中药脑必通在大鼠大脑中动脉梗死模型中的脑保护机制

中药脑必通在大鼠大脑中动脉梗死模型中的脑保护机制

卢国宝, 黄晚慧, 罗丽珊, 王红, 陈光发, 周文轩, 朱依谆^*

1. 新加坡国立大学医学院药理学系, 新加坡
2. 香港保健协会, 香港
3. 复旦大学药学院药理学系, 上海 200032

收稿日期:2009-04-27 修回日期:2009-05-10 出版日期:2009-06-15 发布日期:2009-06-15
通讯作者: 朱依谆*

Mechanisms of cerebral protection of Chinese herbal extract-Braintone on middle cerebral artery occluded rats

Kok-Poh Loh, Wan-Hui Wong, Li-Shan Low, Hong Wang, Benny Kwong-Huat Tan, Vincent Chou, Yi-Zhun Zhu^*

1. Department of Pharmacology, National University of Singapore, Singapore
2. Hong Kong Health Care Association Ltd., Hong Kong
3. Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China

Received:2009-04-27 Revised:2009-05-10 Online:2009-06-15 Published:2009-06-15
Contact: Yi-Zhun Zhu*

摘要/Abstract

摘要： 自由基导致的神经细胞损伤是中风发病机理之一。多项体外和体内研究证明, 通过干预自由基在局部缺血部位导致的细胞凋亡, 抗氧化剂可起到神经保护作用, 而具有抗氧化功效的自然产品无疑是一种极有潜力的治疗中风的候选药物。本研究的目的是评估脑必通 (Braintone) 在Wistar大鼠大脑中动脉梗死模型 (MCAO) 的治疗作用。与对照组相比, 脑必通治疗组大鼠促凋亡基因 (AT2受体, FAS, BAX和BCL-XS)的表达量显著地减少(分别是0.4-, 0.72-, 0.76-, 0.32倍, P<0.05)。免疫组化结果显示这些基因所对应的蛋白质表达量也大量减少。TUNEL的观察结果进一步验证了脑必通的抗凋亡作用, 从而证明脑必通作为一种抗氧化药物, 对中风的治疗的确具有一定的潜在功效。

关键词: 中风, 大脑中动脉梗死模型, 脑必通, 抗氧化剂, 氧化应激

Abstract:

Free radical induced neuronal damage is involved in stroke. Several in vitro and in vivo studies have proved that antioxidant could act as neuroprotective agent through intervening with free-radical mediated apoptosis in the ischemic penumbra. In particular, natural products which contain antioxidant properties have undoubtedly potential for stroke treatment. In the present study, therapeutic effects of Braintone on Wistar rats undergone middle cerebral artery occlusion (MCAO) was evaluated. Gene expression levels of pro-apoptotic genes (AT2 receptor, FAS, BAX and BCL-XS) were showed to be significantly reduced in Braintone treated groups (0.4-, 0.72-, 0.76-, 0.32-fold, P<0.05) as compared to vehicle group. Significant reduction of immunoreactivity of protein production of these genes, together with least nuclear green fluorescence observed in TUNEL, Braintone as an antioxidant drug, is concluded to have promising therapeutic effect for stroke treatment.

Key words: Stroke, Stroke, MCAO, MCAO, Braintone, Braintone, Antioxidant, Antioxidant, Oxidative stress, Oxidative stress

中图分类号:

R285

Supporting:

Foundation items: National Medical Research Council of Singapore (R-184-000-037-213 and R-184-000-109-213).
^*Corresponding author. Tel.: 86-21-54237077; fax: 86-21-64042268;
e-mail: zhuyz@fudan.edu.cn; phczhuyz@nus.edu.sg

卢国宝, 黄晚慧, 罗丽珊, 王红, 陈光发, 周文轩, 朱依谆^*. 中药脑必通在大鼠大脑中动脉梗死模型中的脑保护机制[J]. .

Kok-Poh Loh, Wan-Hui Wong, Li-Shan Low, Hong Wang, Benny Kwong-Huat Tan, Vincent Chou, Yi-Zhun Zhu^*. Mechanisms of cerebral protection of Chinese herbal extract-Braintone on middle cerebral artery occluded rats [J]. .

参考文献

[1] Zemke, D.; Smith, J.; Reeves, M.J.; Majid, A. Neurotoxicology. 2004, 25, 895-904.
[2] Zhu, Y.Z.; Huang, S.H.; Tan, B.K.H.; Sun, J.; Whiteman, M.; Zhu, Y.C. Nat. Prod. Rep. 2004, 21, 478-489.
[3] Thorne Research, Rhodiola Rosea. Altern. Med. Rev. 2002, 7, 421-423.
[4] Lu, Q.; Zhu, Y.Z.; Wong, P.T.H. Neuroreport. 2005, 16, 1963-1967.
[5] Zhu, Y.Z.; Chong, C.L.; Chuah, S.C.; Huang, S.H.; Nai, H.S.; Tong, H.T.; Whiteman, M.; Moore, P.K. Am. J. Physiol. Heart Circ. Physiol. 2006, 290, 517-524.
[6] Zhu, Y.Z.; Chimon, G.N.; Zhu, Y.C.; Lu, Q.; Li, B.; Hu, H.A.; Yap, E.H.; Lee, H.S.; Wong, P.T.H. Neuroreport. 2000, 11, 1191-1194.
[7] Kagiyama, T.; Kagiyama, S.; Philips, M.I. Regul. Peptide. 2003, 110, 241-247.
[8] Mehmet, H. Cell Death Differ. 2001, 8, 659-661.
[9] Akhtar, R.S.; Ness, J.M.; Roth, K.A. Biochim. Biophys. Acta. 2004, 1644, 189-203.
[10] Wiessner, C.; Allegrini, P.R.; Rupalla, K.; Sauer, D.; Oltersdorf, T.; McGregor, A.L.; Bischoff, S.; Bottiger, B.W.; van der, Putten, H. Neurosci. Lett. 1999, 268, 119-122.
[11] Ferrer, I.; Friguls, B.; Dalfo, E; Justicia, C.; Planas, A.M. Neuropathol. Appl. Neurobiol. 2003, 29, 472-481.
[12] Gupta, R.; Singh, M.; Sharma, A. Pharmacol. Res. 2003, 48, 209-215.
[13] Low, L.; Wong, W.; Duan, W.; Zhou, S.; Chou, V.; Zhu, Y.Z. The prophylaxtic effects of Chinese herbal extract ‘Braintone’ on stroked Wistar rats. In: Zhu, Y.Z.; Tan B.K.; Bay, B.H. and Liu, C.H. eds. Natural products: a must for human survive. London: World Scientific Press, 2006, 380-392.
[14] Loh, K.P.; Huang, S.H.; De Silva, R.; Tan, B.K.; Zhu, Y.Z. Curr. Alzheimer Res. 2006, 3, 327-337.
[15] Chandra, J.; Samali, A.; Orrenius, S. Free Radic. Biol. Med. 2000, 29, 323-333.
[16] Loh, K.P.; Low, L.S.; Wong, W.H.; Zhou, S.; Chou, W.H.; Zhu, Y.Z. Neurosci. Lett. 2006, 19, 28-33.