丁苯酞对血管性痴呆大鼠海马CA1区脑源性神经营养因子表达的影响

doi:10.13481/j.1671-587x.20170501

摘要/Abstract

摘要： 目的：观察丁苯酞（NBP）对血管性痴呆（VD）大鼠海马CA1区脑源性神经营养因子（BDNF）表达的影响，探讨丁苯酞对VD的保护作用。方法：将80只健康Wistar大鼠按随机区组法分为假手术组、NBP对照组（假手术+NBP注射剂）、VD组（VD模型）和NBP处理组（VD模型+NBP注射剂），每组20只，每组又分为4个亚组，即术后1、2、4和8周组，每个亚组5只。永久性双侧颈总动脉结扎法制备VD大鼠模型。NBP对照组和NBP处理组大鼠腹腔注射NBP注射剂5 mg·kg^-1·d^-1，连续给药7 d。假手术组和VD组大鼠每次腹腔注射4 mL生理盐水，连续注射7 d。各组大鼠在术后各时间点（1、2、4和8周）留取海马组织，应用实时定量PCR和免疫组织化学法检测各组大鼠海马CA1区BDNF表达水平。结果：定时定量PCR法，术后2、4和8周，VD组大鼠海马BDNF mRNA表达水平明显高于假手术组（P < 0.05），术后4和8周，NBP处理组大鼠海马BDNFmRNA表达水平明显高于VD组（P < 0.05）；免疫组织化学法，VD组大鼠4周时BDNF表达水平明显高于假手术组（P < 0.05），术后8周时NBP组大鼠CA1区BDNF蛋白表达水平明显高于VD组（P < 0.05）。结论：VD模型大鼠海马CA1区神经元在遭受缺血损伤后，BDNF反应性表达增加，而NBP则可明显提高VD大鼠海马CA1区BDNF的表达，发挥神经保护作用。

关键词: 血管性痴呆, 脑源性神经营养因子, 丁苯酞, 海马

Abstract: Objective: To study the effect of 3-n-butylphthalide (NBP) on the expression of brain-derived neurotrophic factor (BDNF) in the hippocampal CA1 region of the vascular dementia (VD) rats, and to explore its protective effect on VD. Methods: Eighty healthy Wistar rats were equally and randomly assigned to sham operation group, NBP control group (sham operation + NBP injection), VD group (VD models), NBP treatment group (VD models + NBP injection)(n=20). Each group was divided into four subgroups (n=5):1, 2, 4, and 8 weeks after operation groups. The VD rat models were established by using permanent bilateral common carotid artery ligation. After consciousness, the rats in NBP treatment group and NBP control group were intraperitoneally injected with 5 mg·kg^-1·d^-1 NBP for consecutive 7 d. The rats in VD and sham operation groups were intraperitoneally injected with 0.2 mL·d^-1 saline for consecutive 7 d. At 1, 2, 4, and 8 weeks after operation, the rats in each group were decapitated. The brains were obtained, and then the hippocampus tissues were isolated. The BDNF expression levels in the hippocampal CA1 region were determined using real-time quantitative PCR and immunohistochemistry methods. Results: At 2, 4, and 8 weeks after s operation, the expression levels of BDNF mRNA in the hippocampus of the rats in VD group were significantly higher those in sham operation group(P<0.05);at 4 and 8 weeks after operation, the expression levels of BDNF mRNA in the hippocampus of the rats in NBP treatment groups were significantly higher than that in VD group(P<0.05).The immunohistochemistry results showed that the expression level of BDNF protein in the hippocampal CA1 region of the rats in VD group was higher than that in sham operation group at 4 weeks after operation (P<0.05); the expression level of BDNF protein in the hippocampal CA1 region of the rats in NBP treatment group was higher than that in VD group at 8 weeks after operation (P<0.05). Conclusion: The BDNF expression is increased in the hippocampal CA1 region of the rats with VD after the neurons were injured by ischemia. NBP can increase the BDNF expression level in the hippocampal CA1 region of the VD rats and protect the nerves.

Key words: vascular dementia, hippocampus, 3-n-butylphthalide, brain-derived neurotrophic factor

中图分类号:

R743

毛西京, 王敏, 于挺敏, 姚刚. 丁苯酞对血管性痴呆大鼠海马CA1区脑源性神经营养因子表达的影响[J]. 吉林大学学报(医学版), 2017, 43(05): 857-861.

MAO Xijing, WANG Min, YU Tingmin, YAO Gang. Effect of 3-n-butylphthalide on brain-derived neurotrophic factor expression in hippocampal CA1 region of vascular dementia rats[J]. Journal of Jilin University Medicine Edition, 2017, 43(05): 857-861.

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