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基于胃寒证模型的吴茱萸挥发油疗效及伴随毒副作用研究

[Study on efficacy and accompanying toxic and side effects of volatile oil of Evodia Fructus based on stomach cold syndrome model].

作者信息

Li Xiao-yu, Sun Rong

出版信息

Zhongguo Zhong Yao Za Zhi. 2015 Oct;40(19):3838-44.

Abstract

OBJECTIVE

To preliminarily study the effective dosage range and mechanism of the abirritation of volatile oil of Evodia Fructus on the stomach cold syndrome model in mice, and discuss the correlation between its accompanying toxicity and oxidative damage mechanism, in order to provide the experimental basis for explaining the efficacy-syndrome-toxicity correlation.

METHOD

The stomach cold-syndrome model in mice was induced by the classic hot plate test by orally administrating with different doses of volatile oil of Evodia Fructus, in order to observe its abirritation and companying toxic and side effects and detect serum ALT, AST, PGE2, NO, NOS, MDA, SOD, GSH, GSH-Px, BUN, CR and hepatic ALT, AST. The companying toxic symptoms in mice were recorded in toxic reaction integral table.

RESULT

Volatile oil of Evodia Fructus had an obvious analgesic effect at 30 min after the oral administration and reached the peak effect at 60 min, with certain "dose-effect" and "time-effect" relations, rises in serum and hepatic ALT and AST levels, serum PGE2, MDA, NO and NOS and hepatic indexes, decreases in SOD, GSH and GSH-Px and no notable change in BUN, CR levels and kidney weight/body ratio. Conclusion: The abirritation mechanism of volatile oil of Evodia Fructus was related to the inhibition of pain transmitter release, peroxidative damage and NO damage, which is accompanied by certain hepatotoxicity, mainly mainly oxidative damage, with a concurrent "dose-time-toxicity" relationship.

摘要

目的

初步研究吴茱萸挥发油对小鼠胃寒证模型的镇痛有效剂量范围及机制,探讨其伴随毒性与氧化损伤机制之间的相关性,为阐释效-证-毒相关性提供实验依据。

方法

采用经典热板法,通过灌胃给予小鼠不同剂量的吴茱萸挥发油诱导胃寒证模型,观察其镇痛作用及伴随的毒副作用,并检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、前列腺素E2(PGE2)、一氧化氮(NO)、一氧化氮合酶(NOS)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、尿素氮(BUN)、肌酐(CR)以及肝脏ALT、AST。将小鼠出现的伴随毒性症状记录于毒性反应积分表中。

结果

吴茱萸挥发油灌胃给药后30 min有明显镇痛作用,60 min达效应峰值,存在一定的“量效”和“时效”关系,血清及肝脏ALT、AST水平升高,血清PGE2、MDA、NO、NOS及肝脏指标升高,SOD、GSH、GSH-Px降低,BUN、CR水平及肾重/体比无明显变化。结论:吴茱萸挥发油的镇痛机制与抑制痛递质释放、过氧化损伤及NO损伤有关,且伴随一定肝毒性,主要为氧化损伤,存在“剂量-时间-毒性”关系。

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