白三烯B4/白三烯B4受体通路在脑缺血损伤发生机制中的研究进展
李慧敏 向净匀 吴杰 王琰 周爽 史永恒 王川 王斌
陕西中医药大学药学院中药药理教研室,陕西咸阳 712046
Research progress of leukotriene B4/leukotriene B4 receptor pathway in the mechanism of cerebral ischemic injury
LI Huimin XIANG Jingyun WU Jie WANG Yan ZHOU Shuang SHI Yongheng WANG Chuan WANG Bin
Department of Chinese Medicine Pharmacology, College of Pharmacy, Shaanxi University of Chinese Medicine, Shaanxi Province, Xianyang 712046, China
摘要 白三烯B4(LTB4)是5-脂氧合酶代谢花生四烯酸的下游产物之一,是一种强效的促炎症脂质介质。通过对已有文献的整理,发现在脑缺血损伤后神经元、小胶质细胞及星形胶质细胞释放LTB4促进中性粒细胞浸润释放炎症因子,导致脑缺血继发性脑损伤。深入研究靶向LTB4-BLTR轴在脑缺血损伤后炎症反应中的作用及机制,可寻找新的有效治疗脑缺血损伤的治疗药物。
关键词 :
脑缺血 ,
白三烯B4 ,
白三烯B4受体 ,
中性粒细胞
Abstract :Leukotriene B4 (LTB4) is one of the downstream products of arachidonic acid metabolized by 5-lipoxygenase, and it is a potent pro-inflammatory lipid mediator. By sorting out the existing literature, it is found that after cerebral ischemia, neurons, microglia and astrocytes release LTB4, which promotes neutrophil infiltration and release inflammatory factors, leading to secondary brain injury after cerebral ischemia. Further study on the role and mechanism of targeting LTB4-BLTR axis in inflammatory response after cerebral ischemia injury can find new effective therapeutic drugs for cerebral ischemia injury.
Key words :
Cerebral ischemia
Leukotriene B4
Leukotriene B4 receptors
Neutrophil
基金资助: 国家自然科学基金资助项目(81473385);
陕西省自然科学基础研究计划项目(2018JM7111);
陕西中医药大学学科创新团队项目(2019-YL13)。
通讯作者:
王斌(1978-),男,博士,教授,硕士生导师;研究方向:心脑血管疾病药理学。
作者简介 : 李慧敏(1996-),女,陕西中医药大学药学院2018级中药药理学专业在读硕士研究生;研究方向:心脑血管疾病药理学。
引用本文:
李慧敏 向净匀 吴杰 王琰 周爽 史永恒 王川 王斌. 白三烯B4/白三烯B4受体通路在脑缺血损伤发生机制中的研究进展[J]. 中国医药导报, 2020, 17(31): 50-53.
LI Huimin XIANG Jingyun WU Jie WANG Yan ZHOU Shuang SHI Yongheng WANG Chuan WANG Bin. Research progress of leukotriene B4/leukotriene B4 receptor pathway in the mechanism of cerebral ischemic injury. 中国医药导报, 2020, 17(31): 50-53.
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[1] Ding Y,Clark JC. Cerebrovascular injury in stroke [J]. Neurol Res,2006,28(1):3-10. doi:10.1179/016164106X91799.
[2] Frangogiannis NG. Chemokines in ischemia and reperfusion [J]. Thromb Haemost,2007,97(5):738-747.
[3] Owens T,Babcock AA,Millward JM,et al. Cytokine and chemokine inter-regulation in the inflamed or injured CNS [J]. Brain Res Brain Res Re,2005,48(2):178-184. doi:10.1016/j.brainresrev.2004.12.007.
[4] Danton GH,Dietrich WD. Inflammatory mechanisms after ischemia and stroke [J]. J Neuropathol Exp Neurol,2003, 62(2):127-136. doi:10.1093/jnen/62.2.127.
[5] 宋亚刚,叶林峰,吃安坤,等.5-脂氧酶在脑缺血再灌注损伤中的机制探讨[J].中南药学,2016,14(4):407-410.
[6] 刘寒,张欢欢,康亚国,等.黄芩苷与栀子苷组合物对脑缺血损伤大鼠5-LOX/CysLTs/CysLT通路的影响[J].中成药,2018,40(5):1020-1025.
[7] 李敏,武璞,吕腾,等.醒脑静提取物对脑缺血再灌注炎性损伤5-LOX-CysLTs-CysLT通路的影响[J].中药药理与临床,2015,31(6):131-134.
[8] 何林,刘寒,高原雪,等.5-LOX-CysLTs-CysLTsR表达规律及黄芩苷-栀子苷配伍对大鼠脑缺血抗炎作用机制研究[J].陕西中医药大学学报,2019,42(3):57-63.
[9] Samuelsson B,Dahlen SE,Lindgren JA,et al. Leukotrienes and lipoxins:structures,biosynthesis,and biological effects [J]. Science,1987,237(4819):1171-1176. doi:10.1126/science.2820055.
[10] Kihara Y,Yokomizo T,Kunita A,et al. The leukotriene B4 receptor,BLT1,is required for the induction of experimental autoimmune encephalomyelitis [J]. Biochem Biophys Res Commun,2010,394(3):673-678. doi:10.1016/j.bbrc.2010.03.049.
[11] Saiwai H,Ohkawa Y,Yamada H,et al. The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury [J]. Am J Pathol,2010,176(5):2352-2366. doi:10.2353/ajpath.2010.090839.
[12] Asahara M,Ito N,Yokomizo T,et al. The absence of the leukotriene B4 receptor BLT1 attenuates peripheral inflammation and spinal nociceptive processing following intraplantar formalin injury [J]. Mol Pain,2015,11:11. doi:10.1186/s12990-015-0010-9.
[13] Shimizu T,Wolfe LS. Arachidonic acid cascade and signal transduction [J]. J Neurochem,1990,55(1):1-15. doi:10.1111/j.1471-4159.1990.tb08813.x.
[14] Salemi G,Gueli MC,D′Amelio M,et al. Blood levels of homocysteine,cysteine,glutathione,folic acid,and vitamin B12 in the acute phase of atherothrombotic stroke [J]. Neurol Sci,2009,30(4):361-364. doi:10.1007/s10072-009-0090-2.
[15] Rosenblum WI. Constricting effect of leukotrienes on cerebral arterioles of mice [J]. Stroke,1985,16(2):262-263. doi:10.1161/01.str.16.2.262.
[16] Woodward DF,Weichman BM,Gill CA,et al. The effect of synthetic leukotrienes on tracheal microvascular permeability [J]. Prostaglandins,1983,25(1):131-142. doi:10.1016/0090-6980(83)90142-9.
[17] Lin AH,Ruppel PL,Gorman RR. Leukotriene B4 binding to human neutrophils [J]. Prostaglandins,1984,28(6):837-849. doi:10.1016/0090-6980(84)90038-8.
[18] Cho KJ,Seo JM,Shin Y,et al. Blockade of airway inflammation and hyperresponsiveness by inhibition of BLT2,a low-affinity leukotriene B4 receptor [J]. Am J Respir Cell Mol Biol,2010,42(3):294-303. doi:10.1165/rcmb.2008-0445OC.
[19] Matsunaga Y,Fukuyama S,Okuno T,et al. Leukotriene B4 receptor BLT2 negatively regulates allergic airway eosinophilia [J]. FASEB J,2013,27(8):3306-3314. doi:10.1096/fj.12-217000.
[20] 马红岗,潘琴妹,朱斐斐,等.白三烯B4、颈动脉斑块性质与进展性缺血性脑卒中相关性[J].中国临床药理学与治疗学,2017,22(6):689-693.
[21] 马红岗,朱斐斐,王亚仙.急性脑梗死患者颈动脉硬化与血清LTB4、MMP-9表达水平的相关性研究[J].中国医药导报,2017,14(23):52-55.
[22] 马红岗,潘琴妹,朱斐斐,等.白三烯B4与脑动脉硬化所致进展性缺血性脑卒中的相关性分析[J].全科医学临床与教育,2017,15(2):153-155.
[23] Chan SJ,Ng MPE,Zhao H,et al. Early and sustained increases in leukotriene B4 levels are associated with poor clinical outcome in ischemic stroke patients [J]. Neurotherapeutics,2020,17(1):282-293. doi:10.1007/s13311-019-00787-4.
[24] 方美凤,谭峰,王学文.细胞因子信号转导抑制因子3和白三烯B4及白细胞介素6与脑梗死体积的相关性[J].中华老年心脑血管病杂志,2018,20(10):1095-1096.
[25] Bednar MM,Raymond S,McAuliffe T,et al. The role of neutrophils and platelets in a rabbit model of thromboembolic stroke [J]. Stroke,1991,22(1):44-50. doi:10.1161/01.str.22.1.44.
[26] Dutka AJ,Kochanek PM,Hallenbeck JM. Influence of granulocytopenia on canine cerebral ischemia induced by air embolism [J]. Stroke,1989,20(3):390-395. doi:10. 1161/01.str.20.3.390.
[27] Barone FC,Schmidt DB,Hillegass LM,et al. Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia [J]. Stroke,1992,23(9):1337-1347. doi:10.1161/01.str.23.9.1337.
[28] Yagami T,Yamamoto Y,Kohma H. Leukotriene receptor antagonists,LY293111 and ONO-1078,protect neurons from the sPLA2-IB-induced neuronal cell death independently of blocking their receptors [J]. Neurochem Int,2013,63(3):163-171. doi:10.1016/j.neuint.2013.06. 009.
[29] Wang G,Zhang J,Sun H,et al. Genetic variation in members of the leukotrienes biosynthesis pathway confers risk of ischemic stroke in Eastern Han Chinese [J]. Prostaglandins Leukot Essent Fatty Acids,2012,87(6):169-175. doi:10.1016/j.plefa.2012.09.005.
[30] 侯树刚,孙瑛,刘丽君,等.白三烯A4水解酶基因多态性与缺血性脑卒中相关性[J].齐鲁医学杂志,2013,28(4):325-327.
[31] 袁荣荣.LTA4H基因多态性对动脉粥样硬化型脑梗死的影响[D].青岛:青岛大学,2014.
[32] Zhou Y,Wei EQ,Fang SH,et al. Spatio-temporal properties of 5-lipoxygenase expression and activation in the brain after focal cerebral ischemia in rats [J]. Life Sci,2006,79(17):1645-1656. doi:10.1016/j.lfs.2006.05.022.
[33] Park JH,Cho JH,Ahn JH,et al. Neuronal loss and gliosis in the rat striatum subjected to 15 and 30 minutes of middle cerebral artery occlusion [J]. Metab Brain Dis,2018,33(3):775-784. doi:10.1007/s11011-018-0192-8.
[34] Moreland DB,Soloniuk DS,Feldman MJ. Leukotrienes in experimental spinal cord injury [J]. Surg Neurol,1989,31(4):277-280. doi:10.1016/0090-3019(89)90052-9.
[35] Hartung HP,Heininger K,Toyka KV. Primary rat astroglial cultures can generate leukotriene B4 [J]. J Neuroimmunol,1988,19(3):237-243. doi:10.1016/0165-5728(88)90005-7.
[36] Tu XK,Yang WZ,Wang CH,et al. Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats [J]. Inflammation,2010,33(5):344-352. doi:10.1007/s10753-010-9191-6.
[37] 叶振南.蛛网膜下腔出血后LTB4-BLT1轴介导中性粒细胞浸润的临床与基础研究[D].广州:南方医科大学,2017.
[38] Hijioka M,Anan J,Ishibashi H,et al. Inhibition of leukotriene B4 action mitigates intracerebral hemorrhage-associated pathological events in mice [J]. J Pharmacol Exp Ther,2017,360(3):399-408. doi:10.1124/jpet.116.238824.
[39] Arita M,Ohira T,Sun YP,et al. Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation [J]. J Immunol,2007,178(6):3912-3917. doi:10.4049/jimmunol.178.6.3912.
[40] Papayianni A,Serhan CN,Brady HR. Lipoxin A4 and B4 inhibit leukotriene-stimulated interactions of human neutrophils and endothelial cells [J]. J Immunol,1996, 156(6):2264-2272.
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