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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (4): 26-30.doi: 10.6040/j.issn.1671-7554.0.2014.773

• 基础医学 • 上一篇    下一篇

超时间窗溶栓治疗对大鼠急性脑梗死后自由基活性和Caspase-3表达的影响

刘杰, 刘金之, 林艳, 黄占, 王爱华   

  1. 山东大学附属千佛山医院神经内科, 山东 济南 250014
  • 收稿日期:2014-10-31 修回日期:2015-01-28 出版日期:2015-04-10 发布日期:2015-04-10
  • 通讯作者: 王爱华.E-mail:wangah-0052@sina.com E-mail:wangah-0052@sina.com
  • 基金资助:
    山东省科技发展计划(2011GGB14095)

Effects of thrombolytic therapy with broadened therapeutic window on the free radical activity and the expression of Caspase-3 in a rat model of acute cerebral infarction

LIU Jie, LIU Jinzhi, LIN Yan, HUANG Zhan, WANG Aihua   

  1. Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China
  • Received:2014-10-31 Revised:2015-01-28 Online:2015-04-10 Published:2015-04-10

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摘要： 目的 研究急性脑梗死超时间窗溶栓治疗对大鼠脑组织一氧化氮(NO)、一氧化氮合酶(NOS)、丙二醛(MDA)、超氧化物歧化酶(SOD)的活性及Caspase-3表达的影响.方法 采用大鼠自体血栓制作大脑中动脉梗死模型,将144只SD大鼠随机分为对照组、梗死组、6 h溶栓组,各48只.采用比色法和羟胺法分别检测梗死脑组织中NO、MDA含量,NOS、SOD活性;采用HE染色观察神经元形态变化;采用免疫组化法检测脑组织神经元型一氧化氮合酶(nNOS)和Caspase-3的表达.结果 与梗死组相比,6 h溶栓组NO、MDA含量、诱导型一氧化氮合酶(iNOS)活性在各时间点均明显降低(P <0.05),SOD活性升高(P <0.05),nNOS、Caspase-3的表达明显减少(P <0.05).结论 超时间窗溶栓治疗可通过降低自由基活性,增加SOD活性,减轻梗死后氧化应激反应,减少凋亡分子的表达.

关键词: 脑梗死, 一氧化氮合酶, 子宫肌腺症, 病理检查, 超时间窗, 溶栓, Caspase-3, B超

Abstract: Objective To explore the effects of thrombolytic therapy with broadened therapeutic window on nitric oxide (NO), nitric-oxide synthase (NOS), malondialdehude (MDA), superoxide dismutase (SOD) and Caspase-3 in rats with acute cerebral infarction. Methods Rat models of middle cerebral artery occlusion (MCAO) were established with autologous thrombus. A total of 144 SD rats were randomly divided into control group, stroke group, and 6 h thrombolytic group (n=48 in each group). The contents of NO, NOS, MDA and SOD of cerebral tissue were assayed by the colorimetric and hydroxylamine methods. Changes of neurons were observed by HE staining. Expressions of neuronal NOS (nNOS) and Caspase-3 were determined by immunohistochemical techniques. Results Compared with stroke group, the contents of NO, inducible NOS (iNOS), MDA of 6 h thrombolytic group obviously decreased at different time points (P <0.05), the activity of SOD obviously increased (P< 0.05), neurons in the cortical brain increased, the expression of nNOS and Caspase-3 obviously decreased (P <0.05). Conclusion Thrombolytic therapy with broadened therapeutic window can decrease the reaction of oxidative stress and the expression of the apoptosis.

Key words: Cerebral infarction, Nitric-oxide synthase, Caspase-3, Thrombolysis, Time window

中图分类号: 

  • R743.3
[1] The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke[J]. N Engl J Med, 1995, 333(24):1581-1587.
[2] Balami JS, Hadley G, Sutherland BA,et al. The exact science of stroke thrombolysis and the quiet art of patient selection[J]. Brain, 2013(pt12), 136:3528-3553.
[3] Ogata T, Christensen S, Nagakane Y, et al. The effects of alteplase 3 to 6 hours after stroke in the EPITHET-DEFUSE combined dataset: post hoc case-control study[J]. Stroke, 2013, 44(1): 87-93.
[4] Bai Q, Zhao Z, Sui H, et al. Comparison of fast MRI-based individual thrombolysis therapy for patients with superacute infarction[J]. J Stroke Cerebrovasc Dis, 2014, 23(4): e263-269. doi:10.1016/j.jstrokecerebrovasdis.2013.11.014.
[5] 林艳,刘金之,刘杰,等. 超时间窗溶栓治疗对急性脑梗死体积、微血管密度及黏附因子表达的影响[J]. 山东大学学报:医学版,2014,52(5): 20-24. LIN Yan, LIU Jinzhi, LIU Jie, et al. Effect of thrombolytic therapy with broadened therapeutic window on infarct volume, microvessel density and adherence factors in acute cerebral infarction[J]. Jounal of Shandong University: Health Sciences, 2014, 52(5):20-24.
[6] Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke[J]. Int J Stroke, 2009, 6(4):461-470.
[7] Chauhan A, Sharma U, Jagannathan NR, et al. Rapamycin protects against middle cerebral artery occlusion induced focal cerebral ischemia in rats[J]. Behav Brain Res, 2011, 225(2):603-609.
[8] Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage[J]. Neuropharmacology, 2008, 55(3):310-318.
[9] Heeba GH, El-Hanafy AA. Nebivolol regulates eNOS and iNOS expressions and alleviates oxidative stress in cerebral ischemia/reperfusion injury in rats[J]. Life Sci, 2012, 90(11-12):388-395.
[10] Liu DH, Yuan FG, Hu SQ, et al. Endogenous nitric oxide induces activation of apoptosis signal-regulating kinase 1 via S-nitrosylation in rat hippocampus during cerebral ischemia-reperfusion[J]. Neuroscience, 2013, 229:36-48.
[11] Donnan GA, Davis SM. IST-3: a major contribution to thrombolysis research[J]. Int J Stroke, 2012, 7(7):566-567.
[12] Donnan GA, Davis SM. Stroke: Expanded indications for stroke thrombolysis—what next?[J]. Nat Rev Neurol, 2012, 8(9):482-483.
[13] Choi-Kwon S, Park KA, Lee HJ, et al. Temporal changes in cerebral antioxidant enzyme activities after ischemia and reperfusion in a rat focal brain ischemia model: effect of dietary fish oil[J]. Brain Res Dev Brain Res, 2004, 152(1): 11-18.
[14] Irmak MK, Fadillioglu E, Sogut S, et al. Effects of caffeic acid phenethyl ester and alpha-tocopherol on reperfusion injury in rat brain[J]. Cell Biochem Funct, 2003, 21(3): 283-289.
[15] He S, Yang J, Wu B, et al. Neuroprotective effect of parthenocissin A, a natural antioxidant and free radical scavenger, in focal cerebral ischemia of rats[J]. Phytother Res, 2010, 24(Suppl 1):S63-70.
[16] Gaur V, Aggarwal A, Kumar A. Protective effect of naringin against ischemic reperfusion cerebral injury: possible neurobehavioral, biochemical and cellular alterations in rat brain[J]. Eur J Pharmacol, 2009, 616(1-3):147-154.
[17] Goto K, Ishige A, Sekiguchi K, et al. Effects of cycloheximide on delayed neuronal death in rat hippocampus[J]. Brain Res, 1990, 534(1-2):299-302.
[18] Broughton BR, Reutens DC and Sobey CG. Apoptotic mechanisms after cerebral ischemia[J]. Stroke, 2009, 40(5):e331-339. doi:10.1161/STROKEAHA.531632.
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