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
作者
毛西京
朱博驰
于挺敏
姚刚
MAO Xijing ZHU Bochi YU Tingmin YAO Gang(Department of Neurology, the Second Hospital of Jilin University, Jilin Province, Changchun 130041, China)
出处
《中国医药导报》
CAS
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)
关键词
丁苯酞
血管性痴呆
海马
细胞凋亡
3-n-butylphthalide
Vascular dementia
Hippocampus
Cell apoptosis
