目的：观察抗坏血酸（ascorbic acid,AA）对脑出血（intracerebral hemorrhage,ICH）大鼠氧化应激与血脑屏障（blood-brain barrier,BBB）的作用,以及对ICH大鼠脑积水（post-hemorrhagic hydrocephalus,PHH）形成的影响。方法：通过自体血颅内注射建立ICH大鼠模型。观察AA对ICH大鼠PHH情况的影响,观察AA对ICH大鼠神经损伤情况的影响,检测氧化应激相关标志物的表达情况,检测BBB相关标志蛋白的表达情况。结果：相较于ICH组,ICH-AA组大鼠脑室体积更小,脑组织损伤程度更轻,神经元损伤得到缓解,脑含水量更低,神经功能评分（mNSS）更低,诱导型氧化氮合酶（inducible nitric oxide synthase,iNOS）和丙二醛（malondialdehyde,MDA）表达减少,超氧化物歧化酶（superoxide dismutase,SOD）表达增加,钠依赖性维生素C转运体2（sodium-dependent vitamin C transporter 2,SVCT2）表达上调,基质金属蛋白酶(matrix metallopeptidase,MMP)-2表达减少,闭合蛋白（occludin）、密封蛋白酶5（claudin-5）和紧密连接蛋白1（zonula occludens-1,ZO-1）表达增加。相较于PHH组,PHH-AA组大鼠脑室体积略有缩小,脑组织损伤程度基本一致,神经元损伤没有缓解,但脑含水量有所降低,神经功能评分（mNSS）得到改善,iNOS和MDA表达减少,SOD表达增加,SVCT2表达上调,MMP-2表达减少,occludin、claudin-5和ZO-1表达略有增加。结论：AA能抑制ICH大鼠氧化应激的程度并保护BBB,缓解PHH的形成,并在ICH早期起到神经保护作用;而在PHH形成后,AA仅能部分抑制氧化应激的程度,但对已经损伤的BBB没有修复作用,不能治疗PHH,但能起到神经保护作用。
Abstract
Objective To observe the effects of ascorbic acid (AA) on oxidative stress and blood-brain barrier (BBB) in rats with intracerebral hemorrhage (ICH), and on post-hemorrhagic hydrocephalus (PHH) formation in rats with ICH. Methods A rat model of PHH after ICH was developed through autologous blood infusion. To observe the effect of AA on the PHH condition of ICH rats, to observe the effect of AA on the nerve damage condition of ICH rats, to detect the expression of oxidative stress-related markers, and to detect the expression of BBB-related marker proteins. Results Compared with the ICH group, rats in the ICH-AA group had a smaller ventricular volume, a lesser degree of brain tissue damage, alleviated neuronal damage, lower brain water content, lower neurological function scores mNSS, decreased iNOS and MDA expression, increased SOD expression, up-regulated SVCT2 expression, decreased MMP-2 expression, and increased occludin, claudin-5, and ZO-1 expression. Compared with the PHH group, the ventricular volume of rats in the PHH-AA group was slightly reduced, the degree of brain tissue damage was basically the same, neuronal damage was not alleviated, but the brain water content was reduced, neurological function scores of mNSS were improved, iNOS and MDA expression was reduced, SOD expression was increased, SVCT2 expression was up-regulated, MMP-2 expression was reduced, and the expression of occludin, claudin-5, and ZO-1 expression was slightly increased. Conclusion AA inhibited the degree of oxidative stress and protected the BBB in ICH rats, alleviated the formation of PHH, and played a neuroprotective role in the early stage of ICH; whereas, after the formation of PHH, AA only partially inhibited the degree of oxidative stress but did not have any reparative effect on the BBB that had been damaged, and could not treat PHH, but could play a neuroprotective role.
关键词
抗坏血酸 /
氧化应激 /
血脑屏障 /
脑积水 /
脑出血 /
神经保护作用
Key words
ascorbic acid /
oxidative stress /
blood brain barrier /
hydrocephalus /
intracerebral hemorrhage /
neuroprotective
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基金
湖南省卫生健康委科研计划项目（202204040024）; 国家自然科学基金委员会面上项目（82171347）; 湖南省自然科学基金面上项目（2022JJ30971）
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