Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats.
Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats.
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欧前胡素对血管性痴呆大鼠细胞凋亡和突触可塑性的影响
DOI：
10.1038/s41598-021-88206-7
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发表时间：
2021-04-21
影响因子：
4.6
通讯作者：
Xie F
中科院分区：
文献类型：
--
作者：
Huang Y;Liao X;Wang H;Luo J;Zhong S;Zhang Z;Zhang F;Chen J;Xie F
鉴于血管性痴呆（vascular dementia，VD）复杂的病理生理过程，目前临床治疗VD的药物主要针对相关危险因素，而对认知功能疗效优异的药物仍相对缺乏。欧前胡素（Imperatorin，IMP）是从白芷（Angelica dahuricae）和羌活（Notopterygium Notopterygii）中提取的有效成分，具有抗炎、舒张血管、抗凝血、阻断钙通道、抗惊厥、抗氧自由基损伤等作用。因此，本研究探讨其对VD大鼠的作用及其分子机制，以期为VD的治疗提供新的思路和方法。采用改良的永久性二血管闭塞（2 VO）结扎法建立VD模型。2 VO手术后，连续12周腹腔注射IMP（2.5、5和10 mg/kg）以评价治疗效果。Morris水迷宫检测认知功能。苏木精-伊红染色观察神经元形态学变化。Real-Time PCR和Western blot检测促凋亡和抗凋亡生物标志物，透射电镜观察海马突触损伤。结果表明，2 VO可引起大鼠认知功能障碍、海马CA 1区神经元损伤、细胞凋亡和突触损伤。IMP治疗显著改善2 VO诱导的认知缺陷和海马神经元损伤。分子生物学分析表明，IMP通过下调Bax、Caspase-3和上调Bcl-2的表达来抑制细胞凋亡。同时，IMP处理显著改善突触超微结构形态，增加SAZ长度和PSD厚度，并上调PSD-95表达。以上结果表明，IMP对2 VO诱导的VD有明显的治疗作用，其机制可能与抑制海马神经元凋亡、减轻突触可塑性破坏有关。
In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extracted from angelica dahuricae and notopterygium Notopterygii, which has anti-inflammatory, vasodilator, anticoagulant, block calcium channel, anticonvulsant, and anti oxygen free radical injury properties. Therefore,the present study examined its effects on VD rats and the underlying molecular mechanisms, in order to provide promising therapeutic methods. VD was established by modified ligation of perpetual two-vessel occlusion (2VO). After 2VO surgery, IMP (2.5, 5, and 10 mg/kg) was administered by intraperitoneal injection for 12 consecutive weeks to evaluate therapeutic effects. Cognitive function was verified by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin–Eosin staining. Real-Time PCR and Western blot were used for detecting pro- and antiapoptotic biomarkers, and the hippocampus synaptic damage was examined by Transmission electron microscope. We revealed that 2VO-induced cognitive impairment, hippocampus CA1 neuron damage, apoptosis and synaptic damage. IMP-treatment significantly improved 2VO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that IMP inhibited apoptosis through the down regulation of Bax, Caspase-3 and upregulation of Bcl-2. Meanwhile, IMP-treatment markedly improved synaptic ultrastructure morphology, increased the SAZ length, PSD thickness and up-regulated PSD-95 expression. Collectively, our findings demonstrated that IMP was effective in the treatment of 2VO-induced VD via inhibiting apoptosis of hippocampus neurons and reducing the synaptic plasticity destroy.
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影响因子：
5.6
作者：
Liu B;Gao JM;Li F;Gong QH;Shi JS
通讯作者：
Shi JS
影响因子：
2.2
作者：
Singh, Gurjit;Kaur, Jashanpreet;Bhatti, Rajbir
通讯作者：
Bhatti, Rajbir
血管性痴呆大鼠模型中与信息流改变相关的突触可塑性下降
影响因子：
3.3
作者：
Xu, X.;Li, Z.;Zhang, T.
通讯作者：
Zhang, T.
影响因子：
2.6
作者：
Kim, Sook Hui;Kang, Hyun Seok;Han, Seol-Heui
通讯作者：
Han, Seol-Heui
运动可改善血管性痴呆模型大鼠前额皮质的识别记忆和突触可塑性
影响因子：
1.9
作者：
Dong, Juntao;Zhao, Jingpu;Yan, Tiebin
通讯作者：
Yan, Tiebin