Paeoniflorin improves functional recovery through repressing neuroinflammation and facilitating neurogenesis in rat stroke model.
Paeoniflorin improves functional recovery through repressing neuroinflammation and facilitating neurogenesis in rat stroke model.
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作者：
Tang H;Wu L;Chen X;Li H;Huang B;Huang Z;Zheng Y;Zhu L;Geng W
小胶质细胞、神经元和血管细胞构成了一个动态的功能神经血管单位，在缺血性卒中后的功能恢复中起着至关重要的作用。芍药苷是赤芍的主要活性成分，已被证实对脑缺血损伤具有神经保护作用。然而，芍药苷对脑缺血后神经血管单位的调节作用机制尚不清楚。本研究采用成年雄性大鼠大脑中动脉短暂性闭塞(TMCAO)模型，给予白芍药苷治疗，观察其功能行为测试(足背痛试验和改良神经功能评分，mNSS)、小胶质细胞活化、神经发生和血管生成。目前的研究表明，在卒中大鼠模型中，通过足部错误试验和mNSS所显示的空间学习能力的增强，芍药苷治疗显示出感觉运动功能的恢复。芍药苷治疗可抑制小胶质细胞的增殖，导致促炎细胞因子IL-1β、IL-6和肿瘤坏死因子-α水平显著降低。与对照组相比，用药组促进了血管内皮细胞标志物von Willebrand因子和神经母细胞标志物双皮质醇的表达，提示芍药苷参与了卒中模型大鼠的神经发生和血管生成。从机制上，我们证实了芍药苷抑制了JNK和NF-κB信号的激活。以上结果表明，白芍总苷具有抑制大鼠卒中模型神经炎症、促进神经再生的作用，有望成为治疗缺血性卒中的潜在药物。
Microglia, neuron, and vascular cells constitute a dynamic functional neurovascular unit, which exerts the crucial role in functional recovery after ischemic stroke. Paeoniflorin, the principal active component of Paeoniae Radix, has been verified to exhibit neuroprotective roles in cerebralischemic injury. However, the mechanisms underlying the regulatory function of Paeoniflorin on neurovascular unit after cerebral ischemia are still unclear. In this study, adult male rats were treated with Paeoniflorin following transient middle cerebral artery occlusion (tMCAO), and then the functional behavioral tests (Foot-fault test and modified improved neurological function score, mNSS), microglial activation, neurogenesis and vasculogenesis were assessed. The current study showed that Paeoniflorin treatment exhibited a sensorimotor functional recovery as suggested via the Foot-fault test and the enhancement of spatial learning as suggested by the mNSS in rat stroke model. Paeoniflorin treatment repressed microglial cell proliferation and thus resulted in a significant decrease in proinflammatory cytokines IL-1β, IL-6 and TNF-α. Compared with control, Paeoniflorin administration facilitated von Willebrand factor (an endothelia cell marker) and doublecortin (a neuroblasts marker) expression, indicating that Paeoniflorin contributed to neurogenesis and vasculogenesis in rat stroke model. Mechanistically, we verified that Paeoniflorin repressed JNK and NF-κB signaling activation. These results demonstrate that Paeoniflorin represses neuroinflammation and facilitates neurogenesis in rat stroke model and might be a potential drug for the therapy of ischemic stroke.
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DOI：
10.1016/j.pnpbp.2016.07.003
发表时间：
2017-10-03
影响因子：
5.6
作者：
Anttila, Jenni E.;Whitaker, Keith W.;Wires, Emily S.;Harvey, Brandon K.;Airavaara, Mikko
通讯作者：
Airavaara, Mikko
芍药苷抑制内毒素处理的人单核细胞中细胞间粘附分子-1 (ICAM-1) 的表达
影响因子：
7.3
作者：
Jin, Lei;Zhang, Li-Min;Feng, Linyin
通讯作者：
Feng, Linyin
影响因子：
2.9
作者：
Liu, Jing;Jin, Dao-Zhong;Zhu, Xing-Zu
通讯作者：
Zhu, Xing-Zu
影响因子：
168.9
作者：
Emberson, Jonathan;Lees, Kennedy R.;Lyden, Patrick;Blackwell, Lisa;Albers, Gregory;Bluhmki, Erich;Brott, Thomas;Cohen, Geoff;Davis, Stephen;Donnan, Geoffrey;Grotta, James;Howard, George;Kaste, Markku;Koga, Masatoshi;von Kummer, Ruediger;Lansberg, Maarten;Lindley, Richard I.;Murray, Gordon;Olivot, Jean Marc;Parsons, Mark;Tilley, Barbara;Toni, Danilo;Toyoda, Kazunori;Wahlgren, Nils;Wardlaw, Joanna;Whiteley, William;del Zoppo, Gregory J.;Baigent, Colin;Sandercock, Peter;Hacke, Werner
通讯作者：
Hacke, Werner
DOI：
10.1016/s0140-6736(17)32152-9
发表时间：
2017-09-16
期刊：
Lancet (London, England)
影响因子：
--
作者：
GBD 2016 Causes of Death Collaborators
通讯作者：
GBD 2016 Causes of Death Collaborators