Poncirin suppresses lipopolysaccharide (LPS)-induced microglial inflammation and ameliorates brain ischemic injury in experimental stroke in mice.
Poncirin suppresses lipopolysaccharide (LPS)-induced microglial inflammation and ameliorates brain ischemic injury in experimental stroke in mice.
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枳实苷可抑制脂多糖 (LPS) 诱导的小胶质细胞炎症，并改善小鼠实验性中风中的脑缺血性损伤。
DOI：
10.21037/atm-20-3470
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发表时间：
2020-11
影响因子：
--
通讯作者：
Cao X
中科院分区：
文献类型：
--
作者：
Yang LX;Chen FY;Yu HL;Liu PY;Bao XY;Xia SN;Gu Y;Xu Y;Cao X
研究背景越来越多的证据表明，小胶质细胞介导的炎症反应过度激活在缺血性脑卒中中起重要作用。Poncirin（Pon）对多种疾病具有抗痛觉过敏、抗神经过敏和抗肿瘤作用。然而，Pon在小胶质细胞活化中的作用及其机制尚未阐明。本研究旨在探讨Pon是否能抑制脂多糖（LPS）诱导的小胶质细胞炎症反应，并对实验性脑卒中小鼠脑缺血损伤具有保护作用。方法取1 ~ 2d龄C57 BL/6 J小鼠大脑皮质，分离培养原代小胶质细胞。用LPS刺激小鼠BV 2细胞和原代小胶质细胞，并使用实时PCR和酶联免疫吸附测定（ELISA）测量非细胞毒性浓度的Pon对LPS刺激的促炎因子的影响。Western印迹分析用于机制研究。在体内研究中，通过大脑中动脉闭塞（MCAO）使8周龄雄性C57 BL/6 J小鼠经受局灶性脑缺血。Pon（30 mg/kg，i.p.）或在建立MCAO模型后给予等体积的生理盐水，采用氯化三苯基四氮唑（TTC）染色法测定梗死体积。我们还评估了动物的行为，促炎细胞因子的表达和小胶质细胞活化在缺血半球。结果Pon可抑制LPS刺激的BV 2细胞和原代小胶质细胞释放一氧化氮（NO）、前列腺素E2（PGE 2）、白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α（TNF-α）。Pon的抑制作用与其对ERK 1/2、JNK和核因子κ B（NF-κB）信号通路的调节有关。在经历MCAO的小鼠中，Pon给药减小了病变大小并改善了神经功能缺损。Pon主要通过抑制缺血性脑卒中后小胶质细胞的活化来抑制炎性细胞因子的产生。结论Pon通过对小胶质细胞的抗炎作用发挥神经保护作用，有望成为治疗缺血性脑卒中的有效药物。
Background Based on accumulating evidence, excessive activation of microglia-mediated inflammatory responses plays an essential role in ischemic stroke. Poncirin (Pon) exerts anti-hyperalgesic, anti-osteoporotic and anti-tumor effects on various diseases. However, the roles of Pon in microglial activation and the underlying mechanism have not been elucidated. This study aimed to explore whether Pon inhibits lipopolysaccharide (LPS)-induced microglial neuroinflammation and protects against brain ischemic injury in experimental stroke in mice. Methods Primary microglia cells were prepared from the cerebral cortices of 1- to 2-day-old C57BL/6J mice. Murine BV2 cells and primary microglia were stimulated with LPS and the effects of a non-cytotoxic concentration of Pon on LPS-stimulated pro-inflammatory factors were measured using real-time PCR and enzyme-linked immunosorbent assays (ELISAs). Western blot analyses were used for mechanistic studies. In an in vivo study, 8-week-old male C57BL/6J mice were subjected to focal cerebral ischemia through middle cerebral artery occlusion (MCAO). Pon (30 mg/kg, i.p.) or the same volume of saline was administered after the MCAO model was established, and the infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. We also evaluated animal behaviours, the expression of pro-inflammatory cytokines and microglial activation in the ischemic hemisphere. Results Pon prevented the release of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha (TNF-α) in both BV2 cells and primary microglia stimulated with LPS. The inhibitory effects of Pon were associated with the regulation of the ERK1/2, JNK and nuclear factor kappa B (NF-κB) signaling pathways. In mice that underwent MCAO, Pon administration decreased the lesion size and improved neurological deficits. Furthermore, Pon attenuated the production of inflammatory cytokines mainly by restraining microglial activation after ischemic stroke. Conclusions Based on the findings from the present study, Pon provides neuroprotection through its anti-inflammatory effects on microglia and it may be a useful treatment for ischemic stroke.
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影响因子：
3.7
作者：
Chun, Kwang-Hoon;Jin, Hyun Chul;Hwang, Gwi Seo
通讯作者：
Hwang, Gwi Seo
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
5.6
作者：
Kang, Geum-Dan;Kim, Dong-Hyun
通讯作者：
Kim, Dong-Hyun
DOI：
10.1097/00004647-199802000-00008
发表时间：
1998-02-01
影响因子：
6.3
作者：
Loddick, SA;Turnbull, AV;Rothwell, NJ
通讯作者：
Rothwell, NJ
影响因子：
2.9
作者：
Hill, JK;Gunion-Rinker, L;Eckenstein, FP
通讯作者：
Eckenstein, FP