Protocatechuic Acid Suppresses Microglia Activation and Facilitates M1 to M2 Phenotype Switching in Intracerebral Hemorrhage Mice.
Protocatechuic Acid Suppresses Microglia Activation and Facilitates M1 to M2 Phenotype Switching in Intracerebral Hemorrhage Mice.
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DOI：
10.1016/j.jstrokecerebrovasdis.2021.105765
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
Zhiyu Xi;Can-xin Xu;Xiao Chen;Bao-feng Wang;Zhi-hong Zhong;Qingfang Sun;Yuhao Sun;L. Bian
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作者：
Zhiyu Xi;Can-xin Xu;Xiao Chen;Bao-feng Wang;Zhi-hong Zhong;Qingfang Sun;Yuhao Sun;L. Bian
小胶质细胞活化是脑出血后继发性损伤的关键过程，分为M1和M2两种表型。原儿茶酸(PCA)是一种酚酸，已被证明对脑出血有神经保护作用，但其细节尚不清楚。因此，本研究旨在观察PCA对小胶质细胞激活的影响，并探讨其可能的机制。材料和方法为了评价PCA对小胶质细胞激活的影响，建立了实验性脑出血小鼠模型，并用PCA进行治疗。脑出血后3d取脑切片进行免疫荧光染色。用氯化高铁血红素刺激BV2细胞激活，用Western Blot和qPCR分析M1和M2生物标志物。结果PCa治疗后3d，血肿周围活化的小胶质细胞聚集较少。此外，在氯化血红素处理的BV2细胞中，PCA在mRNA和蛋白水平上下调了M1的表达，促进了M2生物标志物的表达。PCA可抑制mTOR、S6K1和4E-BP1的磷酸化，加入mTOR激动剂后这种抑制作用消失。结论PCA通过抑制mTOR信号通路影响小胶质细胞的激活，从而改善M1/M2开关，减轻神经炎症。
ObjectivesMicroglia activation, a key process in secondary injury following intracerebral hemorrhage (ICH), is divided to M1 and M2 phenotype. Protocatechuic acid (PCA) is a phenolic acid been proved neuroprotection in ICH without understanding of details. Thus, this study aimed to observe the influence of PCA on microglia activation and explore underlying mechanisms.Materials and methodsTo assess PCA affected microglia activation in vivo, an experimental ICH mice model was established and then treated with PCA intraperitoneal injection. Immunofluorescence staining was performed in brain slices at day 3 post ICH. BV2 cells were stimulated with hemin for activation, then M1 and M2 biomarkers were analyzed using Western Blot and qPCR. At last, we detected the expression of mTOR and its downstream molecules to discuss possible mechanisms.ResultsAt day 3 post ICH, less activated microglia gathering around hematoma after PCA treatment. Furtherly, in hemin treated BV2 cells, PCA downregulated M1 and promoted M2 biomarkers expression in both mRNA and protein level. PCA inhibited the phosphorylation of mTOR, S6K1 and 4E-BP1, while the inhibition was disappeared after supplemented with mTOR activator.ConclusionsPCA impacted microglia activation by suppressing the mTOR signaling pathway, thereby improving M1/M2 switch and attenuated neuroinflammation.