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瓜蒌桂枝汤通过调节兴奋性氨基酸及其受体表达对局灶性脑缺血再灌注损伤的影响

Effect of Gua Lou Gui Zhi decoction on focal cerebral ischemia-reperfusion injury through regulating the expression of excitatory amino acids and their receptors.

作者信息

Chen Xianwen, Li Huang, Huang Mingqing, Huang Mei, Xu Wei, Chu Kedan, Chen Lidian, Zhang Yuqin

机构信息

College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.

College of Rehabilitation Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.

出版信息

Mol Med Rep. 2014 Jul;10(1):248-54. doi: 10.3892/mmr.2014.2189. Epub 2014 Apr 28.

DOI:10.3892/mmr.2014.2189
PMID:24788947
Abstract

Gua Lou Gui Zhi decotion (GLGZD) has been reported to be an effective treatment for post‑apoplectic limb spasm in the clinic. The present study aimed to investigate whether GLGZD had an affect on cerebral injuries induced by middle cerebral artery occlusion (MCAO) in rats and its possible mechanism. High‑performance liquid chromatography was performed to analyze GLGZD. Furthermore, a model was established to assess the efficacy of GLGZD. Neurological defect scores and screen tests were analyzed. Brain ischemic infarct volume was measured using 2,3,5‑triphenyl tetrazolium chloride staining and glutamic acid (Glu), aspartic acid (Asp) and glycine (Gly) levels in the cerebrospinal fluid were measured using the Hitachi automatic amino acid analyzer. Immunohistochemistry was performed to determine the expression of the α‑amino‑3‑hydroxy‑5‑methyl‑4‑isoxazole‑propionic acid (AMPA) and N‑methyl‑D‑aspartic acid (NMDA) glutamate receptors, and to analyze histopathological change. GLGZD was found to improve neurological performance and reduce infarct volumes in MCAO rats. In addition, GLGZD was observed to enhance motor performance, which was assessed using the screen test. Furthermore, GLGZD was found to reduce Glu, Asp and Gly levels in the cerebrospinal fluid and downregulate the protein expression of the AMPA and NMDA glutamate receptors. Thus, it was demonstrated that GLGZD may exert neuroprotective effects through the modulation of excitatory amino acids, and AMPA and NMDA receptor expression.

摘要

瓜蒌桂枝汤在临床上已被报道是治疗中风后肢体痉挛的有效方剂。本研究旨在探讨瓜蒌桂枝汤对大鼠大脑中动脉闭塞(MCAO)所致脑损伤的影响及其可能机制。采用高效液相色谱法分析瓜蒌桂枝汤。此外,建立模型评估瓜蒌桂枝汤的疗效。分析神经功能缺损评分和筛选试验。采用2,3,5-三苯基四氮唑氯化物染色法测量脑缺血梗死体积,并用日立自动氨基酸分析仪测量脑脊液中谷氨酸(Glu)、天冬氨酸(Asp)和甘氨酸(Gly)水平。采用免疫组织化学法检测α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)和N-甲基-D-天冬氨酸(NMDA)谷氨酸受体的表达,并分析组织病理学变化。结果发现瓜蒌桂枝汤可改善MCAO大鼠的神经功能,减少梗死体积。此外,通过筛选试验评估发现瓜蒌桂枝汤可增强运动能力。此外,还发现瓜蒌桂枝汤可降低脑脊液中Glu、Asp和Gly水平,并下调AMPA和NMDA谷氨酸受体的蛋白表达。因此,证明瓜蒌桂枝汤可能通过调节兴奋性氨基酸以及AMPA和NMDA受体表达发挥神经保护作用。

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