Rifampicin Attenuated Global Cerebral Ischemia Injury via Activating the Nuclear Factor Erythroid 2-Related Factor Pathway.
Rifampicin Attenuated Global Cerebral Ischemia Injury via Activating the Nuclear Factor Erythroid 2-Related Factor Pathway.
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利福平通过激活核因子红细胞 2 相关因子途径减轻全脑缺血损伤
DOI：
10.3389/fncel.2016.00273
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发表时间：
2016
影响因子：
5.3
通讯作者：
Cheng O
中科院分区：
文献类型：
--
作者：
Chen B;Cao H;Chen L;Yang X;Tian X;Li R;Cheng O
背景：近年来研究发现利福平对神经退行性疾病具有神经保护作用。然而，确切的作用机制仍不清楚。核因子红细胞2相关因子2 （Nrf2）被认为是神经保护的潜在靶点。在这项研究中，我们研究了利福平是否在全脑缺血（GCI）后表现出Nrf2途径介导的有益作用。方法：将大鼠随机分为4组，包括假手术组和3组全脑缺血再灌注治疗组[对照组、利福平组、利福平加brusatol （Nrf2抑制剂）]。大鼠双侧颈总动脉闭塞致短暂性GCI 20 min，全身低血压。神经行为学检测采用Morris水迷宫法，病理改变采用HE和TUNEL染色。Western blotting检测海马组织中Nrf2、血红素加氧酶-1 （HO-1）、环氧合酶-2 （COX-2）蛋白的表达。采用免疫荧光染色法测定Nrf2的分布。结果：利福平治疗组大鼠空间学习能力较对照组明显提高，与病理变化一致。此外，与对照组相比，利福平显著升高Nrf2、Nrf2下游抗氧化蛋白HO-1的核表达，同时下调缺血再灌注后第3天海马组织COX-2的表达。有趣的是，利福平的效应通过预处理brusatol（一种特异性Nrf2激活抑制剂）而被消除。结论：利福平对全局性脑缺血具有神经保护作用，其机制可能与激活Nrf2通路有关。
Background: Recent studies have found that rifampicin has neuroprotective properties in neurodegenerative diseases. However, the exact mechanisms of action remain unclear. The nuclear factor erythroid 2-related factor 2 (Nrf2) has been considered a potential target for neuroprotection. In this study, we examined whether rifampicin exhibits beneficial effects mediated by the Nrf2 pathway after global cerebral ischemia (GCI). Methods: Rats were randomly assigned to four groups that included a sham group and three treatment groups with global ischemia-reperfusion [control, rifampicin, and rifampicin plus brusatol (an inhibitor of Nrf2)]. Rats were subjected to transient GCI induced by bilateral common carotid artery occlusion for 20 min with systemic hypotension by blood withdrawal. The Morris water maze test was performed for neurobehavioral testing, whereas the pathological changes were investigated using HE and TUNEL staining. The protein expression of Nrf2, hemeoxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) in the hippocampus were analyzed by Western blotting. The immunofluorescence staining was used to determine the distribution of Nrf2. Results: Rifampicin treatment significantly improved spatial learning ability compared with the control group, which was consistent with the pathological changes. In addition, rifampicin significantly elevated the nuclear expression of Nrf2, Nrf2 downstream anti-oxidant protein, HO-1 compared with the control group, and it simultaneously downregulated the expression of COX-2 in the hippocampus on day 3 after ischemia-reperfusion. Interestingly, the forenamed effects of rifampicin were abolished by pretreatment with brusatol, a specific inhibitor of Nrf2 activation. Conclusions: Rifampicin exerts neuroprotective effects against global cerebral ischemia, which may be attributed to activation of the Nrf2 pathway.
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黄芩苷通过减少海马细胞凋亡提高整体缺血/再灌注大鼠的空间学习能力
影响因子：
2.9
作者：
Cheng, Oumei;Li, Zhenhua;Cheng, Ke
通讯作者：
Cheng, Ke
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8.3
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影响因子：
6.6
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Mo, Chunfen;Wang, Ling;Xiao, Hengyi
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Xiao, Hengyi
影响因子：
4.6
作者：
Ding Y;Chen M;Wang M;Wang M;Zhang T;Park J;Zhu Y;Guo C;Jia Y;Li Y;Wen A
通讯作者：
Wen A
影响因子：
8.3
作者：
PULSINELLI, WA;BRIERLEY, JB
通讯作者：
BRIERLEY, JB