DL-3-n-butylphthalide alleviates vascular cognitive impairment by regulating endoplasmic reticulum stress and the Shh/Ptch1 signaling-pathway in rats
DL-3-n-butylphthalide alleviates vascular cognitive impairment by regulating endoplasmic reticulum stress and the Shh/Ptch1 signaling-pathway in rats
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DOI：
10.1002/jcp.27332
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Lv, Pei-Yuan
中科院分区：
文献类型：
--
作者：
Niu, Xiao-Li;Jiang, Xin;Lv, Pei-Yuan
ddl -3-正丁基酞（NBP）已被证实可有效改善认知缺陷。本研究的目的是确定NBP是否通过调节sonic hedgehog (Shh)/ patche1 （Ptch1）通路和内质网应激（ERS）相关标记物来保护慢性脑灌注不足（CCH）诱导的血管性痴呆（VD）大鼠模型中的认知缺陷。方法采用双侧颈总动脉永久性闭塞（2VO）法制备成年雄性Sprague-Dawley大鼠颈总动脉永久性闭塞模型。将大鼠随机分为5组：假手术组、模型组、NBP30 （30mg/kg）组、NBP (60) （60mg/kg）组、NBP (120) （120mg/kg）组。术后4周采用Morris水迷宫试验评估认知功能。结果snbp可显著减轻大鼠空间学习记忆障碍，抑制海马CA1区神经元的丢失。Western blot分析和实时定量聚合酶链反应分析显示，NBP处理组可塑性相关突触标志物和Shh/Ptch1通路显著升高，ers相关标志物降低。结论本研究结果证明Shh/Ptch1通路在VD模型中起重要作用。NBP对CCH所致的认知损伤有保护作用。这一机制与ERS和Shh/Ptch1通路有关。同时，Shh/Ptch1通路和ERS可能相互作用。
BackgroundDL-3-n-butylphthalide (NBP) has been approved to be effective in improving cognitive deficits. The aim of the current study was to determine whether NBP protects against cognitive deficits in a rat model of vascular dementia (VD) induced by chronic cerebral hypoperfusion (CCH) by regulating the sonic hedgehog (Shh)/patched1 (Ptch1) pathway and endoplasmic reticulum stress (ERS)-related markers.MethodsAdult male Sprague-Dawley rats were subjected to permanent bilateral occlusion of the common carotid arteries (2VO) to established the model of VD. These rats were randomly divided into five groups: sham, model, NBP30 (30mg/kg), NBP (60) (60mg/kg), and NBP (120) (120mg/kg) groups. The Morris water maze test was used to assess for cognitive function at 4 weeks after operation.ResultsNBP significantly alleviated spatial learning and memory impairment, and inhibited the loss of neurons in the CA1 region of the hippocampus. Western blot analysis and real-time quantitative polymerase chain reaction analysis revealed that plasticity-related synaptic markers and the Shh/Ptch1 pathway significantly increased in the NBP treated groups, while ERS-related markers decreased.ConclusionThe results of the current study prove that the Shh/Ptch1 pathway plays an essential role in the model of VD. NBP had protective effects on cognitive impairment induced by CCH. This mechanism was associated with ERS and the Shh/Ptch1 pathway. Meanwhile, the Shh/Ptch1 pathway and ERS may interact with each other.