吴茱萸不同炮制品致小鼠肝毒性的“量-时-毒”关系研究

The Relationship of “Dose-Time-Toxicity” of Different Processed Products of Evodia rutaecarpa(Juss.) Benth on Hepatotoxicity in Mice

目的比较吴茱萸不同炮制品连续给药15d致小鼠肝毒性的"量-时-毒"关系,探讨吴茱萸的炮制减毒原理。方法将昆明小鼠随机分为正常组和吴茱萸不同炮制品组,各炮制品分为3个不同剂量组,以6.5,3.25,0.65 g·kg^(-1)连续ig 5 d,10 d,15 d后处理,检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)和碱性磷酸酶(AKP)的活性,并计算肝、肾脏器指数,光镜下观察肝组织形态变化。结果与正常组比较,生吴茱萸组可显著升高小鼠肝、肾脏器指数(P<0.01,P<0.05),显著升高小鼠血清中ALT、AST、LDH、AKP的含量(P<0.01,P<0.05),显著增加肝组织病理损伤程度;与生吴茱萸组比较,甘草制吴茱萸组、盐吴茱萸组可明显降低小鼠肝、肾脏指数(P<0.01,P<0.05),显著降低小鼠血清中ALT、AST、LDH、AKP的含量(P<0.01,P<0.05),降低肝组织病理损伤程度。肝、肾脏指数和病理形态学的改变具有时间依赖性,吴茱萸各炮制品致小鼠肝毒性的作用顺序为:生吴茱萸>甘草制吴茱萸>盐吴茱萸。结论给小鼠连续灌胃一定剂量的吴茱萸不同炮制品后,可造成较为显著的肝损伤,毒性呈剂量依赖性,并具一定的肝毒性"量-时-毒"关系,炮制品可降低吴茱萸的体内肝毒性作用。

Objective Objective： To compare the relationship of＂dose-time-toxicity＂induced by multiple dose 15 days of different processed products of Evodia rutaecarpa（Juss.） Benth on hepatotoxicity in mice,and study the attenuation of Evodia rutaecarpa（Juss.） Benth in different processed ways. Methods KM mice were divided into control group and the group of different processed products of Evodia rutaecarpa（Juss.） Benth. The raw products,glycyrrhiza processed products and salt processed products of Evodia rutaecarpa（Juss.） Benth were divided into 3 different dose groups. The different dose groups were given in dose of 6. 5,3. 25,0. 65 g·kg^-1 for 5 days,10 days,15 days and then sacrificed. All animals were determined the content of serum alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,lactate dehydrogenase（LDH） and alkaline phosphatase（AKP）. The liver and kidney index was calculated,and the liver histological changes were investigated. Results Compared with the control group,the raw product group of Evodia rutaecarpa（Juss.） Benth can obviously increase the liver and kidney index of mice（P〈0. 01,P〈0. 05）. Additionally,the activities of serum ALT,AST,LDH and AKP were promoted markedly（P〈0. 01,P〈0. 05） and the damage of liver tissue were increased obviously. Compared with the raw product group of Evodia rutaecarpa（Juss.） Benth,glycyrrhiza processed group and salt processed group can observably decrease the liver and kidney index（P〈0. 01,P〈0. 05）. Moreover,the activities of ALT,AST,LDH and AKP were obviously reduced（P〈0. 01,P〈0. 05）,and improved the liver histological. Furthermore,the liver,kidney index and pathologic change showed time dependence. The toxic effects of different processed products of Evodia rutaecarpa（Juss.） Benth on hepatotoxicity in mice was： the raw product 〉the glycyrrhiza processed 〉the salt processed. Conclusion When the different processed products of Evodia rutaecarpa（Juss.） Benth is given to mice continuously,it may markedly induce liver damage with the increased dose in a dose dependence manner and hepatotoxicity demonstrated by significant time and dose,hepatotoxicity could be reduced by processed.