丁苯酞对血管性痴呆大鼠记忆能力及海马CA1区Caspase-3表达的影响  

Effects of 3-n-butylphthalide on memory and Caspase-3 expression in the hippocampal CA1 region of vascular dementia rats

作　　者：毛西京[1] 朱博驰[1] 于挺敏[1] 姚刚[1] MAO Xijing ZHU Bochi YU Tingmin YAO Gang(Department of Neurology, the Second Hospital of Jilin University, Jilin Province, Changchun 130041, China)

机构地区：[1]吉林大学第二医院神经内科,吉林长春130041

出　　处：《中国医药导报》2017年第28期9-12,F0004,共5页China Medical Herald

基　　金：国家自然科学基金资助项目(81500953);吉林省科技厅科技发展计划资助项目(20150520143JH)

摘　　要：目的观察丁苯酞对血管性痴呆大鼠记忆能力及海马CA1区凋亡基因Caspase-3表达的影响,探讨丁苯酞对血管性痴呆的保护作用。方法将80只SPF级健康Wistar大鼠按随机区组法分为4个组,每组20只:血管性痴呆模型组(VD组)、血管性痴呆模型+丁苯酞氯化钠注射液组(NBP治疗组)、假手术+丁苯酞氯化钠注射液组(NBP对照组)、假手术组(Sham组),每组再分为4个亚组:术后1、2、4、8周,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治疗组大鼠术后1 d开始给予丁苯酞氯化钠注射液腹腔注射,剂量为5 mg/(kg·d),Sham组和VD组大鼠给予生理盐水腹腔注射(0.2 mL/d)。各组大鼠连续腹腔注射给药7 d。术后8周亚组大鼠,在术前、术后4周和术后8周进行记忆能力测试(Morris水迷宫)。术后各时间点(1、2、4、8周),留取海马组织,采用免疫组化法观察各组大鼠海马CA1区Caspase-3的表达。结果 NBP治疗组大鼠逃避潜伏期较VD组大鼠明显缩短(P<0.05)。VD组和NBP治疗组大鼠海马CA1区Caspase-3蛋白表达灰度明显高于Sham组(P<0.05);术后4周和8周时,NBP治疗组大鼠海马CA1区Caspase-3蛋白表达均明显低于VD组大鼠相应时间点(P<0.05)。VD大鼠术后8周时海马CA1区Caspase-3表达灰度明显高于术后1周时(P<0.05)。结论NBP对VD大鼠记忆能力有明显改善作用,考虑与其抑制VD大鼠海马CA1区Caspase-3过度表达有关。Objective To study the effects of 3-n-butylphthalide （NBP） on memory and Caspase-3 expression in the hippocampal CA1 region of vascular dementia rats, in order to explore protective effects and mechanisms of NBP on rats with vascular dementia （VD）. Methods A total of 80 SPF Wistar rats were divided into vascular dementia models group （VD group）, vascular dementia models ＋ NBP injection group （NBP treatment group）, sham surgery ＋ NBP injection group （NBP control group）, sham surgery group （Sham group）, according to random group method. Then each group was divided into four subgroups （n = 5）： 1, 2, 4, and 8 weeks after surgery. VD models were established by ligating bilateral common carotid artery. Then the rats in the NBP treatment group and NBP control group were intraperitoneally injected with NBP 5 mg/（kg·d） for 7 consecutive days. The rats in the VD group and Sham group were intraperitoneally injected with saline （0.2 mL/d） for 7 consecutive days. Memory ability of 8 weeks subgroup rats were tested by Morris water maze at 4 and 8 weeks after surgery. At 1, 2, 4, and 8 weeks after surgery, the rats in each group were decapitated. The brains were obtained, and then hippocampus were isolated. Caspase-3 expression in the hippoeampal CA1 region were deter- mined by immunohistochemistry. Results Compared with VD group, escape latency in the NBP treatment group were significantly shorter （P 〈 0.05）. At 1, 2, 4 and 8 weeks after surgery, Caspase-3 expression in the VD group and NBP treatment group were significantly increased than those in the Sham group （P 〈 0.05）. Compared with VD group, Caspase-3 expression in the NBP treatment group were significantly lower at 4 and 8 weeks after surgery （P 〈 0.05）. In VD group, Caspase-3 expression at 8 weeks after surgery was significantly higher than at 1 weeks （P 〈 0.05）. Conclusion NBP can improve the memory ability of VD rats, which may be connected with the overexpression of caspase-3 in the hippocampus CA1

关 键 词：丁苯酞 血管性痴呆 海马 细胞凋亡 

分 类 号：R743[医药卫生—神经病学与精神病学]