Isosteviol Sodium Protects Against Permanent Cerebral Ischemia Injury in Mice via Inhibition of NF-kappa B-Mediated Inflammatory and Apoptotic Responses
Isosteviol Sodium Protects Against Permanent Cerebral Ischemia Injury in Mice via Inhibition of NF-kappa B-Mediated Inflammatory and Apoptotic Responses
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异甜菊醇钠通过抑制 NF-kappa B 介导的炎症和细胞凋亡反应来预防小鼠永久性脑缺血损伤
DOI：
10.1016/j.jstrokecerebrovasdis.2017.06.023
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发表时间：
2017
影响因子：
2.5
通讯作者：
Tan Wen
中科院分区：
文献类型：
--
作者：
Zhang Hao;Sun Xiaoou;Xie Yanxiang;Zan Jie;Tan Wen
研究背景二骨维洛钠（STVNa）对大鼠缺血/再灌注（I/R）损伤具有神经保护作用。此外，再通治疗，包括溶栓治疗，有一些局限性。过度的炎症和细胞凋亡参与缺血性脑损伤的发病机制。活化B细胞的核因子κB轻链增强子（NF-κB）在这些过程中起关键作用，并与脑缺血有关。因此，我们研究STVNa对小鼠永久性脑缺血的潜在治疗作用及其机制。方法采用缝合法建立永久性大脑中动脉闭塞（pMCAO），然后静脉注射STVNa（7.5、15、30、45、60 mg/kg）。脑缺血后24小时检测神经行为缺损、梗死面积和组织学。采用实时定量聚合酶链反应（qPCR）检测NF-κ b相关基因的信使RNA （mRNA）表达。结果stvna （30 mg/kg）在pMCAO后24小时具有明显的神经保护作用，包括减少梗死面积和改善神经系统严重程度评分。免疫组化显示STVNa显著增加了恢复神经元的数量，减少了星形胶质细胞的数量。qPCR还显示，STVNa处理后，核因子κ b激酶抑制剂-α、核因子κ b激酶抑制剂-β、NF-κB、NF-κB抑制剂-α、肿瘤坏死因子-α、白细胞介素-1 β、bcl2相关X蛋白和caspase-3 mRNA表达量显著下调，而b细胞CLL/淋巴瘤2 mRNA表达量上调。结论STVNa可能通过与NF-κB信号通路的相互作用以及相关的炎症和凋亡反应，在脑缺血过程中发挥神经保护作用。
BackgroundIsosteviol sodium (STVNa) has been reported to have neuroprotective effects against ischemia/reperfusion (I/R) injury in rats. Furthermore, recanalization treatments, including thrombolytic therapy, have several limitations. Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic brain damage. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is critical to these processes and is associated with cerebral ischemia. Therefore, we studied the potential therapeutic effects and mechanisms of STVNa on permanent cerebral ischemia in mice.MethodsPermanent middle cerebral artery occlusion (pMCAO) was established via the suture method, followed by intravenous STVNa (7.5, 15, 30, 45, and 60 mg/kg). Neurobehavioral deficits, infarct volume, and histology were examined 24 hours after cerebral ischemia. In addition, the messenger RNA (mRNA) expression of NF-κB–related genes was detected using real-time quantitative polymerase chain reaction (qPCR).ResultsSTVNa (30 mg/kg) had significant neuroprotective effects 24 hours after pMCAO, including the reduction of the infarct volume and the improvement of the neurological severity score. Immunohistochemistry demonstrated that STVNa significantly increased the number of restored neurons and decreased the number of astrocytes. qPCR also demonstrated that the mRNA expression of inhibitor of nuclear factor kappa-B kinase-α, inhibitor of nuclear factor kappa-B kinase-β, NF-κB, inhibitor of NF-κB-α, tumor necrosis factor-α, interleukin-1 beta, Bcl2-associated X protein, and caspase-3 were significantly downregulated, whereas B-cell CLL/lymphoma 2 mRNA was upregulated with STVNa treatment compared with vehicle.ConclusionsThese findings demonstrate a neuroprotective role of STVNa during cerebral ischemia, which may result from interactions with the NF-κB signaling pathway and the associated inflammatory and apoptotic responses.