Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing key Laboratory of pharmacology of Chinese Materia Region, Beijing 100091, PR China.
Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing key Laboratory of pharmacology of Chinese Materia Region, Beijing 100091, PR China.
Phytomedicine. 2022 Oct;105:154373. doi: 10.1016/j.phymed.2022.154373. Epub 2022 Aug 1.
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.
小胶质细胞在中风后可被激活为促炎（M1）表型和抗炎（M2）表型。小白菊内酯（PTL）对神经疾病具有抗炎和保护作用，但到目前为止，其在中风后的确切作用机制尚不清楚。本研究旨在确定 PTL 对中风后小胶质细胞极化的影响及其诱导小胶质细胞极化的作用靶点。
在局灶性短暂性脑缺血大鼠模型中进行氯化三苯基四氮唑（TTC）染色、苏木精-伊红（HE）染色和神经功能评估。采用脂多糖（LPS）暴露的人小胶质细胞进行体外实验。通过 RT-PCR 和免疫染色评估小胶质细胞极化。采用炎症细胞因子测定和 Western blot 检测体内和体外 PTL 介导的小胶质细胞极化的分子机制。
PTL 显著减轻了脑缺血大鼠的脑梗死和神经元凋亡，降低了炎症因子水平，减轻了神经功能缺损。PTL 治疗后，中风后 M1 巨噬细胞中小胶质细胞/巨噬细胞标志物的表达减少，M2 巨噬细胞中标志物的表达增加，诱导小胶质细胞从 M1 表型向 M2 表型转化。此外，PTL 显著降低了 RhoA/ROCK-NF-κB 通路的活性，并下调了戊酸（ROCK 激动剂）的作用。
PTL 通过调节 RhoA/ROCK 通路介导小胶质细胞极化，发挥神经炎症调节和对缺血性脑损伤的保护作用。
