化痰开窍方对慢性脑低灌注损伤小鼠认知行为及突触可塑性的影响

Effectiveness of the Huatan Kaiqiao prescription on cognitive behavior and synaptic plasticity in mice with chronic cerebral hypoperfusion injury

中文关键词: 血管性认知障碍    慢性脑低灌注损伤    突触可塑性    化痰开窍方    双侧颈动脉狭窄

英文关键词: vascular cognitive impairment  chronic cerebral hypoperfusion injury  synaptic plasticity  Huatan Kaiqiao prescription  bilateral carotid artery stenosis

中文摘要:

      目的 探讨化痰开窍方对慢性脑低灌注损伤小鼠认知行为学及突触可塑性的影响。方法 将24只SPF级C57BL/6J雄性小鼠随机分为假手术组(Sham组)、模型组(BCAS组)和中药干预组(HTKQ组),每组8只。采用双侧颈动脉狭窄法(BCAS)构建小鼠慢性脑低灌注损伤模型。造模成功后HTKQ组给予化痰开窍方灌胃，连续14 d。采用激光散斑血流成像系统记录全脑血流(CBF);通过旷场实验、新物体识别和Y迷宫等行为学测试评估化痰开窍方对小鼠神经行为功能的影响；蛋白质印迹法检测小鼠脑组织突触后密度蛋白95(PSD-95)和突触囊泡蛋白(SYP)的表达。结果 激光散斑结果显示，BCAS术后小鼠CBF下降至术前的69%～80%(P<0.01)。行为学实验显示，术后4周BCAS组认知功能受损(P<0.05),化痰开窍方干预可有效改善其认知损伤(P<0.05)。蛋白质印迹结果显示，化痰开窍方能改善慢性脑低灌注损伤引起的PSD-95蛋白表达下调(P<0.05),但对SYP表达无显著影响。结论 化痰开窍方能有效改善慢性脑低灌注损伤小鼠的认知功能障碍，其作用机制可能与上调PSD-95表达，修复突触后可塑性有关。

英文摘要:

      Objective To investigate the effects of the Huatan Kaiqiao Formula(HTKQ)on cognitive behavior and synaptic plasticity in mice with chronic cerebral hypoperfusion injury(CCH).Methods Twenty-four male SPF C57 BL/6 J mice were randomly divided into three groups(n=8 per group):a sham-operated group(Sham),a model group induced by bilateral common carotid artery stenosis(BCAS),and a Chinese medicine intervention group(HTKQ).After successful modeling,mice in the HTKQ group were administered the Huatan Kaiqiao Formula via gavage for 14 consecutive days.Cerebral blood flow(CBF)was monitored using laser speckle contrast imaging.Behavioral tests,including the open field test,novel object recognition test,and Y-maze test,were performed to assess neurobehavioral function.The protein expression levels of postsynaptic density protein 95(PSD-95)and synaptophysin(SYP)in brain tissue were detected by western blot analysis.Results Laser speckle imaging revealed that CBF decreased to 69%-80%of the baseline level post-BCAS(P<0.01).Behavioral tests at 4 weeks post-surgery indicated significant cognitive impairment in the BCAS group(P<0.05),which was effectively ameliorated by HTKQ treatment(P<0.05).Western blot results showed that HTKQ intervention mitigated the CCH-induced downregulation of PSD-95 protein expression(P<0.05),but had no significant effect on SYP expression.Conclusion The Huatan Kaiqiao Formula effectively improves cognitive dysfunction in mice with CCH.Its mechanism may be associated with upregulating PSD-95 expression and restoring postsynaptic plasticity.