Parthenolide modulates cerebral ischemia-induced microglial polarization and alleviates neuroinflammatory injury via the RhoA/ROCK pathway
Parthenolide modulates cerebral ischemia-induced microglial polarization and alleviates neuroinflammatory injury via the RhoA/ROCK pathway
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小白菊内酯通过 RhoA/ROCK 通路调节脑缺血诱导的小胶质细胞极化并减轻神经炎症损伤
DOI：
10.1016/j.phymed.2022.154373
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发表时间：
2022
期刊：
影响因子：
7.9
通讯作者：
Jianxun Liu
中科院分区：
文献类型：
--
作者：
Yehao Zhang;Lan Miao;Qing Peng;Xiaodi Fan;Wenting Song;Bin Yang;Peng Zhang;Guangyu Liu;Jianxun Liu
脑卒中后小胶质细胞可被激活为促炎（M1）表型和抗炎（M2）表型。Parthenolide （PTL）对神经系统疾病具有抗炎和保护作用，但到目前为止，中风后这些过程的确切机制尚不清楚。本研究的目的是确定PTL对脑卒中后小胶质细胞极化的影响及其诱导小胶质细胞极化的靶点。三苯四唑氯（TTC）染色、苏木精-伊红（HE）染色及神经学评价均用于局灶性短暂性脑缺血大鼠模型。体外实验采用脂多糖（LPS）作用的人小胶质细胞。采用RT-PCR和免疫染色检测小胶质细胞极化情况。采用炎症细胞因子检测和western blotting研究ptl介导的小胶质细胞极化在体内和体外的分子机制。PTL可显著减少脑缺血大鼠脑梗死和神经元凋亡，降低炎症因子水平，减轻神经功能缺损。PTL可降低脑卒中后M1巨噬细胞中小胶质/巨噬细胞标记物的表达，增加M2巨噬细胞中小胶质/巨噬细胞标记物的表达，诱导小胶质细胞由M1表型向M2表型转化。此外，PTL显著降低RhoA/ROCK- nf -κB通路活性，下调戊酸（ROCK激动剂）的作用。PTL已被证明通过RhoA/ROCK通路调节小胶质细胞极化，介导神经炎症并保护缺血性脑损伤。
Microglia can be activated as proinflammatory (M1) phenotypes and anti-inflammatory (M2) phenotypes after stroke. Parthenolide (PTL) has anti-inflammatory and protective effects on neurological diseases, but until now, the exact mechanisms of these processes after stroke have been unclear. The purpose of this study was to determine the effect of PTL on microglial polarization after stroke and its target for inducing microglial polarization.Triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and neurological evaluation were performed in a focal transient cerebral ischemia rat model. The human microglia exposed to lipopolysaccharide (LPS) was used for in vitro experiments. Microglial polarization was assessed by RT-PCR and immunostaining. Inflammatory cytokine assays and western blotting were used to investigate the molecular mechanisms underlying PTL-mediated microglial polarization in vivo and in vitro.PTL significantly reduced cerebral infarction and neuronal apoptosis in rats with cerebral ischemia, reduced the level of inflammatory factors and alleviated neurological deficits. PTL treatment decreased the expression of microglia/macrophage markers in M1 macrophages and increased the expression of microglia/macrophage markers in M2 macrophages after stroke, which induced the transformation of microglia cells from the M1 phenotype to the M2 phenotype. Furthermore, PTL significantly reduced RhoA/ROCK-NF-κB pathway activity and downregulated the effects of pentanoic acid (ROCK agonist).PTL has been shown to mediate neuroinflammation and protect against ischemic brain injury by regulating microglial polarization via the RhoA/ROCK pathway.