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环氧二十碳三烯酸通过抑制炎症因子和泛连接蛋白-1改善脑缺血再灌注损伤。

Epoxyeicosatrienoic acid ameliorates cerebral ischemia-reperfusion injury by inhibiting inflammatory factors and pannexin-1.

作者信息

Liu Zhigang, Liu Yongfang, Zhou Haixiao, Fu Xiangyun, Hu Gang

机构信息

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Department of Plastic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):2179-2184. doi: 10.3892/mmr.2017.6831. Epub 2017 Jun 21.

DOI:10.3892/mmr.2017.6831
PMID:28656267
Abstract

Epoxyeicosatrienoic acid (EET) has wide applications due to the unique biological effects of anti‑hyperlipidemia, inhibition of platelet aggregation, anti‑inflammation, anti‑cancer, anti‑lipid oxidation and the promotion of brain tissue development. The present study investigated whether EET ameliorates cerebral ischemia‑reperfusion injury (CIRI) by inhibiting inflammatory factors and pannexin. Specific pathogen‑free 7‑week‑old male Sprague‑Dawley rats were randomly divided into three groups: Sham, CIRI and EET. Neurological deficit scores, cerebral infarct volume and cerebral edema were assessed in CIRI rats. Enzyme‑linked immunosorbent assays were performed to detect tumor necrosis factor‑α, interleukin‑6, nuclear factor‑κB and inducible nitric oxide synthase (iNOS) levels, and western blot analysis was performed also used to assess cleaved caspase‑3, phospholipase A2 (PLA2), cyclooxygenase‑2 and prostaglandin E2 (PGE2) protein expression levels. EET ameliorated cerebral injury and CIRI‑induced cleaved caspase‑3 protein expression levels in rats. EET additionally suppressed CIRI‑induced inflammation reactions and iNOS protein expression in rats. Furthermore, the protein expression levels of PLA2, PGE2 and pannexin‑1 in CIRI rats were inhibited by treatment with EET. These results indicated that EET reduces CIRI by inhibiting inflammation and levels of cleaved caspase‑3, PLA2, PGE2 and pannexin-1.

摘要

环氧二十碳三烯酸(EET)因其具有抗高血脂、抑制血小板聚集、抗炎、抗癌、抗脂质氧化以及促进脑组织发育等独特生物学效应而具有广泛应用。本研究调查了EET是否通过抑制炎症因子和泛连接蛋白来改善脑缺血再灌注损伤(CIRI)。将7周龄的无特定病原体雄性Sprague-Dawley大鼠随机分为三组:假手术组、CIRI组和EET组。评估CIRI大鼠的神经功能缺损评分、脑梗死体积和脑水肿。采用酶联免疫吸附测定法检测肿瘤坏死因子-α、白细胞介素-6、核因子-κB和诱导型一氧化氮合酶(iNOS)水平,并进行蛋白质印迹分析以评估裂解的半胱天冬酶-3、磷脂酶A2(PLA2)、环氧化酶-2和前列腺素E2(PGE2)的蛋白表达水平。EET改善了大鼠的脑损伤以及CIRI诱导的裂解的半胱天冬酶-3蛋白表达水平。EET还抑制了CIRI诱导的大鼠炎症反应和iNOS蛋白表达。此外,EET处理可抑制CIRI大鼠中PLA2、PGE2和泛连接蛋白-1的蛋白表达水平。这些结果表明,EET通过抑制炎症以及裂解的半胱天冬酶-3、PLA2、PGE2和泛连接蛋白-1的水平来减轻CIRI。

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