大鼠脑缺血再灌注后环氧合酶-2促进E-选择素表达增多及灯盏花素的脑保护作用

doi:10.16098/j.issn.0529-1356.2018.06.001

摘要/Abstract

摘要：

目的观察大鼠脑缺血再灌后环氧合酶-2（COX-2）对E-选择素（E-selectin）表达的影响及灯盏花素对COX-2及E-selectin的影响，探讨脑缺血再灌注损伤后， COX-2加重脑损伤的机制及灯盏花素的脑保护作用。方法 48只清洁级SD大鼠随机分为假手术组、生理盐水组、SC-58125组、灯盏花素治疗组，在缺血2 h再灌注24 h时，神经功能学评分观察大鼠神经行为的变化，2,3,5-氯化三苯四氮唑（TTC）染色观察大鼠脑梗死灶体积的变化；免疫印迹法和酶联免疫吸附测定检测COX-2及E-selectin表达的变化。结果 SC-58125组和灯盏花素治疗组神经行为学评分明显降低，脑组织梗死体积显著减小，COX-2和E-selectin的表达明显下降。结论脑缺血再灌注后，COX-2可能通过促进E-selectin的表达加重缺血区的炎症反应；灯盏花素可能通过抑制COX-2及E-selectin的表达而发挥脑保护作用。

关键词: 大脑, 缺血再灌注损伤, 环氧合酶-2, E-选择素, 灯盏花素, 免疫印迹法, 大鼠

Abstract:

Objective To investigate the mechanisms of cyclooxygenase-2 (COX-2) aggravating cerebral injury and the protective effects of breviscapine after cerebral ischemic-reperfusion injury, by observing the effect of COX-2 on the expression of E-selectin and the effect of breviscapine on the expression of COX-2 and E-selectin. Methods Forty-eight SD rats were randomly divided into sham group, saline group, SC-58125 group and breviscapine treatment group, at ischemia hour 2/reperfusion hour 24. Nerve function scores were used to observe the neurobehavioral changes of rats, 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to assess the changes of cerebral infarction volume. Western blotting and enzyme-linked immunosorbent assay were used to detect the expression of COX-2 and E-selectin. Results In SC-58125 group and breviscapine treatment group, nerve function scores, cerebral infarction volume and COX-2 and E-selectinwere significantly decreased. Conclusion COX-2 aggravates inflammatory response of ischemia area by promoting the expression of E-selectin; breviscapine may play a protective role by inhibiting the expression of COX-2 and E-selectin.

Key words: Brain, Ischemia-reperfusion injury, Cyclooxygenase-2, E-selectin, Breviscapine, Western blotting, Rat

杨迎春任占川陈新骥 . 大鼠脑缺血再灌注后环氧合酶-2促进E-选择素表达增多及灯盏花素的脑保护作用[J]. 解剖学报, 2018, 49(6): 703-707.

YANG Ying-chun REN Zhan-chuan CHEN Xin-ji . Cyclooxygenase-2 promoting the expression of E-selectin and the cerebral protective effects of breviscapine after cerebral ischemic-reperfusion injury in rats[J]. Acta Anatomica Sinica, 2018, 49(6): 703-707.

参考文献

［1］ Shi L, Cao HM, Li Y, et al. Electroacupuncture improves neurovascular unit reconstruction by promoting collateral circulation and angiogenesis［J］. Neural Regen Res, 2017,12(12):2000-2006.

［2］ Yang YCh, Ren ZhCh, Liang YG. Study of the expression of cyclooxygenase-2, malonic dialdehyde and the protective effect of Tetramethylpyrazine after cerebral ischemic-reperfusion in rat［J］. Acth Anatomica Sinica, 2009, 40(6):886-890.(in Chinese)

杨迎春, 任占川, 梁勇刚. 大鼠脑缺血再灌注后诱导型环氧合酶和丙二醛的表达及川芎嗪的干预作用［J］. 解剖学报, 2009, 40(6):886-890.

［3］ Zager RA, Johnson AC, Frostad KB. Acute hepatic ischemic-reperfusion injury induces a renal cortical “stress response,” renal “cytoresistance,” and an endotoxin hyperresponsive state［J］. Am J Physiol Renal Physiol, 2014,307(7): F859-F862.

［4］ Tu QY, Cao H, Zhong W, et al. Atorvastatin protects against cerebral ischemia/reperfusion injury through anti-inflammatory and antioxidant effects［J］. Neural Regen Res, 2014, 9(3): 268-275.

［5］ Gao HJ, Liu PF, Li PW, et al. Ligustrazine monomer against cerebral ischemia/reperfusion injury［J］. Neural Regen Res, 2015,10(5): 835-840.

［6］ Rodrigo R, Fernández-Gajardo R, Gutiérrez R, et al. Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities［J］. CNS Neurol Disord Drug Targets, 2013, 12(5):698-714.

［7］ Liu YH, Lin B, Fu XH, et al. Clinical study on the treatment of ischemic cerebral apoplexy with breviscapine injection ［J］. Modern Diagnosis and Treatment, 2013,24(3):554-555. (in Chinese)

刘毅华，林斌，付秀华，等.注射用灯盏花素治疗缺血性脑卒中的临床研究［J］.现代诊断与治疗,2013,24（3）:554-555.

［8］ Zea Longa EL, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without caraniectomy in rats［J］. Stroke, 1989, 20(1): 87-91.

［9］ Ye Z, Wang N, Xia P, et al. Delayed administration of parecoxib,a specific COX-2 inhibitor, attenuated postischemic neuronal apoptosis by phosphorylation Akt and GSK-3β［J］. Neurochem Res, 2012,37(2):321-329.

［10］Vaibhav K, Shrivastava P, Javed H, et al. Piperine suppresses cerebral ischemia-reperfusion-induced inflammation through the repression of COX-2,NOS-2,and NF-κB in middle cerebral artery occlusion rat model［J］.Mol CellBiochem,2012,367(1-2):73-84.

［11］Shang AJ, Ying Y, Wang HY, et al. Upregulation of neuroglobin expression and changes in serum redox indices in a rat model of middle cerebral artery occlusion［J］. Mol Med Rep, 2015,12(2): 1695-1698.

［12］Lu H, Wang B, Cui N, et al. Artesunate supresses oxidative and inflammatory processes by activating Nrf 2 and RO-|dependent p38MAPK and protects against cerebral ischemia-reperfusion injury［J］. Mol Med Rep, 2018, 17(5):6639-6646.

［13］Liu TJ, Zhang JC, Gao XZ, et al. Effect of sevoflurane on the ATPase activity of hippocampal neurons in a rat model of cerebral isechmia-reperfusion injury via the Camp-PKA signaling pathway［J］. Kaohsiung J Med Sci, 2018,34(1):22-33.

［14］Kim JH, Kim JY, Jung JY, et al. Endogenous agmatine induced by ischemic preconditioning regulates ischemic tolerance following cerebral ischemia［J］.Exp Neurobiol,2017,26(6):380-389.

［15］Zhao GA, Chen D, Ding MW. Effects of breviscapine combined with preconditioning on myocardial protection in rabbits with ischemia reperfusion［J］. Journal of Clinical Cardiology, 2009,25(2):135-136.(in Chinese)

赵国安,陈丹,丁明伟.灯盏花素联合预适应对家兔缺血再灌注心肌保护作用的影响［J］.临床心血管杂志, 2009,25（2）:135-136.

［16］Huang ZhJ, He ShA, Lei B. Clinical analysis of acute cerebral infarction by Dengzhanhua injection and Xiongqin injection combined with Xuesaitong treatment ［J］. Journal of Chinese Medicinal Material, 2014,37(6):1093-1095. (in Chinese)

黄振坚，何世安，雷斌. 灯盏花、芎嗪注射液联合血塞通治疗急性脑梗死的临床分析［J］. 中药材，2014，37（6）：1093-1095.

［17］Chen XM, Chen HS, Xu MJ, et al. Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury［J］. Acta Pharmacol Sin, 2013,34(1): 71-75.

［18］Yan C, Zhang J, Wang S, et al. Neuroprotective effects of rutaecarpine on cerebral ischemia reperfusion injury［J］. Neural Regen Res, 2013,8(22): 2035-2038.

［19］Lou XY, Cheng JL, Zhang B. Therapeutic effect and mechanism of breviscapine on cisplatin-induced nephrotoxicity in mice［J］. Asian Pac J Trop Med, 2015, 8(10):873-875.

［20］Sun K, Fan JY, Han JY. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculato disturbances and neuron damage［J］. Acta Pharm Sin B, 2015,5(1): 12-20.

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