赤芍 801 对大鼠脑缺血/再灌注损伤后脑源性神经营养因子表达的影响

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (10): 1109-1115.

赤芍 801 对大鼠脑缺血/再灌注损伤后脑源性神经营养因子表达的影响

林敏, 林智颖, 陈晓春, 郑关毅, 黄俊山, 郑建明, 张静, 周宜灿

福建医科大学附属协和医院福建省老年医学研究所, 福州 350001, 福建

收稿日期:2008-05-22 修回日期:2008-07-02 出版日期:2008-10-26 发布日期:2020-10-19
通讯作者: 林智颖, 男, 博士生, 主治医师, 研究方向:神经变性疾病和脑血管病。Tel:0591-83357896 　E-mail:lzy8426@126.com
作者简介:林敏, 男, 硕士生, 研究方向:脑血管病。Tel:13405951838 　E-mail:linmin7920042005@21cn.com
基金资助:
福建省重大科技基金资助项目(2003 F009) ;福建医科大学青年教师科研基金(FJGXQ04021)

Effects of propyl gallate on BDNF expression after cerebral ischemia-reperfusion in rats

LIN Min, LIN Zhi-ying, CHEN Xiao-chun, ZHENG Guan-yi, HUANG Jun-shan, ZHENG Jian-ming, ZHANG Jing, ZHOU Yi-can

Fujian Institute of Geriatrics, the Affiliated Union Hospital of Fujian Medical University, Fuzhou350001, Fujian,China

Received:2008-05-22 Revised:2008-07-02 Online:2008-10-26 Published:2020-10-19

摘要/Abstract

摘要： 目的: 探讨赤芍 801 (propyl gallate, PG) 对大鼠局灶性脑缺血/再灌注损伤后神经功能损伤、细胞凋亡及脑源性神经营养因子(brain-derivedneurotrophic factor, BDNF) 表达的影响。方法: :线栓右侧大脑中动脉(middle cerebral artery,MCA) 制成SD 大鼠短暂局灶性脑缺血模型, 实验大鼠随机分成:正常对照组、假手术组、模型组、溶媒组、PG 组(分 PG 23.5、47、94 μmol/kg 3 个亚组) 等 5组。采用 Longa 等评分法进行大鼠神经功能评分;TUNEL 染色法观察缺血/再灌注不同时段(1、2、4、7 d) 模型鼠缺血区周边组织阳性神经元数量;免疫组织化学、蛋白免疫印迹法检测缺血/再灌注后不同时段各组缺血区周边组织 BDNF 的表达情况。结果: 脑缺血/再灌注后 1 d, 模型大鼠神经功能缺损评分、TUNEL 阳性细胞数均达到高峰。与此相仿, 该时段缺血周边区的 BDNF 表达亦达到高峰, 此后逐渐下降。该时段TUNEL 阳性细胞数和 BDNF 表达与其它各时段(2、4、7 d) 比较均有升高(P<0.01) 。予上述不同剂量组的 PG干预后, 47、94 μmol/kg 组大鼠的神经功能缺损评分、TUNEL 阳性细胞数均有明显下降, 同时缺血周边区的 BDNF 表达有明显增加;并以 94 μmol/kg组为著。结论: 脑缺血/再灌注后 BDNF 的早期表达增加可能对促进缺血周围区的损伤修复有重要作用;PG 能有效减轻脑缺血/再灌注损伤后神经细胞凋亡, 改善神经功能缺损症状, 机制可能与其促进 BDNF 的表达有关。

关键词: 赤芍 801, 脑缺血/再灌注, 脑源性神经营养因子, 神经元凋亡

Abstract: AIM: To explore the effect of propyl gallate on neurological dysfunction with injury after ce-rebral ischemia-reperfusion, and the effect on neuronal apoptosis and BDNF expression.METHODS: Middle cerebral artery occlusion models of rat transient focal ischemia were induced by inserting a filament through right internal carotid artery for 1 h .Rats were grouped as follows:control, sham operation, model, vehicle, PG 23.5 μmol/kg, PG 47 μmol/kg, PG 94 μmol/kg. Rats received intraperitoneal injections of PG immedi-ately after reperfusion, and the same volume physiolog-ical saline for vehicle group.Neuronogical behavior was evaluated by Longa's scoring method .Each rat re-ceived an injection every day and coronal brain sections were collected after l d, 2 d, 4 d, 7 d of reperfusion. Neuronal apoptosis in the boundary zone of the infarcts was evaluated by TUNEL staining .The expression of BDNF was investigated by immunohistochemistry and Western-blot with corresponding antibodies. RESULTS: Neurological deficits of model group and TUNEL positive neurons were observed at each time point and peaked at 1 d (P<0.01 compared to 2 d, 4 d, 7 d) .BDNF immunoreactivity increased to its peak at l d (P<0.01 compared to 2 d, 4 d, 7 d) and then decreased gradually in the boundary zone of the in-farcts.PG 47 μmol/kg and PG 94 μmol/kg could re-duce those damage and neurological deficits significant-ly (P<0.01) ;Furthermore, PG 47 μmol/kg and PG 94 μmol/kg markedly reduced the number of TUNEL positive neurons and increased the immunoreactivity of BDNF at 1d (P<0.01 compared to model) .Dose of 94 μmol/kg PG was more effective .CONCLUSION: The increasing expression of BDNF after cerebral isch-emia-reperfusion injury possibly affect the recovery of the boundary zone of the infarcts;the possible mecha-nism of propyl gallate could protect neurons from isch-emia-reperfusion injury may involve its upregulation of BDNF.

Key words: propyl gallate, cerebral ischemia-reperfusion, BDNF, neuronal apoptosis

中图分类号:

R965.1

林敏, 林智颖, 陈晓春, 郑关毅, 黄俊山, 郑建明, 张静, 周宜灿. 赤芍 801 对大鼠脑缺血/再灌注损伤后脑源性神经营养因子表达的影响[J]. 中国临床药理学与治疗学, 2008, 13(10): 1109-1115.

LIN Min, LIN Zhi-ying, CHEN Xiao-chun, ZHENG Guan-yi, HUANG Jun-shan, ZHENG Jian-ming, ZHANG Jing, ZHOU Yi-can. Effects of propyl gallate on BDNF expression after cerebral ischemia-reperfusion in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(10): 1109-1115.

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