吴茱萸水提组分镇痛及伴随毒副作用研究

Study on Analgestic Effect and Accompanying Toxicity and Side Effects of Water Extraction Components of Evodia Fructus

目的对吴茱萸水提组分发挥镇痛药效剂量下出现的伴随毒副作用进行观察与研究,为阐明其"功效-毒性"相关性提供实验依据。方法小鼠按体重随机分为5组,即正常对照组、扶他林组、吴茱萸水提组分高、中、低剂量组,连续给药7天,末次药后90min采用小鼠腹腔注射醋酸致痛法及小鼠热板法疼痛模型,观察吴茱萸水提组分对小鼠扭体反应次数及热痛阈值的影响;除观察小鼠毒性症状外,检测血清和肝脏组织谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,以及血清尿素氮(BUN)、肌酐(Cr)含量,计算肝、肾脏器指数,光学显微镜下观察肝组织形态变化。结果连续多次给小鼠灌胃一定剂量的吴茱萸水提组分,可显著减少小鼠扭体反应次数和明显提高小鼠热板痛阈值,且呈现良好的量-效关系;给药期间,小鼠出现腹泻、怠动、烦躁、体重增长缓慢等毒性症状,血清和肝组织内ALT、AST活性均升高,肝体比值明显增大,血清BUN、Cr含量无明显变化,肾体比值只有高剂量组出现增大;上述变化随剂量的增加而逐渐加重,与正常对照组比较有明显差异,呈现一定的"量-毒"关系。结论连续给小鼠灌服一定剂量的吴茱萸水提组分,其在发挥镇痛药效的同时会对肝脏产生一定的毒副作用,并呈现一定的剂量依赖关系。

Objective Researching on the accompanying toxicity and side effects under the efficacy dose of analgestic effect of water extraction components ofEvodia Fructus, to offer experimental basement for the elucidation of ＂efficacy- toxicity＂ relevance. Methods Mice were randomly divided into 5 groups according to weight, namely normal group, diclofanac sodium sustained release tablets group, high, middle and low dose group of water extraction components of Egodia Fructus. Mice were continuously administrated for 7 days, and the analgestic effect of water extraction components of Evoclia Fructus was studied with the pain model in mice induced by acetic acid and hot plate after 90 minutes of the last administration to mice. In addition to observe the toxical symptoms in mice, the activity of ALT and AST in serum and hepatic tissue the content of BUN and CR in serum were detected, and liver, kidney index were detected, and the morphological changes of liver tissue were observed under light microscope. Results By continuously administrating certain dose water extraction components of Evodia Fructus to mice for 7 days, water extraction components of Evodia Fructus could remarkably reduce the frequence of writhe in mice induced by acetic acid and remarkably raise the pain threshold of mice, and there was good dose-efficacy relationship; during the administration, mice had some toxical symptoms, such as diarrhoea, idle move, dysphoria and the slow growth of weight, and the activity of ALT and AST in serum and hepatic tissue were remarkably increased and the liver index was remarkably increased, and the content of BUN and CR in serum had no significant changes, only the kidney index of high dose group was increased; the above-mentioned change gradually aggravated with dose increasing, and it was the obvious discrepancy compared with distilled water control group and there was certain ＂dose-toxicity＂ relationship. Conclusion By continuously administrating certain dose water extraction components of Evocha Frucrus to mice, it could produce certain side effects to liver while it produced the analgestic effect to mice, and showed certain dose-dependence relationship.