Hypertonic saline mediates the NLRP3/IL-1β signaling axis in microglia to alleviate ischemic blood-brain barrier permeability by downregulating astrocyte-derived VEGF in rats.
Hypertonic saline mediates the NLRP3/IL-1β signaling axis in microglia to alleviate ischemic blood-brain barrier permeability by downregulating astrocyte-derived VEGF in rats.
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高渗盐水介导小胶质细胞中的NLRP3/IL-1β信号轴，通过下调大鼠星形胶质细胞衍生的VEGF来减轻缺血性血脑屏障通透性
DOI：
10.1111/cns.13427
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发表时间：
2020-10
影响因子：
5.5
通讯作者：
Zeng HK
中科院分区：
文献类型：
--
作者：
Wang QS;Ding HG;Chen SL;Liu XQ;Deng YY;Jiang WQ;Li Y;Huang LQ;Han YL;Wen MY;Wang MQ;Zeng HK
本研究旨在探讨高渗盐水(HS)的抗脑水肿作用是否与下调小胶质细胞源性结节样受体蛋白3(NLRP3)炎性小体介导的星形胶质细胞源性血管内皮生长因子(VEGF)，从而减轻脑缺血血脑屏障(BBB)通透性有关。测定脑梗塞体积和血脑屏障通透性。观察10%HS对大鼠局灶性脑缺血模型星形胶质细胞血管内皮生长因子蛋白表达的影响。检测星形胶质细胞NLRP3炎性小体、白介素1β蛋白表达及白介素1受体(IL1R1)/pNF-VEGFBp65/к信号通路的变化。HS可减轻星形胶质细胞血脑屏障通透性，缩小脑梗塞体积，下调星形胶质细胞血管内皮生长因子的表达。HS通过抑制小胶质细胞中NLRP3炎性小体的激活而下调IL-1β的表达，进而通过抑制IL-1к介导的星形胶质细胞中的NF-βBp65的磷酸化而下调VEGFR的表达。HS可减轻星形胶质细胞血脑屏障通透性，缩小脑梗塞体积，下调星形胶质细胞血管内皮生长因子的表达。HS通过抑制小胶质细胞中NLRP3炎性小体的激活而下调IL-1β的表达，进而通过抑制IL-1к介导的星形胶质细胞中的NF-βBp65的磷酸化而下调VEGFmRNA的表达。高渗盐水通过下调星形胶质细胞来源的血管内皮生长因子，抑制小胶质细胞中NLRP3炎症体的激活，从而减轻缺血血脑屏障的通透性。
The aim of this study was to explore whether the antibrain edema of hypertonic saline (HS) is associated with alleviating ischemic blood‐brain barrier (BBB) permeability by downregulating astrocyte‐derived vascular endothelial growth factor (VEGF), which is mediated by microglia‐derived NOD‐like receptor protein 3 (NLRP3) inflammasome. The infarct volume and BBB permeability were detected. The protein expression level of VEGF in astrocytes in a transient focal brain ischemia model of rats was evaluated after 10% HS treatment. Changes in the NLRP3 inflammasome, IL‐1β protein expression, and the interleukin‐1 receptor (IL1R1)/pNF‐кBp65/VEGF signaling pathway were determined in astrocytes. HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulates IL‐1β expression by inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulates VEGF expression by inhibiting the phosphorylation of NF‐кBp65 mediated by IL‐1β in astrocytes. HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulated IL‐1β expression via inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulated VEGF expression through inhibiting the phosphorylation of NF‐кBp65 mediated by IL‐1β in astrocytes. Hypertonic saline inhibits activation of NLRP3 inflammasome in microglia to alleviate ischemic blood‐brain barrier permeability by downregulating astrocyte‐derived VEGF.
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DOI：
10.1097/shk.0b013e3182894016
发表时间：
2013-04
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Banerjee A;Moore EE;McLaughlin NJ;Lee L;Jones WL;Johnson JL;Nydam TL;Silliman CC
通讯作者：
Silliman CC
影响因子：
5.6
作者：
Lee, Myoungsook;Sorn, Sungbin Richard;Kang, Inhae
通讯作者：
Kang, Inhae
影响因子：
15.9
作者：
Junger, WG;Hoyt, DB;Altman, A
通讯作者：
Altman, A
影响因子：
9.3
作者：
Huang LQ;Zhu GF;Deng YY;Jiang WQ;Fang M;Chen CB;Cao W;Wen MY;Han YL;Zeng HK
通讯作者：
Zeng HK
高渗盐水通过抑制星形胶质细胞中血管内皮生长因子及其受体 VEGFR2 的表达减轻实验诱导的脑水肿
影响因子：
2.4
作者：
Huang L;Cao W;Deng Y;Zhu G;Han Y;Zeng H
通讯作者：
Zeng H