防止了与对照心脏再灌注相关的所有受损模式,包括心脏功能、氧化应激和细胞凋亡。

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