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| 异氟醚后处理对局灶性脑缺血-再灌注大鼠海马神经损伤的影响 |
| Effect of isoflurane post-conditioning on hippocampus neurons with cerebral ischemic reperfusion injury in rats |
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| DOI：10.12089/jca.2019.01.015 |
| 中文关键词: 异氟醚 Wnt/β- catenin 信号通路 局灶性脑缺血-再灌注损伤 神经元 |
| 英文关键词: Isoflurane postcondition Wnt/β-catenin signaling pathway Cerebral ischemia- reperfusion injury Neuron |
| 基金项目:国家自然科学基金（81860249,81360203） |
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| 中文摘要: |
目的 观察异氟醚后处理是否通过Wnt/β-catenin信号通路减轻局灶性脑缺血-再灌注损伤（cerebral ischemia-reperfusion injury，CIRI）大鼠海马神经元损伤。
方法 60只雄性SD大鼠随机分为五组，每组12只。采用大脑中动脉栓塞法(middle cerebral artery occlusion, MCAO)缺血90 min、再灌注24 h制备大鼠局灶性CIRI模型：假手术组（S组）、模型组（M组）、异氟醚后处理+模型组（MI组）、Wnt/β-catenin拮抗剂Dicckkopf-1（DKK-1）+异氟醚后处理+模型组（MDI组）、DKK-1+模型组（MD组）。S组仅分离暴露一侧颈内动脉，不插入线栓。MI和MDI组于再灌注即刻行1.5%异氟醚后处理60 min。MDI组和MD组于建立模型前30 min行侧脑室注射DKK-1（5 μg/kg）。所有模型组大鼠在再灌注24 h后，采用Longa评分法进行神经行为学评分，HE染色观察神经细胞形态学变化，免疫组化检测大鼠海马CA1区β-catenin的表达，Tunel荧光检测大鼠海马CA1区神经细胞凋亡情况，Western Blot检测Bcl-2、Bax、β-catenin及GSK-3β蛋白含量，并计算Bcl-2/Bax比值。
结果 与S组比较，M组大鼠神经行为学评分、神经细胞损伤及凋亡数目、Bax以及GSK-3β蛋白含量均明显增加（P<0.05），而β-catenin蛋白含量及Bcl-2/Bax 比值明显减少(P<0.05)。与M组比较，MI组大鼠神经行为学评分、神经细胞损伤及凋亡数目以及 Bax 蛋白含量明显减少(P<0.05)，Bcl-2和β-catenin蛋白含量以及Bcl-2/Bax比值明显增加(P<0.05)。与MI 组比较，MDI 组大鼠神经行为学评分、神经细胞损伤及凋亡数目及Bax、GSK-3β蛋白含量明显增加(P<0.05)，而Bcl-2、β-catenin蛋白含量及Bcl-2/Bax比值明显减小(P<0.05)。
结论 异氟醚后处理可能是通过影响Wnt/β-catenin信号通路，调控Bcl-2及Bax的表达，从而减轻局灶性CIRI大鼠海马神经元损伤。 |
| 英文摘要: |
Ojective To investigate whether Wnt/β-catenin signaling pathway mediating the neuroprotection of isoflurane post-conditioning in hippocampal neurons damage induced by ischemia/reperfusion injury in rats.
Methods According to the randomized principle, 60 male Sprague-Dawley rats were randomly divided into five groups (12 rats in each group): sham group (group S), model group (group M), ISO+model group (group MI), ISO+model+DKK-1 group (group MDI) and model+DKK-1 group (group MD). A rat model of middle cerebral artery occlusion (MCAO) was established with 90 min ischemia followed by 24 h reperfusion. Group S was only exposed to one side of the internal carotid artery without fishing line. Isoflurane post-conditioning groups (group MI, MDI) were immediately treated with 1.5% isoflurane for 60 min at the onset of reperfusion. DKK-1 (5 μg/kg) was injected intracerebroventricularly 30 min before the model established in group MDI and group MD. After reperfusion for 24 h, Longa score method was used for neurological deficit score. HE staining and Tunel fluorescence was employed to observe the morphological changes of neurons. Immunohistochemistry and Western Blot were applied to detect the expression of target protein in CA1 region.
Results Compared with group S, the neurobehavioral score, the number of apoptosis and the expression of Bax and GSK-3β protein in group M all increased (P < 0.05), while the expression of β-catenin and Bcl-2/Bax ratio decreased (P < 0.05); Compared with group M, the neurobehavioral score, the number of apoptosis and the expression of Bax protein were significantly decreased (P < 0.05), while the expression of Bcl-2,β-catenin protein and the Bcl-2/Bax ratio were significantly increased (P < 0.05) in group MI. Compared with group MI, the neurobehavioral score, the number of apoptosis，Bax and GSK-3β protein in group MDI were significantly increased (P < 0.05), while the Bcl-2, β-catenin protein expression, and Bcl-2/Bax ratio were significantly decreased (P < 0.05).
Conclusion Isoflurane post-conditioning may protect the hippocampus neurons against cerebral ischemic reperfusion-induced damage via the way that the Wnt/β-catenin signaling pathway regulates the expression levels of Bcl-2 and Bax proteins in rats. |
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