MC-002对大鼠局灶性脑缺血/再灌注治疗时间窗的研究

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (8): 867-873.

MC-002对大鼠局灶性脑缺血/再灌注治疗时间窗的研究

曾胜男¹, 何广卫³, 吴强³, 袁晓艳⁴, 吴玉林²

¹湖南省邵东县中医院药剂科,邵阳 422800,湖南;
²中国药科大学生理教研室,南京 210009,江苏;
³合肥医工医药有限公司暨安徽省药物再创新工程技术研究中心,合肥 230088, 安徽;
⁴中南大学湘雅医院神经外科, 长沙 410000, 湖南

收稿日期:2010-11-04 修回日期:2011-04-18 出版日期:2011-08-26 发布日期:2011-09-07
通讯作者: 吴玉林,男,博士,副教授,硕士生导师,研究方向:心血管药理学。Tel: 025-8532087 E-mail: wylcpu@yahoo.com.cn
作者简介:曾胜男,女,硕士,研究方向:心血管药理学。E-mail: hnzsn078@126.com
基金资助:
十一五重大专项课题号(2009ZX09103-123)

Therapeutic time window of MC-002 on focal cerebral ischemia-reperfusion rats

ZENG Sheng-nan¹, HE Guang-wei³, WU Qiang³, YUAN Xiao-yan⁴, WU Yu-lin²

¹Department of Physiology, Chinese Medicine Hospital of Shaodong Count, Shaoyang 422800, Hunan, China;
²Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China;
³Hefei Industrial Pharmaceutical Insitute CO.Ltd. Anhui Research Center of Pharmaceutical Removation, Hefei 230088, Anhui, China;
⁴Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410000, Hunan, China

Received:2010-11-04 Revised:2011-04-18 Online:2011-08-26 Published:2011-09-07

摘要/Abstract

摘要： 目的: 研究受试药3-甲氧基－4-O-(2'-亚甲基-3'5'6'-三甲基吡嗪基)肉桂酸(MC-002)对大鼠局灶性脑缺血/再灌注损伤(CIRI)的治疗时间窗。方法: 线栓法制作大鼠大脑中动脉闭塞(MCAO)2 h/再灌注 22 h,并于复灌后0、 0.5、 1、 2、 4 h 时治疗给药。观察MC-002对CIRI大鼠脑功能、脑梗死体积、脑含水量、组织形态学的影响以及MC-002各剂量组对大鼠脑组织内生化指标的影响。结果: MC-002在复灌后0、 0.5、 1、 2 h 给药能够显著性改善MCAO后大鼠的脑神经功能(P<0.05,P<0.01),降低大鼠的脑梗死率和含水量(P<0.05、P<0.01);增加CIRI大鼠脑组织超氧化物歧化酶(SOD)活力(P<0.01),降低丙二醛(MDA)及乳酸(LD)含量(P<0.05, P<0.01)。脑组织病理切片结果显示,和模型组比较,治疗组神经细胞形态和数目均得到显著改善。结论: MC-002 2 h 内治疗给药对大鼠局灶性脑缺血/再灌注损伤有很好的保护作用。

关键词: MC-002, 局灶性脑缺血/再灌注, 治疗时间窗

Abstract: AIM: To investigate therapeutic time window of MC-002 on the focal cerebral ischemia-reperfusion rats.METHODS: The models with cerebral ischemicre-reperfusion were induced by intraluminal middle cerebral artery occlusion (MCAO) with a nylon monofilament suture, 2 h occlusion followed by 22 h reperfusion. Therapeutic medicine was intravenously administered after reperfusion for 0, 0.5, 1, 2, 4 h. The effect of MC-002 at different doses on neurological scores, infarct sizes, water contents, pathological changes and the biochemical indexes of CIRI rats were examined.RESULTS: MC-002 administered at 0, 0.5, 1, 2 h after reperfusion significantly improved the CIRI rats' neurological function and reduced the cerebral infarct size and edema; The content of MDA and LD in brain were markedly decreased (P<0.05 and P<0.01), and the activity of SOD was significantly enhanced (P<0.01). The pathological observations showed that neuronal cells shape and number were obviously improved after treated with MC-002 compared with model groups.CONCLUSION: The results showed that the therapeutic time window of MC-002 extended for up to 2 h after CIRI.

Key words: MC-002, Focal cerebral ischemiareperfusion, Therapeutic time window

中图分类号:

R965.2

曾胜男, 何广卫, 吴强, 袁晓艳, 吴玉林. MC-002对大鼠局灶性脑缺血/再灌注治疗时间窗的研究[J]. 中国临床药理学与治疗学, 2011, 16(8): 867-873.

ZENG Sheng-nan, HE Guang-wei, WU Qiang, YUAN Xiao-yan, WU Yu-lin. Therapeutic time window of MC-002 on focal cerebral ischemia-reperfusion rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(8): 867-873.

参考文献

[1] Mehta SL, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics[J]. Brain Res Rev, 2007, 54(1): 34-66.
[2] Kao TK, Ou YC, Kuo JS, et al. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats[J]. Neurochem Int, 2006, 48(3): 166-176.
[3] Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-91.
[4] Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination[J]. Stroke, 1986, 17(3):472-476.
[5] 朱萧玲, 熊利泽, 陈绍洋, 等. 川芎嗪注射液治疗大鼠脑缺血/再灌注损伤的时间窗[J]. 中华神经外科疾病研究杂志, 2006, 5(4): 334-337.
[6] Jia J, Zhang X, Hu YS, et al. Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: Therapeutic time window and its mechanism[J]. Thromb Res, 2009, 123(5): 727-730.
[7] Babu CS, Ramanathan M. Pre-ischemic treatment with memantine reversed the neurochemical and behavioural parameters but not energy metabolites in middle cerebral artery occluded rats[J]. Pharmacol Biochem Behav, 2009, 92(3):424-432.
[8] López-Sánchez C, Martín-Romero FJ, Sun F, et al. Blood micromolar concentrations of kaempferol afford protection against ischemia/reperfusion-induced damage in rat brain[J]. Brain Res, 2007, 1182:123-137.
[9] Durukan A, Tatlisumak T. Acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia[J]. Pharmacol Biochem Behav, 2007, 87(1):179-197.
[10] 王姗, 李家明, 何广卫, 等. MC-001对大鼠脑缺血-再灌注损伤的保护作用及机制[J]. 中国临床药理学与治疗学, 2008, 13(11):59-63.
[11] 李茜, 王秋娟, 郭青龙. 新型神经保护剂TQ0701-2对大鼠脑缺血再灌注损伤的保护作用[J]. 中国临床药理学与治疗学, 2010, 15(1):43-47.
[12] Ayata C, Ropper AH. Ischaemic brain oedema[J]. J Clin Neurosci, 2002, 9(2):113-124.
[13] Sugawara T, Jadhav V, Ayer R, et al. Thrombin inhibition by argatroban ameliorates early brain injury and improves neurological outcomes after experimental subarachnoid hemorrhage in rats[J]. Stroke, 2009, 40(4):1530-1532.
[14] Nagel S, Su Y, Horstmann S, et al. Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat-Effects on BBB breakdown and MMP expression in the acute and subacute phase[J]. Brain Res, 2008, 1188:198-206.