丁苯酞对血管性痴呆大鼠胼胝体髓鞘的保护作用  

The protective effect of Dl-3-n-butylphthalide on myelin sheath of corpus callosum in rats with vascular dementia

作　　者：李美锡[1] 高雅然[1] 牛小莉[1] 成斯琪 王天俊[1] 赵景茹[1] 吕佩源[1] LI Mei-xi;GAO Ya-ran;NIU Xiao-li;CHENG Si-qi;WANG Tian-jun;ZHAO Jing-ru;LV Pei-yuan(Department of Neurology,Hebei General Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北省人民医院神经内科,石家庄050051

出　　处：《中国新药杂志》2022年第10期1013-1018,共6页Chinese Journal of New Drugs

基　　金：河北省高端人才资助项目(6833452;83587216);河北省政府资助临床医学优秀人才培养项目(冀财社:2019-139-5);河北省科技创新团队资助项目(冀政2020-9号5-2);河北省引智项目(冀科专函:2020-19-2);河北省医学科学研究重点课题资助项目(青年科技课题20190010)。

摘　　要：目的:探索丁苯酞对血管性痴呆大鼠胼胝体髓鞘的保护作用及其机制。方法:将血管性痴呆大鼠分为模型组(Model组)与丁苯酞干预组,行水迷宫测试,取材后采用劳克坚牢蓝(luxol fast blue,LFB)染色、Western blot及实时荧光定量PCR(RT-qPCR)法检测髓鞘相关蛋白及AMPK/SIRT1信号通路表达情况。结果:丁苯酞组逃避潜伏期缩短,目标象限停留时间百分比增加。模型组较假手术组(Sham组)髓鞘脱失进行性加重(LFB染色、MBP mRNA、MBP蛋白:所有P <0.001),丁苯酞干预后髓鞘脱失程度减轻(P <0.001),伴随着AMPK/SIRT1通路的上调(P <0.05)。结论:丁苯酞对血管性痴呆大鼠的认知功能以及胼胝体髓鞘具有保护作用,这种保护作用可能在一定程度上与AMPK/SIRT1通路的激活有关。Objective: To explore the protective effect of Dl-3-n-butylphthalide on myelin sheath of corpus callosum in rats with vascular dementia( VD) and the potential mechanism. Methods: VD rats were given vehicle or Dl-3-n-butylphthalide of gradient concentration for 2 or 4 weeks after operation. Water maze test was performed to test the spatial learning and memory ability. LFB staining was made to evaluate the demyelination. Western blot and RT-qPCR were performed to examine the expression of myelin-related proteins and the AMPK/SIRT1 signaling pathway. Results: The escape latency of Dl-3-n-butylphthalide-treated rats was shorter but the time spent in the target quadrant was longer( P < 0. 05). Compared with the sham operation group,demyelination in the model group was progressively aggravated( LFB staining,MBP mRNA level and MBP protein level,all P < 0. 001). However,the demyelination in the VD rats was alleviated after Dl-3-n-butylphthalide treatment( P < 0. 001),accompanied by the up-regulation of AMPK/SIRT1 pathway( P < 0. 05). Conclusion: Dl-3-n-butylphthalide plays a protective role on myelin sheath of corpus callosum and cognitive function in rats with vascular dementia,which probably is related to the AMPK/SIRT1 signaling pathway.

关 键 词：血管性痴呆 髓鞘脱失 髓鞘保护 丁苯酞 

分 类 号：R965[医药卫生—药理学]