白藜芦醇通过抑制TNF-α表达保护大鼠脑缺血再灌注损伤
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(1.郑州人民医院神经内科,河南省郑州市 450003;2.郑州大学第一附属医院神经内科,河南省郑州市 450052)

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张莉峰,博士研究生,副主任医师,研究方向为脑血管病、癫痫、神经电生理,E-mail为bee9416@163.com。

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Resveratrol alleviates nerve injury after cerebral ischemia and reperfusion in mice by inhibiting the expression of TNF-α
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1.Department of Neurology, Zhengzhou People's Hospital, Zhengzhou, Henan 450003;2.the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052)

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    摘要:

    目的 探讨不同浓度白藜芦醇对缺血再灌注大鼠神经功能损伤及肿瘤坏死因子α(TNF-α)表达的影响。方法 将150只健康成年雄性SD大鼠随机分成5组:假手术组、模型组(I/R组)、小剂量白藜芦醇(2.5 mg/kg)组、中剂量白藜芦醇(5 mg/kg)组、大剂量白藜芦醇(10 mg/kg)组,每组30只。模型组和白藜芦醇组在制作脑缺血再灌注损伤模型20 min前分别给予生理盐水或不同浓度白藜芦醇腹腔注射,术后6 h、24 h、48 h、72 h、7天时间节点分别评定神经功能缺损评分。应用四氮唑红染色(TTC)脑组织后计算脑梗死病灶体积并比较5组的差异;分别应用免疫组织化学检测缺血脑组织周边区组织的TNF-α表达量并比较5组的差异。结果 (1)模型组大鼠在缺血再灌注后各时间点均有神经功能缺损,白藜芦醇可改善神经功能缺损,剂量越大,改善越明显。(2)白藜芦醇干预各组大鼠的脑梗死体积显著减少(P<0.05),呈显著剂量依赖性。(3)在各个时间点,各组大鼠缺血周边区脑组织的TNF-α阳性细胞数为:模型组>小剂量白藜芦醇组>中剂量白藜芦醇组>大剂量白藜芦醇组>假手术组(P<0.05)。结论 (1)缺血再灌注脑损伤过程中,白藜芦醇能有效的保护大鼠脑神经细胞,减少脑梗死体积,改善神经功能缺损评分,这一作用可能是通过抑制TNF-α表达来完成的。(2)白藜芦醇对脑缺血再灌注损伤的保护作用与剂量相关,并且呈现显著剂量依赖性。

    Abstract:

    Aim To explore the role and mechanism of different concentrations of resveratrol in the neurological function and the expression of tumor necrosis factor-α (TNF-α) of cerebrally injured rats with ischemia-reperfusion. Methods The 150 healthy adult male SD rats were randomly divided into 5 groups:sham operation group, model group, low dose resveratrol (2.5 mg/kg) group, middle dose resveratrol (5 mg/kg) group, high dose resveratrol (10 mg/kg) group, 30 rats for each group. Model group and resveratrol group were given with normal saline or different concentrations of resveratrol by intraperitoneal injection 20 minutes before the reperfusion. The nerve function defect scores were evaluated 6 hours, 24 hours, 48 hours, 72 hours, and 7 days of time after the operation. The cerebral infarction focus volume was calculated and the difference among the five groups was compared after TTC staining of brain tissues; the TNF-α was tested around the area of ischemia brain tissues by immunohistochemistry, and the differences was compared among the five groups. Results (1) Comparison of neurological deficit scores:the intervention of different concentrations of resveratrol has significantly improved the neurological deficit of rats, meanwhile, the higher the dose of resveratrol was, the more obvious the improvement of rats' neurological deficit has got, and it was in a dose-dependent manner. (2) Comparison of cerebral infarction focus volumes:the intervention of different concentrations of resveratrol has significantly reduced the cerebral infarction volumes of rats in different groups (P<0.05), and the higher the dose of resveratrol was, the larger the volume of reduced cerebral infarction was, and it was in a dose-dependent manner. (3) Comparison of immunohistochemistry of tissues surrounding the cerebral ischemia areas:at different hours, the numbers of TNF-α positive cells in the brain tissues surrounding the rats' cerebral ischemia area were:model group> low dose resveratrol group> middle dose resveratrol group> high dose resveratrol group> sham operation group (P<0.05), and the higher the dose of resveratrol was, the smaller the number of TNF-α positive cells were (P<0.05), which was in a dose-dependent manner. Conclusions (1) In the process of cerebral ischemia-reperfusion injury, resveratrol can reduce cerebral infarction volume and improve neurological deficit scores in a dose-dependent manner. It can also inhibit the expression of TNF-α through some kind of mechanism. (2) The protective effects of resveratrol on cerebral ischemia reperfusion injury was dose-related, and showed a significant dose-dependent manner.

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张莉峰,滕军放,袁学谦,朱太卿,张存玲.白藜芦醇通过抑制TNF-α表达保护大鼠脑缺血再灌注损伤[J].中国动脉硬化杂志,2017,25(1):32~36.

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  • 收稿日期:2016-03-18
  • 最后修改日期:2016-07-04
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  • 在线发布日期: 2017-02-08