灯盏花素抗大鼠脑缺血再灌注损伤的作用研究
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摘要
目的在缺血再灌注脑损伤大鼠模型中观察灯盏花素对脑组织游离脂肪酸的作用,探索其作用机制。方法采用大脑中动脉线栓法阻断SD大鼠大脑中动脉2 h,再灌注24 h,建立大鼠局灶性脑缺血再灌注模型,于线栓后5 min尾静脉注射灯盏花素注射液,期间进行局部脑血流量监测。再灌注24 h后进行行为学和脑梗死体积的测定,并采用HPLC测定损伤侧脑组织中游离脂肪酸的含量。结果研究结果表明,与模型组相比,灯盏花素对急性缺血再灌注脑损伤具有明显的保护作用,呈剂量依赖性的减少脑梗死体积,在剂量为50 mg·kg-1时差异具有统计学意义;且在缺血后5 min给予50 mg·kg-1的灯盏花素后,能升高改善缺血90 min至再灌(缺血120 min)期间的脑血流量。模型组大鼠脑组织中n6多不饱和脂肪酸亚油酸(C18:2)和花生四稀酸(C20:4)的含量较假手术组明显升高,给予灯盏花素后,n6多不饱和脂肪酸C18:2和C20:4含量水平均较模型组显著降低。结论研究结果提示灯盏花素可能通过改善脑血流量和抑制脑组织n6多不饱脂肪酸的含量发挥抗脑缺血作用。
Objective To determine the effect and mechanism of breviscapine on free fatty acids in the rat brain model of ischemia-reperfusion. Methods The ischemic model was produced by occluding the middle cerebral artery for 2 hours and reperfusing for 24 hours. The rat model was injected breviscapine via tail vein5 min after the suture, and the regional cerebral blood flow was monitored. After the 24 hour reperfusion, the behavioral and cerebral infarction volumes were measured. The content of free fatty acids in the injured brain tissue was determined by HPLC. Results Breviscapine apparently protected against retinal ischemic injury and decreased the infarct volume in a dose-dependent manner. Significant difference was observed after treatment with breviscapine(50 mg·kg-1). When treating with 50 mg·kg-1 breviscapine 5 min after the ischemia,the cerebral blood flow was improved from 90 min to 120 min after the ischemia. Compar ed with the sham operation group, the levels of linoleic acid and arachidonic acid in the brain tissue of the model group were obviously elevated, but the levels in the model group were reduced after breviscapine treatment. Conclusion The protective action of breviscapine against cerebral ischemia injury may be via improving cerebral blood flow and decreasing the content of n6 polyunsaturated fatty acids in the brain tissue.
Objective To determine the effect and mechanism of breviscapine on free fatty acids in the rat brain model of ischemia-reperfusion. Methods The ischemic model was produced by occluding the middle cerebral artery for 2 hours and reperfusing for 24 hours. The rat model was injected breviscapine via tail vein5 min after the suture, and the regional cerebral blood flow was monitored. After the 24 hour reperfusion, the behavioral and cerebral infarction volumes were measured. The content of free fatty acids in the injured brain tissue was determined by HPLC. Results Breviscapine apparently protected against retinal ischemic injury and decreased the infarct volume in a dose-dependent manner. Significant difference was observed after treatment with breviscapine(50 mg·kg-1). When treating with 50 mg·kg-1 breviscapine 5 min after the ischemia,the cerebral blood flow was improved from 90 min to 120 min after the ischemia. Compar ed with the sham operation group, the levels of linoleic acid and arachidonic acid in the brain tissue of the model group were obviously elevated, but the levels in the model group were reduced after breviscapine treatment. Conclusion The protective action of breviscapine against cerebral ischemia injury may be via improving cerebral blood flow and decreasing the content of n6 polyunsaturated fatty acids in the brain tissue.
引文
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[16]Sabogal-Guáqueta AM,Posada-Duque R,Cortes NC,et al. Changes in the hippocampal and peripheral phospholipid profiles are associated with neurodegeneration hallmarks in a long-term global cerebral ischemia model:Attenuation by Linalool[J]. Neuropharmacology,2018,135:555-571.
[17]Bonventre JV. Roles of phospholipases A2 in brain cell and tissue injury associated with ischemia and excitotoxicity[J].J Lipid Mediat Cell Signal,1997,16(3):199-208.
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[22]SakaiM,KakutaniS,TokudaH,etal. Arachidonic acid and cerebral ischemia risk:a systematic review of observational studies[J]. Cerebrovasc Dis,2014,4(3):198-211.
[2]Bonventre JV,Huang Z,Taheri MR,et al. Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2[J]. Nature,1997,390(6660):622-625.
[3]BradyKM,TexelSJ,KishimotoK,etal.Cytosolic phospholipase A2 alpha modulates NMDA neurotoxicity in mouse hippocampal cultures[J]. Eur J Neurosci,2006,24(12):3381-3386.
[4]Ward NC,Croft KD,Blacker D,et al. Cytochrome P450metabolites of arachidonic acid are elevated in stroke patients compared with healthy controls[J]. Clin Sci,2011,121(11):501-507.
[5]李慧,姜亚芳.脑卒中患者早期康复护理干预措施的研究进展[J].中华护理杂志,2010,45(2):187-189.
[6]刘珍君,严江涛,王宏伟,等.脑卒中与血浆促酰化蛋白、游离脂肪酸和脂联素水平的关系及意义[J].中华神经科杂志,2004,37(6):549-551.
[7]杨淑艳,钟秀宏,张以忠,等.灯盏花素药理作用研究进展[J].吉林医药学院学报,2008,29(6):360-363.
[8]陈康宁,董为伟.灯盏花注射液对脑缺血损伤的防治研究[J].中国中西医结合杂志,1998,18(11):684-686.
[9]徐淑云.药理学实验方法[M]. 3版.中国医药科技出版社,2012:p1066-1067.
[10] Mehta A,Oeser AM,Carlson MG. Rapid quantitation of free fatty acids in human plasma by high-performance liquid chromatography[J]. J Chromatogr B Biomed Sci Appl,1998,719(1-2):9-23.
[11] Shen F,Qi J,Xu F,et al. Age-related distributions of nine fasting plasma free fatty acids in a population of Chinese adults[J]. Clinica Chimica Acta,2013,415:81-87.
[12]Bonita R,Mendis S,Truelsen T,et al. The global stroke initiative[J]. Lancet Neurol,2004,3(7):391-393.
[13]刘红梅,高天明.急性脑缺血动物模型实验研究进展[J].南方医科大学学报,1999,19(4):368-370.
[14]Ebbert J,Jensen M. Fat depots,free fatty acids,and dyslipidemia[J]. Nutrients,2013,5(2):498-508.
[15]Gasparovic C,Rosenberg GA,Wallace JA,et al. Magnetic resonance lipid signals in rat brain after experimental stroke correlate with neutral lipid accumulation[J]. Neurosci Lett,2001,301(2):87-90.
[16]Sabogal-Guáqueta AM,Posada-Duque R,Cortes NC,et al. Changes in the hippocampal and peripheral phospholipid profiles are associated with neurodegeneration hallmarks in a long-term global cerebral ischemia model:Attenuation by Linalool[J]. Neuropharmacology,2018,135:555-571.
[17]Bonventre JV. Roles of phospholipases A2 in brain cell and tissue injury associated with ischemia and excitotoxicity[J].J Lipid Mediat Cell Signal,1997,16(3):199-208.
[18]Zhang J,Barasch N,Li RC,et al. Inhibition of cytosolic phospholipase A2 alpha protects against focal ischemic brain damage in mice[J]. Brain Res,2012,1471:129-137.
[19] Menschikowski M,Hagelgans A,Siegert G. Secretory phospholipase A2 of groupⅡA:is it an offensive or a defensive player during atherosclerosis and other inflammatory diseases?[J]. Prostag Oth Lipid Med,2006,79(1-2):1-33.
[20]Bosetti F,Weerasinghe GR. The expression of brain cyclooxygenase-2 is down-regulated in the cytosolic phospholipase A2 knockout mouse[J]. J Neurochem,2003,87(6):1471-1477.
[21]Sapirstein A,Saito H,Texel S,et al. Cytosolic phospholipase A2αregulates induction of brain cyclooxygenase-2in a mouse model of inflammation[J]. Am J Physiol Regul Integr Comp Physiol,2005,288(6):1774-1782.
[22]SakaiM,KakutaniS,TokudaH,etal. Arachidonic acid and cerebral ischemia risk:a systematic review of observational studies[J]. Cerebrovasc Dis,2014,4(3):198-211.