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沙棘果肉油通过激活Akt/eNOS对大鼠心肌缺血再灌注损伤起到保护作用。

Seabuckthorn Pulp Oil Protects against Myocardial Ischemia-Reperfusion Injury in Rats through Activation of Akt/eNOS.

作者信息

Suchal Kapil, Bhatia Jagriti, Malik Salma, Malhotra Rajiv Kumar, Gamad Nanda, Goyal Sameer, Nag Tapas C, Arya Dharamvir S, Ojha Shreesh

机构信息

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

Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research Shirpur, India.

出版信息

Front Pharmacol. 2016 Jun 29;7:155. doi: 10.3389/fphar.2016.00155. eCollection 2016.

Abstract

Seabuckthorn (SBT) pulp oil obtained from the fruits of seabuckthorn [Hippophae rhamnoides L. (Elaeagnaceae)] has been used traditionally for its medicinal and nutritional properties. However, its role in ischemia-reperfusion (IR) injury of myocardium in rats has not been elucidated so far. The present study reports the cardioprotective effect of SBT pulp oil in IR-induced model of myocardial infarction in rats and underlying mechanism mediating activation of Akt/eNOS signaling pathway. Male albino Wistar rats were orally administered SBT pulp oil (5, 10, and 20 ml/kg/day) or saline for 30 days. On the day 31, ischemia was induced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. SBT pulp oil pretreatment at the dose of 20 ml/kg observed to stabilize cardiac function and myocardial antioxidants such as glutathione, superoxide dismutase, catalase, and inhibited lipid peroxidation evidenced by reduced malondialdehyde levels as compared to IR-control group. SBT pulp oil also improved hemodynamic and contractile function and decreased tumor necrosis factor and activities of myocyte injury marker enzymes; lactate dehydrogenase and creatine kinase-MB. Additionally, a remarkable rise in expression of pAkt-eNOS, Bcl-2 and decline in expression of IKKβ/NF-κB and Bax was observed in the myocardium. The histopathological and ultrastructural salvage of cardiomyocytes further supports the cardioprotective effect of SBT pulp oil. Based on findings, it can be concluded that SBT pulp oil protects against myocardial IR injury mediating favorable modulation of Akt-eNOS and IKKβ/NF-κB expression.

摘要

沙棘(SBT)果肉油取自沙棘[沙棘属鼠李科(胡颓子科)]果实,传统上因其药用和营养特性而被使用。然而,其在大鼠心肌缺血再灌注(IR)损伤中的作用迄今尚未阐明。本研究报告了SBT果肉油对大鼠IR诱导的心肌梗死模型的心脏保护作用以及介导Akt/eNOS信号通路激活的潜在机制。雄性白化Wistar大鼠口服给予SBT果肉油(5、10和20 ml/kg/天)或生理盐水,持续30天。在第31天,通过一次性结扎左冠状动脉前降支诱导缺血45分钟,随后再灌注60分钟。观察到20 ml/kg剂量的SBT果肉油预处理可稳定心脏功能和心肌抗氧化剂,如谷胱甘肽、超氧化物歧化酶、过氧化氢酶,并抑制脂质过氧化,与IR对照组相比,丙二醛水平降低证明了这一点。SBT果肉油还改善了血流动力学和收缩功能,降低了肿瘤坏死因子和心肌损伤标志物酶的活性;乳酸脱氢酶和肌酸激酶-MB。此外,在心肌中观察到pAkt-eNOS、Bcl-2表达显著升高,IKKβ/NF-κB和Bax表达下降。心肌细胞的组织病理学和超微结构挽救进一步支持了SBT果肉油的心脏保护作用。基于这些发现,可以得出结论,SBT果肉油可预防心肌IR损伤,介导Akt-eNOS和IKKβ/NF-κB表达的有利调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1151/4925700/db38b346c037/fphar-07-00155-g001.jpg

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