Department of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China.
CNS Neurosci Ther. 2011 Dec;17(6):599-604. doi: 10.1111/j.1755-5949.2010.00192.x. Epub 2010 Oct 15.
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.
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.
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).
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.
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。
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。
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)。
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。