调控缺血性脑卒中小胶质细胞极化的药物研究进展

doi:10.3969/j.issn.1006-9771.2020.05.013

《中国康复理论与实践》 ›› 2020, Vol. 26 ›› Issue (5): 559-562.doi: 10.3969/j.issn.1006-9771.2020.05.013

调控缺血性脑卒中小胶质细胞极化的药物研究进展

邓杜萍¹,范金¹,谢晓龙¹,李凌鑫²()

1.成都中医药大学养生康复学院,四川成都市 610075
2.四川大学华西医院康复科,四川成都市 610041

收稿日期:2019-08-13 修回日期:2019-10-14 出版日期:2020-05-25 发布日期:2020-05-29
通讯作者: 李凌鑫 E-mail:lilingxin111@163.com
作者简介:邓杜萍(1991-),女,汉族,四川眉山市人,硕士研究生,主要研究方向：缺血性脑卒中康复治疗。
基金资助:
1.四川省科技厅支撑计划项目(2016SZ0039);2.四川省科技厅重点研发项目(18ZDYF2033)

Advances in Drugs for Microglia Polarization after Ischemic Stroke (review)

DENG Du-ping¹,FAN Jin¹,XIE Xiao-long¹,LI Ling-xin²()

1. College of Health Care and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China
2. Department of Rehabilitation, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China

Received:2019-08-13 Revised:2019-10-14 Published:2020-05-25 Online:2020-05-29
Contact: LI Ling-xin E-mail:lilingxin111@163.com
Supported by:
Sichuan Science and Technology Department Support Plan(2016SZ0039);Sichuan Science and Technology Department Research and Development Key Project(18ZDYF2033)

摘要/Abstract

摘要：

缺血性脑卒中后,小胶质细胞被激活,表现为M1和M2两种极化表型,许多药物可以促进缺血性脑卒中后小胶质细胞由M1型向M2型转化,如芬戈莫德、3-正丁基苯酞及其衍生物、姜黄素、西地那非、Exendin-4、雷公藤红素、Omega-3多元不饱和脂肪酸、Malibatol A、红景天苷等。

关键词: 缺血性脑卒中, 小胶质细胞, 表型, 药物, 综述

Abstract:

Microglia cells are activated after ischemic stroke, and polarized phenotypes of M1 and M2. Some drugs, such as fingolimod, 3-N-butylphthalide, curcumin, sildenafil, exendin-4, celastrol, omega-3 fatty acids, malibatol A, salidroside, etc., can transfer the polarization from M1 to M2, and may benefit the outcome of ischemic stroke.

Key words: ischemic stroke, microglia, phenotype, drugs, review

中图分类号:

R743.32

邓杜萍,范金,谢晓龙,李凌鑫. 调控缺血性脑卒中小胶质细胞极化的药物研究进展[J]. 《中国康复理论与实践》, 2020, 26(5): 559-562.

DENG Du-ping,FAN Jin,XIE Xiao-long,LI Ling-xin. Advances in Drugs for Microglia Polarization after Ischemic Stroke (review)[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(5): 559-562.

参考文献 54

[1]	Simone V, Arturo C, Marco A, et al. Postischemic inflammation in acute stroke[J]. J Clin Neurol, 2017, 13(1):1-9. doi: 10.3988/jcn.2017.13.1.1 pmid: 28079313
[2]	Umekawa T, Osman A M, Han W, et al. Resident microglia, rather than blood-derived macrophages, contribute to the earlier and more pronounced inflammatory reaction in the immature compared with the adult hippocampus after hypoxia-ischemia[J]. Glia, 2015, 63(12):2220-2230. doi: 10.1002/glia.v63.12
[3]	Kierdorf K, Erny D, Goldmann T, et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways[J]. Nat Neurosci, 2013, 16(3):273-280. doi: 10.1038/nn.3318 pmid: 23334579
[4]	Hu X, Leak R K, Shi Y, et al. Microglial and macrophage polarization—new prospects for brain repair[J]. Nat Rev Neurol, 2014, 11(1):56-64. doi: 10.1038/nrneurol.2014.207
[5]	Hu X, Li P, Guo Y, et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia[J]. Stroke, 2012, 43(11):3063-3070. doi: 10.1161/STROKEAHA.112.659656
[6]	Xiong X Y, Liu L, Yang Q W. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis during stroke[J]. Prog Neurobiol, 2016, 142:23-44. doi: 10.1016/j.pneurobio.2016.05.001
[7]	Benakis C, Garcia-Bonilla L, Iadecola C, et al. The role of microglia and myeloid immune cells in acute cerebral ischemia[J]. Front Cell Neurosci, 2015, 8:461.
[8]	Chu H X, Broughton B R S, Ah Kim H, et al. Evidence that CLy6C(hi) monocytes are protective in acute ischemic stroke by promoting M2 macrophage polarization[J]. Stroke, 2015, 46(7):1929-1937. doi: 10.1161/STROKEAHA.115.009426
[9]	Kanazawa M, Miura M, Toriyabe M, et al. Microglia preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic rats[J]. Sci Rep, 2017, 7:42582. doi: 10.1038/srep42582 pmid: 28195185
[10]	Cohen J A, Chun J. Mechanisms of fingolimod’s efficacy and adverse effects in multiple sclerosis[J]. Ann Neurol, 2011, 69(5):759-777. doi: 10.1002/ana.v69.5
[11]	Gaire B P, Song M R, Choi J W. Sphingosine 1-phosphate receptor subtype 3 (S1P3) contributes to brain injury after transient focal cerebral ischemia via modulating microglial activation and their M1 polarization[J]. J Neuroinflammation, 2018, 15(1):284. doi: 10.1186/s12974-018-1323-1
[12]	Li X, Wang M H, Qin C, et al. Fingolimod suppresses neuronal autophagy through the mTOR/p70S6K pathway and alleviates ischemic brain damage in mice[J]. PLoS One, 2017, 12(11):e0188748. doi: 10.1371/journal.pone.0188748
[13]	Kraft P, Gob E, Gobel K, et al. FTY720 ameliorates acute ischemic stroke in mice by reducing thrombo-inflammation but not by direct neuroprotection[J]. Stroke, 2013, 44(11):3202-3210. doi: 10.1161/STROKEAHA.113.002880
[14]	Campos F, Qin T, Castillo J, et al. Fingolimod reduces hemorrhagic transformation associated with delayed tissue plasminogen activator treatment in a mouse thromboembolic model[J]. Stroke, 2013, 44(2):505-511. doi: 10.1161/STROKEAHA.112.679043
[15]	Qin C, Fan W H, Liu Q, et al. Fingolimod protects against ischemic white matter damage by modulating microglia toward M2 polarization via STAT3 pathway[J]. Stroke, 2017, 48(12):3336-3346. doi: 10.1161/STROKEAHA.117.018505
[16]	Ali A I, Jing G Y. A review of recent advances in neuroprotective potential of 3-N-butylphthalide and its derivatives[J]. Biomed Res Int, 2016, 2016:1-9.
[17]	Zhao H, Yun W, Zhang Q, et al. Mobilization of circulating endothelial progenitor cells by DL-3-N-butylphthalide in acute ischemic stroke patients[J]. J Stroke Cerebrovasc Dis, 2016, 25(4):752-760. doi: 10.1016/j.jstrokecerebrovasdis.2015.11.018
[18]	Hu J, Wen Q, Wu Y, et al. The effect of butylphthalide on the brain edema, blood-brain barrier of rats after focal cerebral infarction and the expression of Rho A[J]. Cell Biochem Biophys, 2014, 69(2):363-368. doi: 10.1007/s12013-013-9808-0
[19]	Li F, Ma Q, Zhao Q, et al. L-3-N-butylphthalide reduces ischemic stroke injury and increases M2 microglial polarization[J]. Metab Brain Dis, 2018, 33(6):1995-2003. doi: 10.1007/s11011-018-0307-2
[20]	Xie C J, Gu A P, Cai J, et al. Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke[J]. Brain Behav, 2018, 8(2):e00921. doi: 10.1002/brb3.2018.8.issue-2
[21]	Miao Y, Zhao S, Gao Y, et al. Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: the possible role of Sirt1 signaling[J]. Brain Res Bull, 2016, 121:9-15. doi: 10.1016/j.brainresbull.2015.11.019
[22]	Wu J, Li Q, Wang X, et al. Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway[J]. PLoS One, 2013, 8(3):e59843. doi: 10.1371/journal.pone.0059843
[23]	Liu Z, Ran Y, Huang S, et al. Curcumin protects against ischemic stroke by titrating microglia/macrophage polarization[J]. Front Aging Neurosci, 2017, 9:233. doi: 10.3389/fnagi.2017.00233
[24]	Zhang R, Wang Y, Zhang L, et al. Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats[J]. Stroke, 2002, 33(11):2675-2680. doi: 10.1161/01.STR.0000034399.95249.59
[25]	Ding G, Jiang Q, Li L, et al. Magnetic resonance imaging investigation of axonal remodeling and angiogenesis after embolic stroke in sildenafil-treated rats[J]. J Cereb Blood Flow Metab, 2008, 28(8):1440-1448. doi: 10.1038/jcbfm.2008.33
[26]	Barros-Minones L, Orejana L, Goni-Allo B, et al. Modulation of the ASK1-MKK3/6-p38/MAPK signalling pathway mediates sildenafil protection against chemical hypoxia caused by malonate[J]. Br J Pharmacol, 2013, 168(8):1820-1834. doi: 10.1111/bph.12071
[27]	Barros-Miñones L, Martín-de-Saavedra D, Perez-Alvarez S, et al. Inhibition of calpain-regulated p35/cdk5 plays a central role in sildenafil-induced protection against chemical hypoxia produced by malonate[J]. Biochim Biophys Acta, 2013, 1832(6):705-717. doi: 10.1016/j.bbadis.2013.02.002 pmid: 23415811
[28]	Moretti R, Leger P L, Besson Valérie C, et al. Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain[J]. J Neuroinflammation, 2016, 13(1):95. doi: 10.1186/s12974-016-0560-4
[29]	Darsalia V, Mansouri S, Ortsäter H, et al. Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in type 2 diabetic rats[J]. Clin Sci (Lond), 2011, 122(10):473-483. doi: 10.1042/CS20110374
[30]	Darsalia V, Hua S, Larsson M, et al. Exendin-4 reduces ischemic brain injury in normal and aged type 2 diabetic mice and promotes microglial M2 polarization[J]. PLoS One, 2014, 9(8):e103114. doi: 10.1371/journal.pone.0103114
[31]	Kim S, Jeong J, Jung H S, et al. Anti-inflammatory effect of glucagon like peptide-1 receptor agonist, exendin-4, through modulation of IB1/JIP1 expression and JNK signaling in stroke[J]. Exp Neurobiol, 2017, 26(4):227-239. doi: 10.5607/en.2017.26.4.227
[32]	Teramoto S, Miyamoto N, Yatomi K, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia[J]. J Cereb Blood Flow Metab, 2011, 31(8):1696-1705. doi: 10.1038/jcbfm.2011.51
[33]	Chen F, Wang W, Ding H, et al. The glucagon-like peptide-1 receptor agonist exendin-4 ameliorates warfarin-associated hemorrhagic transformation after cerebral ischemia[J]. J Neuroinflammation, 2016, 13(1):204. doi: 10.1186/s12974-016-0661-0
[34]	Lee C H, Yan B C, Choi J H, et al. Ischemia-induced changes in glucagon-like peptide-1 receptor and neuroprotective effect of its agonist, exendin-4, in experimental transient cerebral ischemia[J]. J Neurosci Res, 2011, 89(7):1103-1113. doi: 10.1002/jnr.22596
[35]	Barker E C, Kim B G, Yoon J H, et al. Potent suppression of both spontaneous and carcinogen-induced colitis-associated colorectal cancer in mice by dietary celastrol supplementation[J]. Carcinogenesis, 2018, 39(1):36-46. doi: 10.1093/carcin/bgx115 pmid: 29069290
[36]	Ren B, Liu H, Gao H, et al. Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR[J]. Oncotarget, 2017, 8(54):93039-93050. doi: 10.18632/oncotarget.21750 pmid: 29190976
[37]	Astry B, Venkatesha S H, Laurence A, et al. Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ[J]. Clin Immunol, 2015, 157(2):228-238. doi: 10.1016/j.clim.2015.01.011
[38]	Luo D, Guo Y, Cheng Y, et al. Natural product celastrol suppressed macrophage M1 polarization against inflammation in diet-induced obese mice via regulating Nrf2/HO-1, MAP kinase and NF-κB pathways[J]. Aging, 2017, 9(10):2069-2082. doi: 10.18632/aging.v9i10
[39]	Bai S, Hu Z, Yang Y, et al. Anti‐inflammatory and neuroprotective effects of Triptolide via the NF‐κB signaling pathway in a rat MCAO model[J]. Anat Rec, 2016, 299(2):256-266. doi: 10.1002/ar.23293
[40]	Jiang M, Liu X, Zhang D, et al. Celastrol treatment protects against acute ischemic stroke-induced brain injury by promoting an IL-33/ST2 axis-mediated microglia/macrophage M2 polarization[J]. J Neuroinflammation, 2018, 15(1):78. doi: 10.1186/s12974-018-1124-6
[41]	Zhang M, Wang S, Mao L, et al. Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1[J]. J Neurosci, 2014, 34(5):1903-1915. doi: 10.1523/JNEUROSCI.4043-13.2014
[42]	Yang B, Ren X L, Huang H, et al. Circulating long-chain n-3 polyunsaturated fatty acid and incidence of stroke: a meta-analysis of prospective cohort studies[J]. Oncotarget, 2017, 8(48):83781-83791. doi: 10.18632/oncotarget.19530 pmid: 29137382
[43]	Mengfei C, Wenting Z, Zhongfang W, et al. Promoting neurovascular recovery in aged mice after ischemic stroke - prophylactic effect of omega: 3 polyunsaturated fatty acids[J]. Aging Dis, 2017, 8(5):531-545. doi: 10.14336/AD.2017.0520 pmid: 28966799
[44]	Dirk B, Konrad K, Nicole F, et al. Intravenous treatment with a long-chain omega-3 lipid emulsion provides neuroprotection in a murine model of ischemic stroke: a pilot study[J]. PLoS One, 2016, 11(11):e0167329. doi: 10.1371/journal.pone.0167329
[45]	Jiang X, Pu H, Hu X, et al. A post-stroke therapeutic regimen with omega-3 polyunsaturated fatty acids that promotes white matter integrity and beneficial microglial responses after cerebral ischemia[J]. Transl Stroke Res, 2016, 7(6):548-561. doi: 10.1007/s12975-016-0502-6
[46]	Yang W, Chen X, Pan J, et al. Malibatol A protects against brain injury through reversing mitochondrial dysfunction in experimental stroke[J]. Neurochem Int, 2015, 80:33-40. doi: 10.1016/j.neuint.2014.11.003
[47]	Pan J, Jin J L, Ge H M, et al. Malibatol A regulates microglia M1/M2 polarization in experimental stroke in a PPARγ-dependent manner[J]. J Neuroinflammation, 2015, 12(1):51. doi: 10.1186/s12974-015-0270-3
[48]	Weng L, Wu Z, Zheng W, et al. Malibatol A enhances alternative activation of microglia by inhibiting phosphorylation of mammalian Ste20-like kinase 1 in OGD-BV-2 cells[J]. Neurol Res, 2016, 38:342-348. doi: 10.1080/01616412.2016.1174423
[49]	Han J, Xiao Q, Lin Y H, et al. Neuroprotective effects of salidroside on focal cerebral ischemia/reperfusion injury involve the nuclear erythroid 2-related factor 2 pathway[J]. Neural Regen Res, 2015, 10(12):1989-1996. doi: 10.4103/1673-5374.172317
[50]	Liu X, Wen S, Yan F, et al. Salidroside provides neuroprotection by modulating microglial polarization after cerebral ischemia[J]. J Neuroinflammation, 2018, 15(1):39. doi: 10.1186/s12974-018-1081-0
[51]	Wei H, Sun T, Tian Y, et al. Ginkgolide B modulates BDNF expression in acute ischemic stroke[J]. J Korean Neurosurg Soc, 2017, 60(4):391-396. doi: 10.3340/jkns.2016.1010.018
[52]	He Y, Ma X, Li D, et al. Thiamet G mediates neuroprotection in experimental stroke by modulating microglia/macrophage polarization and inhibiting NF-κB p65 signaling[J]. J Cereb Blood Flow Metab, 2017, 37(8):2938-2951. doi: 10.1177/0271678X16679671
[53]	Potey C, Ouk T, Petrault O, et al. Early treatment with atorvastatin exerts parenchymal and vascular protective effects in experimental cerebral ischaemia[J]. Br J Pharmacol, 2015, 172(21):5188-5198. doi: 10.1111/bph.2015.172.issue-21
[54]	Yew W P, Djukic N D, Jayaseelan J S P, et al. Early treatment with minocycline following stroke in rats improves functional recovery and differentially modifies responses of peri-infarct microglia and astrocytes[J]. J Neuroinflammation, 2019, 16(1):6. doi: 10.1186/s12974-018-1379-y

调控缺血性脑卒中小胶质细胞极化的药物研究进展

Advances in Drugs for Microglia Polarization after Ischemic Stroke (review)

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 54

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	邵伟婷, 雷江华. 反应中断再定向干预孤独症谱系障碍儿童刻板语言的效果：Scoping综述[J]. 《中国康复理论与实践》, 2024, 30(1): 10-20.
[2]	王航宇, 葛可可, 范永红, 都丽露, 邹敏, 封磊. 基于ICD-11和ICF主动式音乐疗法改善认知障碍老年人认知功能的系统综述[J]. 《中国康复理论与实践》, 2024, 30(1): 36-43.
[3]	闻嘉宁, 金秋艳, 张琦, 李杰, 司琦. 认知参与型身体活动对发展儿童青少年执行功能的效果：基于ICF的系统综述[J]. 《中国康复理论与实践》, 2024, 30(1): 44-53.
[4]	葛可可, 范永红, 王航宇, 都丽露, 李长江, 邹敏. 失眠老年人正念干预健康效益的系统综述[J]. 《中国康复理论与实践》, 2024, 30(1): 54-60.
[5]	张婧雅, 邹敏, 孙宏伟, 孙昌隆, 朱峻同. 听障儿童青少年焦虑或抑郁情绪心理干预效果的系统综述[J]. 《中国康复理论与实践》, 2023, 29(9): 1004-1011.
[6]	王俊宇, 杨永, 袁逊, 谢婷, 庄洁. 高强度间歇训练对健康儿童青少年执行功能效果的系统综述[J]. 《中国康复理论与实践》, 2023, 29(9): 1012-1020.
[7]	魏晓微, 杨剑, 魏春艳. 特殊教育学校孤独症谱系障碍儿童参与适应性瑜伽活动的心理与行为效益的系统综述[J]. 《中国康复理论与实践》, 2023, 29(9): 1021-1028.
[8]	杨亚茹, 杨剑. 基于WHO-HPS架构学校身体活动相关健康服务及其健康效益：系统综述的系统综述[J]. 《中国康复理论与实践》, 2023, 29(9): 1040-1047.
[9]	史佳伟, 李凌宇, 杨浩杰, 王琴潞, 邹海欧. 预康复对全膝关节置换术后患者的有效性：系统综述的系统综述[J]. 《中国康复理论与实践》, 2023, 29(9): 1057-1064.
[10]	蒋长好, 黄辰, 高晓妍, 戴元富, 赵国明. 神经反馈训练对老年人认知功能效果的系统综述[J]. 《中国康复理论与实践》, 2023, 29(8): 903-909.
[11]	魏晓微, 杨剑, 魏春艳, 贺启令. 学校环境下适应性体育课程促进智力与发展性残疾儿童心理运动发展的系统综述[J]. 《中国康复理论与实践》, 2023, 29(8): 910-918.
[12]	张园, 杨剑. 基于世界卫生组织健康促进学校架构的学校健康服务及效果：Scoping综述[J]. 《中国康复理论与实践》, 2023, 29(7): 791-799.
[13]	王少璞, 陈钢. 基于世界卫生组织健康促进学校架构的心理行为健康服务及其健康效益：系统综述的系统综述[J]. 《中国康复理论与实践》, 2023, 29(7): 800-807.
[14]	蒋长好, 高晓妍. 短时身体活动对儿童认知功能影响的系统综述[J]. 《中国康复理论与实践》, 2023, 29(6): 667-672.
[15]	邓婷, 陈敬绵, 刘小蒙, 姚晓华, 刘芦姗, 何威, 张通, 芦海涛. 轻中度急性缺血性脑卒中并发卒中相关性肺炎的危险因素分析[J]. 《中国康复理论与实践》, 2023, 29(6): 708-713.