摘要
目的观察蛇床子素(Ost)对双侧颈总动脉结扎(BCCAO)致血管性痴呆(VD)大鼠认知功能的影响,并探讨其作用机制。方法将雄性SD大鼠随机分为假手术组、Ost正常对照(40 mg·kg^(-1))组、模型组和Ost20、40 mg·kg^(-1)组(均n = 16)。永久性结扎大鼠双侧颈总动脉致模后第2日给药,每日1次,持续28 d。Morris水迷宫实验观察大鼠的空间学习及记忆能力,HE染色和Nissl染色观察皮质和海马CA1区神经细胞的形态和数量;免疫组化染色观察皮质小胶质细胞改变,Western blot检测炎症因子白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α及炎症趋化因子受体1(CX3CR1)的蛋白表达。结果与假手术组相比,模型组大鼠空间学习及记忆能力显著下降,逃避潜伏期延长、校正潜伏期减少、游泳速度降低(P < 0.05);海马神经元形态受损,且数量减少(P < 0.05);小胶质细胞呈阿米巴样改变,数量增多(P < 0.05);海马中IL-1β、TNF-α和CX3CR1蛋白表达增加(P < 0.05)。与模型组相比,Ost 20、40 mg·kg^(-1)组大鼠空间学习及记忆能力显著改善,逃避潜伏期缩短、校正潜伏期增加及游泳速度加快,海马神经元损伤数量减少(P < 0.05),小胶质细胞数量减少(P < 0.05),海马中IL-1β、TNF-α和CX3CR1蛋白表达降低(P < 0.05)。结论 Ost可改善VD模型大鼠的认知功能损伤,可能与抑制小胶质细胞活化,降低炎症因子IL-1β、TNF-α、CX3CR1的表达有关。
AIM To observe the effect and mechanism of osthole(Ost) on the learning and memory impairments of vascular dementia(VD) rats induced by bilateral common carotid artery occlusion(BCCAO). METHODS Male Sprague Dawley rats were randomly divided into sham group, sham + Ost 40 mg·kg^(-1) group, model group, and Ost 20, 40 mg·kg^(-1) group. Each group was administrated on the second day after permanent ligation of the bilateral common carotid arteries of the rats, twice a day for 28 days. The spatial learning and memory ability of the rats was observed by the Morris water maze. HE staining and Nissl staining were applied to observe the morphology and nerve cells number in the cortex and hippocampus CA1 area. Immunohistochemical staining was used to observe the changes of cortical microglia. The protein expressions of inflammatory mediator interleukin(IL)-1β and tumor necrosis factor-α (TNF-α) and inflammatory chemokine receptor-1(CX3CR1) were assayed by Western blot. RESULTS Compared with the sham group, the spatial learning and memory ability of the model group was significantly decreased, including the escape latency was prolonged, the correction latency was prolonged, the correction latency was decreased, and the swimming speed was decreased(P < 0.05). The hippocampal neurons were damaged and the number was reduced(P < 0.05), and the microglia showed amoebic changes and increased in number(P < 0.05). The protein expressions of IL-1β, TNF-α and CX3CR1 in hippocampus were significantly increased(P < 0.05). Compared with the model group, the Ost 20, 40 mg·kg-1 groups had significantly improved the spatial learning and memory capabilities, the escape latency was reduced and the correction latency was increased and swimming speed was longed(P < 0.05). The number of hippocampal neuronal damage and microglia was decreased(P < 0.05). And the protein expressions of IL-1β, TNF-α and CX3CR1 in hippocampus were significantly decreased(P < 0.05). CONCLUSION Ost can improve the cognitive function damage of VD rats, which may be related to inhibiting the activation of microglia and reducing the expression of inflammatory factors IL-1β, TNF-α and CX3CR1.
作者
丁利静
赵丹丹
刘波
黄艳
李菲
吴芹
熊庭旺
DING Li-jing;ZHAO Dan-dan;LIU Bo;HUANG Yan;LI Fei;WU Qin;XIONG Ting-wang(Department of Pharmacy,Affiliated Hospital of Zunyi Medical University,Zunyi GUIZHOU 563003,China;Key laboratory of Basic Pharmacology of Ministry of Education&Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi GUIZHOU 563099,China;Research Department,Zunyi Medical and Pharmaceutical College,Zunyi GUIZHOU 563006,China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2021年第6期470-475,共6页
Chinese Journal of New Drugs and Clinical Remedies
基金
贵州省科技厅联合资金项目(黔科合LH字[2014]7571号)。