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芍药甘草汤对痉挛性瘫痪大鼠脑内氨基酸含量及受体表达的影响

[Effects of Shaoyao Gancao decoction on contents of amino acids and expressions of receptors in brains of spastic paralysis rats].

作者信息

Wang Jing-Xia, Yang Xu, Zhang Jian-Jun, Zhou Tian-Tian, Zhu Ying-Li, Wang Lin-Yuan

机构信息

Beijing University of Chinese Medicine, Beijing 100029, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2016 Mar;41(6):1100-1106. doi: 10.4268/cjcmm20160621.

Abstract

To explore the effects of Shaoyao Gancao decoction on contents of amino acids and expressions of receptors in the brains of spastic paralysis rats, the spastic paralysis rat models of stroke convalescence were made by line tethering method. Baclofen was used as the control group, and the experiment group received Shaoyao Gancao decoction at 3∶1 proportions. After 3 weeks, the neurobehavioral scores, muscular tension and pain threshold were measured and compared. High performance liquid chromatography (HPLC) was used to detect the contents of GABA, Gly, Glu, Asp in cerebral cortex. The protein expressions of GABA receptors Aα1, B; NMDA receptor NR1, NR2A and NR2B in cerebral cortex were determined by immunohistochemistry assay. The results showed that the Shaoyao Gancao decoction at 3∶1 proportion could improve the spastic paralysis state after stroke, significantly improve neurological symptoms (P<0.01), decrease muscular tension (P<0.01) and improve pain threshold (P<0.05) as compared with model group. Simultaneously, the contents of inhibitory amino acids GABA and Gly were increased significantly (P<0.01), while with a decrease tendency in excitatory amino acids Glu and Asp (with no statistical significance). In addition, it could significantly increase the protein expressions of neurotransmitter GABA receptors Aα1, and B (P<0.05); reduce the expressions of neurotransmitter NMDA receptors NR1, NR2A and NR2B (P<0.05). These results suggested that the Shaoyao Gancao decoction at 3:1 proportion could effectively relieve spasm and pain. The mechanism might be associated with increasing the contents of inhibitory amino acids and increasing the expressions of their receptors in spastic paralysis rats after stroke, which would consequently enhance the signal transduction of inhibitory amino acids. Meanwhile, there was a decrease tendency in excitatory amino acids, although no significant effect was observed, and it could suppress the expressions of excitatory amino acids receptors, thus weaken the excitatory signal transduction. Thereby the neurotoxicity was relieved eventually. These findings indicated that Shaoyao Gancao decoction could regulate the balance of neurotransmitter system to relieve the spasticity, and eventually achieve tendon tonifying and spasm relieving effect.

摘要

为探讨芍药甘草汤对中风恢复期痉挛性瘫痪大鼠脑内氨基酸含量及受体表达的影响,采用线栓法制备中风恢复期痉挛性瘫痪大鼠模型。以巴氯芬为对照组,实验组给予比例为3∶1的芍药甘草汤。3周后,测量并比较神经行为评分、肌张力和痛阈。采用高效液相色谱法(HPLC)检测大脑皮质中γ-氨基丁酸(GABA)、甘氨酸(Gly)、谷氨酸(Glu)、天冬氨酸(Asp)的含量。采用免疫组织化学法检测大脑皮质中GABA受体Aα1、B;N-甲基-D-天冬氨酸(NMDA)受体NR1、NR2A和NR2B的蛋白表达。结果显示,比例为3∶1的芍药甘草汤可改善中风后的痉挛性瘫痪状态,与模型组相比,能显著改善神经症状(P<0.01),降低肌张力(P<0.01),提高痛阈(P<0.05)。同时,抑制性氨基酸GABA和Gly的含量显著增加(P<0.01),而兴奋性氨基酸Glu和Asp呈下降趋势(无统计学意义)。此外,它能显著增加神经递质GABA受体Aα1和B的蛋白表达(P<0.05);降低神经递质NMDA受体NR1、NR2A和NR2B的表达(P<0.05)。这些结果表明,比例为3∶1的芍药甘草汤能有效缓解痉挛和疼痛。其机制可能与增加中风后痉挛性瘫痪大鼠抑制性氨基酸的含量及其受体的表达有关,从而增强抑制性氨基酸的信号转导。同时,兴奋性氨基酸呈下降趋势,虽未观察到显著作用,但可抑制兴奋性氨基酸受体的表达,从而减弱兴奋性信号转导。最终减轻神经毒性。这些研究结果表明,芍药甘草汤可调节神经递质系统平衡以缓解痉挛,最终达到柔筋解痉的效果。

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