基于胃寒证吴茱萸水提物镇痛及伴随毒副作用机制.docVIP

基于胃寒证吴茱萸水提物镇痛及伴随毒副作用机制 　　[摘要]对吴茱萸水提物在胃寒证小鼠模型上镇痛作用的药效剂量范围及机制进行初步研究。制备胃寒证小鼠模型，采用经典的小鼠热板法，灌胃不同剂量吴茱萸水提物，观察其镇痛及伴随毒副作用，检测血清ALT，AST，PGE2，NO，NOS，MDA，SOD，GSH，GSH-Px，BUN，CR及肝脏ALT，AST;并通过相关的毒性反应积分表，记录小鼠的伴随毒性症状。吴茱萸水提物在药后30 min有明显的镇痛作用，60 min达到峰效应，呈现一定的“量-效”和“时-效”关系，血中和肝内 ALT和AST水平升高，血中PGE2，MDA，NO，NOS水平的增高，SOD，GSH，GSH-Px水平下降，BUN，CR水平无明显变化，肝体比值增加，肾体比值无明显变化。吴茱萸水提物发挥镇痛效应的机制与抑制疼痛介质释放、过氧化损伤及NO损伤有关;在发挥镇痛效果的同时还会伴随着对肝脏产生一定的毒性，毒性机制主要为氧化损伤，呈现与肝毒性损伤相并行的“量-时-毒”关系。 　　[关键词]吴茱萸;水提物;小鼠;胃寒证;镇痛;毒副作用 　　Study on efficacy accompanied by side effects of water extraction 　　components of Evodiae Fructus based on syndrome model 　　LI Xiao-yu， SUN Rong* 　　（Shandong Academy of Chinese Medicine， Ji′nan 250014， China） 　　[Abstract]The range of effective dose and mechanism of abirritation about water extraction components of Evodiae Fructus on the stomach cold syndrome model in mice were preliminary studied. The method of stomach cold-syndrome model in mice was built， which were administrated with different doses water extraction components of Evodiae Fructus， observing abirritation and toxicity by the classical hot plate method， detecting the level of ALT， AST， PGE2， NO， NOS， MDA， SOD， GSH， GSH-Px， BUN， CR in serum and ALT， AST in hepatic tissue， and recording toxicity symptoms in mice according to the list of relevant toxicity reaction.The water extraction component of Evodiae Fructus has obvious analgesic action after administration 30 min， arriving peak effect after administration 60 min， showing certain ″dose-time-toxicity″ relationship. ALT and AST levels in mice serum and liver tissue enhanced; PGE2， MDA， NO， NOS enhanced in mice serum; SOD， GSH， GSH-Px reduced; the BUN， CR levels was no significant alteration; liver weight/body weight enhanced; kidney weight/body weight was no significant alteration. The a irritation mechanism of volatile oil of Evodiae Fructus was connected with suppressing pain transmitters release， per oxidative damage mechanism and NO damage， which also induced hepatotoxici