Militarine改善慢性脑缺血大鼠认知功能障碍及白质损伤的研究

Militarine alleviates white matter damage and cognitive impairment in rats with chronic cerebral hypoperfusion

研究1,4-二[4-(葡萄糖氧)苄基]-2-异丁基苹果酸酯(militarine)对慢性脑缺血大鼠认知功能障碍及脑白质损伤的影响。采用永久性双侧颈总动脉结扎建立慢性脑缺血大鼠模型。通过Morris水迷宫法检测大鼠学习记忆能力;牢固蓝(luxol fast blue,LFB)染色法检测大鼠胼胝体白质髓鞘的变化;Western blot检测大鼠胼胝体髓鞘碱性蛋白(myelin basic protein,MBP)的表达;免疫组织荧光技术检测大鼠胼胝体环核苷酸磷酸二酯酶(2',3'-cyclic-nucleotide 3'-phosphodiesterase,CNPase)阳性细胞的改变。结果显示,militarine可改善慢性脑缺血大鼠在水迷宫实验中的表现,在20 mg·kg^(-1)·d^(-1)剂量下大鼠逃避潜伏期、首次穿越原平台位置时间明显缩短,穿越原平台的次数明显增加。同时,胼胝体白质脱髓鞘现象得到明显改善,MBP表达明显上调,CNPase阳性细胞数量明显增加。提示militarine能够改善慢性脑缺血大鼠的认知功能障碍,减轻脑白质缺血性损伤。

Chronic cerebral hypoperfusion is a model for white matter lesions（WMLs） and cognitive impairment.In this study,we used the model in testing the protective effect of（-）-（2R）-1-[（4-β-D-glucopyranosyloxy）benzyl]-4-[4-（β-D-glucopyranosyloxy）benzyl]-2-isobutyl malate（militarine） on the white matter damaged.The model was established by bilateral common carotid ligation.Militarine（10 and 20 mg·kg^-1·d^-1） or saline was intragastrically administered daily for 30 days following the operation.Militarine（20 mg·kg^-1d^-1）-treated rats exhibited significantly shorter escape latency,latency of the first time crossing and more numbers of platform crossings in Morris water maze task.Luxol fast blue（LFB） staining and Western blot analysis indicated that militarine promoted rehabilitation of white matter and increased levels of myelin basic protein（MBP） in the rats.Immunohistochemical staining for 2＇,3＇-cyclic-nucleotide 3＇-phosphodiesterase（CNPase） revealed that militarine（20 mg·kg^-1·d-^-1） markedly suppressed loss of CNPase-positive oligodendrocytes in the rat model.In conclusion,militarine can improve WMLs and cognitive impairment in the rat chronic hypoperfusion model.