天麻素经p38 MAPK通路对M2型小胶质细胞极化的影响

doi:10.16098/j.issn.0529-1356.2024.06.002

解剖学报 ›› 2024, Vol. 55 ›› Issue (6): 657-666.doi: 10.16098/j.issn.0529-1356.2024.06.002

天麻素经p38 MAPK通路对M2型小胶质细胞极化的影响

赵永强^{1 ,2} 李顺达¹ 陈澍雨³ 杨雪珂⁴ 袁云^1*

1. 昆明医科大学基础医学院人体解剖学与组织学胚胎学系，昆明 650500; 2. 山东省庆云县疾病预防控制中心，山东庆云 253700; 3. 江西省妇幼保健院辅助生殖中心，南昌 330006; 4. 华中科技大学同济医学院附属武汉儿童医院，武汉 430015)

收稿日期:2023-09-08 修回日期:2023-11-02 出版日期:2024-12-06 发布日期:2024-12-06
通讯作者: 袁云 E-mail:yunyuankm@126.com
基金资助:
天麻素对新生大鼠缺血缺氧后Notch信号通路及Sirt3的影响及其调控机制的研究

Effect of gastrodin on M2 type polarization in activated microglia via p38 MAPK signaling

ZHAO Yong-qiang^1,2 LI Shun-da¹ CHEN Shu-yu³ YANG Xue-ke⁴ YUAN Yun^1*

1.Department of Human Anatomy，Histology and Embryology，School of Basic Medicine，Kunming Medical University, Kunming 650500,China;2.Shangdong Qingyun County Center for Disease Control and Prevention, Shandong Qingyun 253700, China;3. Department of Human Assisted Reproduction Center，Women and Children Health Care Hospital of Jiangxi Province, Nanchang 330006,China; 4.Wuhan Children’s Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan 430015, China)

Received:2023-09-08 Revised:2023-11-02 Online:2024-12-06 Published:2024-12-06
Contact: YUAN Yun E-mail:yunyuankm@126.com

摘要/Abstract

摘要：

目的探讨天麻素（GAS）对氧糖剥夺（OGD）作用下M2型小胶质细胞极化的影响及抑制p38 MAPK对小胶质细胞极化状态的影响。方法将BV2小胶质细胞分为对照组（Ctrl）、p38 MAPK 抑制剂SB203580组（I）、氧糖剥夺组（OGD）、氧糖剥夺+SB203580组（OGD+I）、天麻素干预组（G+OGD）、天麻素干预+SB203580组（G+OGD+I）。免疫荧光染色和Western blotting检测p38 MAPK、磷酸化p38 MAPK（p-p38 MAPK）和M2型标记物精氨酸酶1 （Arg-1）和几丁质酶样蛋白1/2（YM1/2）的表达。结果免疫荧光结果显示，天麻素干预可降低OGD诱导的BV2小胶质细胞p-p38 MAPK的荧光表达，增强Arg1、YM1/2荧光表达。各组p38 MAPK的荧光表达水平差异无统计学意义（n=3，P>0.05）。加入SB203580后，pp38 MAPK的荧光表达进一步降低，Arg-1、YM1/2的荧光表达进一步升高，与G+OGD组相比差异均有统计学意义（ n=3，P<0.05）。各组间p38 MAPK的荧光表达差异无显著性（ n=3，P >0.05）。Western blotting结果显示，OGD后p-p38 MAPK、Arg-1、YM1/2蛋白表达升高，与对照组相比差异有显著性（ n=3，P<0.05）；天麻素干预后，p-p38 MAPK蛋白表达明显降低，Arg-1、YM1/2蛋白表达显著增加，与OGD组相比差异均有显著性（ n=3，P<0.05）。加入SB203580后，p-p38 MAPK蛋白表达进一步降低，Arg-1、YM1/2蛋白表达进一步升高，与G+OGD组相比差异均有显著性（ n=3，P<0.05）。此外，各组间p38 MAPK蛋白表达差异无统计学意义（n=3，P>0.05）。结论天麻素可能通过抑制p38 MAPK活化促进BV2小胶质细胞向M2型极化，减轻炎症反应，从而发挥保护作用。

关键词: 天麻素, 氧糖剥夺, 极化, p38丝裂原活化蛋白激酶, 免疫印迹法, BV2小胶质细胞

Abstract:

Objective To explore the effect of gastrodin（GAS）on the polarization of M2 microglia under oxygen and glucose deprivation（OGD）and the effect of p38 MAPK inhibition on the polarization status of microglia. Methods BV2 microglia was divided into the control group（Ctrl），p38 MAPK inhibitor SB203580 group（I），OGD group (OGD)，OGD+I group，gastrodin treatment group（G+OGD），and G+OGD+I group. The expressions of p38 MAPK，phosphorylated p38 MAPK（p-p38 MAPK）, M2 microglia marker arginase-1 (Arg-1) and chitinase like protein 1/2（YM1/2）were detected by immunofluorescent staining and Western blotting. Results Immunofluorescent staining results showed that the pretreatment with gastrodin reduced the fluorescence expression of p-p38 MAPK in OGD induced BV2 microglia, enhanced the fluorescence expressions of Arg-1 and YM1/2. After pretreatment with SB203580，the fluorescence expressions of p-p38 MAPK further decreased，the fluorescence expressions of Arg1 and YM1/2 further increased，both were significantly different from the G+OGD group （ n=3，P<0.05）. The fluorescence expressions of p38 MAPK in each group was not statistically significant（ n=3，P>0.05）. Western blotting results showed that the protein expressions of p-p38 MAPK, Arg-1 and YM1/2 in the OGD group enhanced，compared with that in the control group（ n=3，P<0.05）. After the pretreatment with gastrodin，the protein expression of p-p38 MAPK was reduced significantly，the protein expressions of Arg-1 and YM1/2 was enhanced obviously，both were significantly different from the OGD group （ n=3，P<0.05）. After pretreatment with SB203580，the protein expressions of p-p38 MAPK was further reduced，the protein expression of Arg-1 and YM1/2 were further enhanced，both were significantly different from the G+OGD group（ n=3，P<0.05）. In addition，there was no significant change in p38 MAPK protein expression among groups （ n=3，P>0.05）. Conclusion Gastrodin inhibits p38 MAPK signaling activation to promote BV2 microglial polarization towards the M2 phenotype，reducing inflammatory responses and exerting a protective effect.

Key words: Gastrodin, Oxygen and glucose deprivation, Polarization, p38 mitogen-activated protein kinase, Western blotting, BV2 microglia

中图分类号:

R361

赵永强李顺达陈澍雨杨雪珂袁云 . 天麻素经p38 MAPK通路对M2型小胶质细胞极化的影响[J]. 解剖学报, 2024, 55(6): 657-666.

ZHAO Yong-qiang LI Shun-da CHEN Shu-yu YANG Xue-ke YUAN Yun . Effect of gastrodin on M2 type polarization in activated microglia via p38 MAPK signaling[J]. Acta Anatomica Sinica, 2024, 55(6): 657-666.

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天麻素经p38 MAPK通路对M2型小胶质细胞极化的影响

Effect of gastrodin on M2 type polarization in activated microglia via p38 MAPK signaling

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