Resveratrol attenuates ischemic brain damage in the delayed phase after stroke and induces messenger RNA and protein express for angiogenic factors
Resveratrol attenuates ischemic brain damage in the delayed phase after stroke and induces messenger RNA and protein express for angiogenic factors
复制标题
白藜芦醇可减轻中风后延迟期的缺血性脑损伤，并诱导血管生成因子的信使 RNA 和蛋白质表达
DOI：
10.1016/j.jvs.2008.04.007
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发表时间：
2008-09-01
影响因子：
4.3
通讯作者：
Li, FanFan
中科院分区：
文献类型：
--
作者：
Dong, WenPeng;Li, NanLin;Li, FanFan
背景：最近有报道白藜芦醇预适应对脑缺血再灌注损伤有保护作用。然而，卒中后给予白藜芦醇是否有利于局灶性脑缺血损伤后的延迟期仍是个未知数。本研究探讨白藜芦醇油对小鼠局灶性脑缺血损伤后延迟期的作用及其可能的保护机制。方法：将小鼠按给药时间随机分为5组。对照组小鼠灌胃给予等量生理盐水(0.9%氯化钠)和20%羟丙基h-环糊精，造成大脑中动脉闭塞和再灌注损伤。各治疗组给予白藜芦醇(50 mg/kg/d，灌胃)至第7天。缺血组于大脑中动脉缺血前5min给予首剂，再灌注组于大脑中动脉再灌注前5min给予首剂，模型组于大脑中动脉再灌注后24小时给予首剂，第3天组于大脑中动脉再灌注后72小时给予首剂。再灌流7d后，用氯化三苯四氮唑染色和神经功能检查评价脑损伤程度。免疫组织化学染色检测微血管细胞数。用逆转录聚合酶链式反应和免疫印迹法检测白藜芦醇油基质金属蛋白酶-2(MMP2)和血管内皮生长因子(VEGF)基因表达的变化。结果：脑缺血再灌注组7d神经功能评分和脑梗塞体积均低于对照组(P<0.05)。免疫组织化学染色显示，缺血再灌注组小鼠皮质区微血管数量较对照组明显减少。缺血再灌注组缺血侧脑组织中MMP2和VEGFF蛋白水平显著升高(P<0.05)。结论：白藜芦醇灌胃给药对延迟期局灶性脑缺血损伤具有重要的神经保护作用。白藜芦醇通过诱导血管生成发挥神经保护作用，其机制可能与其升高的基质金属蛋白酶-2和血管内皮生长因子水平有关。
Background: It has been reported recently that resveratrol preconditioning can protect the brain from ischemia-reperfusion injury. However, it was nuclear whether resveratrol administration after stroke was beneficial to the delayed phases after focal cerebral ischemia injury. This study investigated the effects and possible protective mechanism of resveratrol oil the delayed phase after focal cerebral ischemia injury, in mice.Methods: Mice were randomly assigned to five groups according to the time of administration of resveratrol. Control group mice received a corresponding volume of saline solution (0.9% NaCl) containing 20% hydroxypropyl h-cyclodextrin by gavage and were exposed to middle cerebral artery (MCA) occlusion and reperfusion injury. The treatment groups received resveratrol (50 mg/kg/d, gavage) until day 7. Ischemia group mice received their first dose 5 minutes before MCA ischemia, reperfusion group mice received their first dose 5 minutes before MCA reperfusion,, group mice received their first dose 24 hours after MCA reperfusion, and third-day group mice received their first-day first dose at 72 hours after MCA reperfusion. Brain injury, was evaluated by triphenyltetrazolium chloride staining and neurologic examination 7 days after reperfusion. The microvascular cell number was examined with immunohistochemistry staining. Effect of resveratrol oil matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) gene expression was investigated with reverse transcriptase-polymerase chain reaction and Western blot.Results: The mean neurologic scores and infarct volumes of the ischemia and reperfusion groups were lower than that of the control group at 7 days after MCA reperfusion (P < .05). Immunohistochemistry staining showed significantly less reduction in the number of microvessels in the cortical area of mice of the ischemia and reperfusion groups compared with controls. The ischemic hemispheres of the ischemia and reperfusion groups showed significantly (P < .05) elevated levels of protein of MMP-2 and VEGF.Conclusions: Resveratrol administration by gavage provided an important neuroprotective effect oil focal cerebral ischemic injury in the delayed phase. The elevated MMP-2 and VEGF levels might be important ill the neuroprotective effect of resveratrol administration by inducing angiogenesis.