姜黄素对脑缺血再灌注损伤的保护作用机制研究进展

doi:10.12092/j.issn.1009-2501.2019.11.015

摘要/Abstract

摘要：

缺血性卒中是全球死亡和致残的主要原因，恢复脑组织的血流量（再灌注）是目前最有效的治疗方法。然而，再灌注后，脑组织中过量活性氧的产生，炎症细胞异常募集，炎症因子过量释放，细胞自噬，线粒体功能障碍，钙稳态失调，内质网应激，谷氨酸兴奋性毒性，细胞凋亡及血脑屏障破坏等病理机制会进一步加重细胞损伤和死亡，最终影响神经功能恢复。大量的研究表明姜黄素可通过抑制脑缺血再灌注损伤的多种病理机制而发挥显著神经保护作用，最终改善脑循环，减少梗死体积，减少脑水肿，促进血脑屏障修复，改善神经功能。因此，姜黄素可通过减轻脑缺血再灌注损伤而改善神经功能，具有补充现有缺血性卒中治疗方法的潜力。

关键词: 姜黄素, 脑缺血再灌注损伤, 神经保护

Abstract:

Ischemic stroke is a major cause of death and disability in the world. Currently, the most effective treatment for ischemic stroke is to prevent ischemia and hypoxia injury and repair damaged tissues by restoring blood flow (reperfusion). Although reperfusion is a signal for the termination of ischemia and hypoxia, it may subsequently increase cell damage and death through excessive production of reactive oxygen species, abnormal recruitment of inflammatory cells, and excessive release of inflammatory factors, autophagy, mitochondrial dysfunction, calcium homeostasis disorder, endoplasmic reticulum stress, glutamate excitotoxicity, apoptosis, destruction of blood-brain barrier and other mechanisms. A large number of studies have shown that curcumin can play a significant neuroprotective effect by slowing down various pathological mechanisms of ischemia-reperfusion injury, and ultimately improving cerebral circulation, reducing infarct volume, reducing cerebral edema, promoting blood-brain barrier repair, and improving neurological function. Therefore, curcumin can improve neurological function by alleviating ischemia-reperfusion injury, and has the potential to supplement the existing treatment methods for ischemic stroke.

Key words: curcumin, cerebral ischemia-reperfusion injury, neuroprotection

中图分类号:

R741

刘小艳，田野，刘骥飞，苏刚，张振昶. 姜黄素对脑缺血再灌注损伤的保护作用机制研究进展[J]. 中国临床药理学与治疗学, 2019, 24(11): 1305-1309.

LIU Xiaoyan, TIAN Ye, LIU Jifei, SU Gang, ZHANG Zhenchang. Research progress on the protective mechanisms of curcumin on cerebral ischemia-reperfusion injury[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(11): 1305-1309.

参考文献

［1］Hankey GJ. Stroke［J］. Lancet, 2017, 389(10069): 641-654.
［2］Feigin VL, Norrving B, Mensah GA. Global Burden of Stroke ［J］. Circ Res, 2017,120(3): 439-448.
［3］Guzik A, Bushnell C. Stroke epidemiology and risk factor management ［J］. Continuum (Minneap Minn), 2017, 23(1, Cerebrovascular Disease): 15-39.
［4］Li P, Stetler RA, Leak RK, et al. Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to repair the genome and improve stroke recovery ［J］. Neuropharmacol, 2018,134(Pt B): 208-217.
［5］Enzmann G, Kargaran S, Engelhardt B. Ischemia-reperfusion injury in stroke: impact of the brain barriers and brain immune privilege on neutrophil function ［J］. Ther Adv Neurol Disord, 2018, 11: 1756286418794184.
［6］Huang L, Chen C, Zhang X, et al. Neuroprotective effect of curcumin against cerebral ischemia-reperfusion via mediating autophagy and inflammation ［J］. J Mol Neurosci, 2018, 64(1): 129-139.
［7］Liu L, Zhang W, Wang L, et al. Curcumin prevents cerebral ischemia reperfusion injury via increase of mitochondrial biogenesis ［J］. Neurochem Res, 2014, 39(7): 1322-1331.
［8］Bavarsad K, Barreto GE, Hadjzadeh MA, et al. Protective effects of curcumin against ischemia-reperfusion injury in the nervous system ［J］. Mol Neurobiol, 2019, 56(2): 1391-1404.
［9］Yavarpour-Bali H, Ghasemi-Kasman M, Pirzadeh M. Curcumin-loaded nanoparticles: a novel therapeutic strategy in treatment of central nervous system disorders ［J］. Int J Nanomedicine, 2019, 14: 4449-4460.
［10］Chen HT, Fan YL, Fang H, et al. Curcumin alleviates ischemia reperfusion-induced late kidney fibrosis through the APPL1/Akt signaling pathway ［J］. J Cell Physiol, 2018, 233(11): 8588-8596.
［11］Salim S. Oxidative stress and the central nervous system ［J］. J Pharmacol Exp Ther, 2017, 360(1): 201-205.
［12］Radak D, Resanovic I, Isenovic ER. Link between oxidative stress and acute brain ischemia ［J］. Angiology, 2014, 65(8): 667-676.
［13］Altinay S, Cabalar M, Isler C, et al. Is chronic curcumin supplementation neuroprotective against ischemia for antioxidant activity, neurological deficit, or neuronal apoptosis in an experimental stroke model ［J］ ? Turk Neurosurg, 2017, 27(4): 537-545.
［14］Ahmad N, Umar S, Ashafaq M, et al. A comparative study of PNIPAM nanoparticles of curcumin, demethoxycurcumin, and bisdemethoxycurcumin and their effects on oxidative stress markers in experimental stroke ［J］. Protoplasma, 2013, 250(6): 1327-1338.
［15］Mukherjee A, Sarkar S, Jana S, et al. Neuro-protective role of nanocapsulated curcumin against cerebral ischemia-reperfusion induced oxidative injury ［J］. Brain Res, 2019, 1704: 164-173.
［16］Wicha P, Tocharus J, Janyou A, et al. Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury, attenuates inflammation, and improves antioxidant defenses in a rat stroke model ［J］. PLoS One, 2017, 12(12): e0189211.
［17］Kakkar V, Muppu SK, Chopra K, et al. Curcumin loaded solid lipid nanoparticles: an efficient formulation approach for cerebral ischemic reperfusion injury in rats ［J］. Eur J Pharm Biopharm, 2013, 85(3 Pt A): 339-345.
［18］Dohare P, Garg P, Jain V, et al. Dose dependence and therapeutic window for the neuroprotective effects of curcumin in thromboembolic model of rat ［J］. Behav Brain Res, 2008, 193(2): 289-297.
［19］Jia G, Tan B, Ma J, et al. Prdx6 upregulation by curcumin attenuates ischemic oxidative damage via SP1 in rats after stroke ［J］. Biomed Res Int, 2017, 2017: 6597401.
［20］Wu JX, Zhang LY, Chen YL, et al. Curcumin pretreatment and post-treatment both improve the antioxidative ability of neurons with oxygen-glucose deprivation ［J］. Neural Regen Res, 2015, 10(3): 481-489.
［21］Li W, Suwanwela NC, Patumraj S. Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R ［J］. Microvasc Res, 2016, 106: 117-127.
［22］Amantea D, Russo R, Certo M, et al. Caspase-1-independent maturation of IL-1beta in ischemic brain injury: is there a role for gelatinases［J］? Mini Rev Med Chem, 2016, 16(9): 729-737.
［23］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.
［24］Lapchak PA. Neuroprotective and neurotrophic curcuminoids to treat stroke: a translational perspective ［J］. Expert Opin Investig Drugs, 2011,20(1): 13-22.
［25］Li W, Suwanwela NC, Patumraj S. Curcumin prevents reperfusion injury following ischemic stroke in rats via inhibition of NFkappaB, ICAM-1, MMP-9 and caspase-3 expression ［J］. Mol Med Rep, 2017,16(4): 4710-4720.
［26］Wang Y, Luo J, Li SY. Nano-curcumin simultaneously protects the blood-brain barrier and reduces M1 microglial activation during cerebral Ischemia-reperfusion injury ［J］. ACS Appl Mater Interfaces, 2019, 11(4): 3763-3770.
［27］Funk JL, Frye JB, Davis-Gorman G, et al. Curcuminoids limit neutrophil-mediated reperfusion injury in experimental stroke by targeting the endothelium ［J］. Microcirculation, 2013, 20(6): 544-554.
［28］Tu XK, Yang WZ, Chen JP, et al. Curcumin inhibits TLR2/4-NF-kappaB signaling pathway and attenuates brain damage in permanent focal cerebral ischemia in rats ［J］. Inflammation, 2014, 37(5): 1544-1551.
［29］Hou Y, Wang J, Feng J. The neuroprotective effects of curcumin are associated with the regulation of the reciprocal function between autophagy and HIF-1alpha in cerebral ischemia-reperfusion injury ［J］. Drug Des Devel Ther, 2019, 13: 1135-1144.
［30］Zhang Y, Fang M, Sun Y, et al. Curcumin attenuates cerebral ischemia injury in Sprague-Dawley rats and PC12 cells by suppressing overactivated autophagy ［J］. J Photochem Photobiol B, 2018, 184: 1-6.
［31］Tyagi N, Qipshidze N, Munjal C, et al. Tetrahydrocurcumin ameliorates homocysteinylated cytochrome-c mediated autophagy in hyperhomocysteinemia mice after cerebral ischemia ［J］. J Mol Neurosci, 2012, 47(1): 128-138.
［32］Liu F, Lu J, Manaenko A, et al. Mitochondria in Ischemic Stroke: New Insight and Implications ［J］. Aging Dis, 2018, 9(5): 924-937.
［33］Zhu H, Fan Y, Sun H, et al. Curcumin inhibits endoplasmic reticulum stress induced by cerebral ischemia-reperfusion injury in rats ［J］. Exp Ther Med, 2017, 14(5): 4047-4052.
［34］Li Y, Li J, Li S, et al. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK ［J］. Toxicol Appl Pharmacol, 2015, 286(1): 53-63.
［35］Gong L, Tang Y, An R, et al. RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways ［J］. Cell Death Dis, 2017, 8(10): e3080.
［36］Zhao J, Yu S, Zheng W, et al. Curcumin improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats ［J］. Neurochem Res, 2010, 35(3): 374-379.
［37］Lu Z, Liu Y, Shi Y, et al. Curcumin protects cortical neurons against oxygen and glucose deprivation/reoxygenation injury through flotillin-1 and extracellular signal-regulated kinase1/2 pathway ［J］. Biochem Biophys Res Commun, 2018, 496(2): 515-522.
［38］Xu L, Ding L, Su Y, et al. Neuroprotective effects of curcumin against rats with focal cerebral ischemia-reperfusion injury ［J］. Int J Mol Med, 2019, 43(4): 1879-1887.
［39］Yu L, Yi J, Ye G, et al. Effects of curcumin on levels of nitric oxide synthase and AQP-4 in a rat model of hypoxia-ischemic brain damage ［J］. Brain Res, 2012,1475: 88-95.
［40］Liu S, Cao Y, Qu M, et al. Curcumin protects against stroke and increases levels of Notch intracellular domain ［J］. Neurol Res, 2016, 38(6): 553-559.
［41］Shah FA, Gim SA, Sung JH, et al. Identification of proteins regulated by curcumin in cerebral ischemia ［J］. J Surg Res, 2016, 201(1): 141-148.

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