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本文引用的文献

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[Effects of electro-acupuncture on electroencephalography in patients with vascular dementia].[电针对血管性痴呆患者脑电图的影响]
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2006 Aug;26(8):738-40.
2
Mitochondrial translocation of p53 mediates release of cytochrome c and hippocampal CA1 neuronal death after transient global cerebral ischemia in rats.p53的线粒体转位介导大鼠短暂性全脑缺血后细胞色素c的释放及海马CA1区神经元死亡。
J Neurosci. 2006 Jul 26;26(30):7974-83. doi: 10.1523/JNEUROSCI.0897-06.2006.
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Apoptosis dominant in the periinfarct area of human ischaemic stroke--a possible target of antiapoptotic treatments.凋亡在人类缺血性脑卒中梗死周边区域占主导地位——抗凋亡治疗的一个可能靶点。
Brain. 2006 Jan;129(Pt 1):189-99. doi: 10.1093/brain/awh645. Epub 2005 Nov 4.
4
Involvement of Noxa in cellular apoptotic responses to interferon, double-stranded RNA, and virus infection.Noxa参与细胞对干扰素、双链RNA和病毒感染的凋亡反应。
J Biol Chem. 2005 Apr 22;280(16):15561-8. doi: 10.1074/jbc.M412630200. Epub 2005 Feb 10.
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Emerging therapies for vascular dementia and vascular cognitive impairment.血管性痴呆和血管性认知障碍的新兴疗法。
Stroke. 2004 Apr;35(4):1010-7. doi: 10.1161/01.STR.0000120731.88236.33. Epub 2004 Mar 4.
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BH3-only protein Noxa is a mediator of hypoxic cell death induced by hypoxia-inducible factor 1alpha.仅含BH3结构域的蛋白Noxa是缺氧诱导因子1α诱导的缺氧细胞死亡的介质。
J Exp Med. 2004 Jan 5;199(1):113-24. doi: 10.1084/jem.20030613. Epub 2003 Dec 29.
7
Up-regulation of Bcl-2 homology 3 (BH3)-only proteins by E2F1 mediates apoptosis.E2F1介导的Bcl-2同源结构域3(BH3)-仅含蛋白的上调介导细胞凋亡。
J Biol Chem. 2004 Mar 5;279(10):8627-34. doi: 10.1074/jbc.M312866200. Epub 2003 Dec 18.
8
Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription.在不存在转录的情况下,p53的药理学激活引发依赖Bax的细胞凋亡。
Cancer Cell. 2003 Nov;4(5):371-81. doi: 10.1016/s1535-6108(03)00272-1.
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Apoptosis and caspases in neurodegenerative diseases.神经退行性疾病中的细胞凋亡与半胱天冬酶
N Engl J Med. 2003 Apr 3;348(14):1365-75. doi: 10.1056/NEJMra022366.
10
Ischemic intensity influences the distribution of delayed infarction and apoptotic cell death following transient focal cerebral ischemia in rats.缺血强度影响大鼠短暂性局灶性脑缺血后延迟性梗死和凋亡性细胞死亡的分布。
Brain Res. 2002 Nov 22;956(1):14-23. doi: 10.1016/s0006-8993(02)03197-9.

电针对血管性痴呆大鼠海马 CA1 区锥体神经元的保护作用与抑制 p53、Noxa 的表达有关。

Electroacupuncture protected pyramidal cells in hippocampal CA1 region of vascular dementia rats by inhibiting the expression of p53 and Noxa.

机构信息

Department of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China.

出版信息

CNS Neurosci Ther. 2011 Dec;17(6):599-604. doi: 10.1111/j.1755-5949.2010.00192.x. Epub 2010 Oct 15.

DOI:10.1111/j.1755-5949.2010.00192.x
PMID:20950325
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6493847/
Abstract

AIM

Clinically electroacupuncture (EA) is proved an effective therapy for vascular dementia (VD), but their mechanisms remain uncertain. The aim of this study was to determine whether EA protects pyramidal cells from apoptosis in hippocampus of a VD rat model by inhibiting the expression of p53 and Noxa.

METHODS

One month after a VD animal model was established by bilateral occlusion of common carotid arteries, EA treatment was given at "Baihui" (DU20), "Dazhui" (DU14), and "Shenshu" (BL23). The learning and memory ability was assessed by Morris water maze. Neuronal apoptosis in hippocampus was evaluated with hematoxylin-eosin (HE) staining, and the expression of p53 and Noxa was analyzed by confocal laser scanning microscope with immunofluorescence staining.

RESULTS

Expressions of p53 and Noxa in the EA group and sham-operated group were less than in the VD model group (P < 0.01), and the expression of p53 was positively correlated to expression of Noxa in hippocampus of VD rats (r = 0.918, P < 0.01). EA treatment could reduce the amount of apoptotic neurons in hippocampal CA1 area of rats with VD. The average latency in the Morris water maze test was significantly shorter, and escape strategies improved from edge and random searches to more linear swim pathway in the EA group compared with the VD model group (P < 0.01).

CONCLUSIONS

The increasing expressions of p53 and Noxa play important roles in the pathogenesis of VD. EA improves learning and memory ability and protects pyramidal cells from apoptosis by blocking expression of p53 and Noxa in the hippocampal CA1 region of VD rats. These results suggest a novel mechanism of EA treatment to VD.

摘要

目的

临床电针(EA)已被证明是血管性痴呆(VD)的有效治疗方法,但它们的机制仍不清楚。本研究旨在通过抑制 p53 和 Noxa 的表达,确定 EA 是否通过保护海马锥体神经元免于凋亡来治疗 VD 大鼠模型。

方法

在通过双侧颈总动脉闭塞建立 VD 动物模型 1 个月后,给予 EA 治疗,穴位为“百会”(DU20)、“大椎”(DU14)和“肾俞”(BL23)。采用 Morris 水迷宫评估学习和记忆能力。苏木精-伊红(HE)染色评估海马神经元凋亡,免疫荧光染色结合共聚焦激光扫描显微镜分析 p53 和 Noxa 的表达。

结果

EA 组和假手术组的 p53 和 Noxa 表达均低于 VD 模型组(P<0.01),并且 VD 大鼠海马 p53 的表达与 Noxa 的表达呈正相关(r=0.918,P<0.01)。EA 治疗可减少 VD 大鼠海马 CA1 区凋亡神经元的数量。与 VD 模型组相比,EA 组大鼠在 Morris 水迷宫测试中的平均潜伏期明显缩短,逃避策略从边缘和随机搜索改善为更线性的游泳路径(P<0.01)。

结论

p53 和 Noxa 的表达增加在 VD 的发病机制中起重要作用。EA 通过阻断 VD 大鼠海马 CA1 区 p53 和 Noxa 的表达,改善学习和记忆能力,并保护锥体神经元免于凋亡。这些结果提示了 EA 治疗 VD 的一种新机制。