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吴茱萸挥发油对大鼠长期毒性实验研究

Study on Chronic Toxicity of Volatile Oil from Evodia Fructus in Rats

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【作者】 尹利顺吕莉莉龚彦胜李晓宇黄伟孙蓉

【Author】 YIN Li-shun;LV Li-li;GONG Yan-sheng;LI Xiao-yu;HUANG Wei;SUN Rong;Shandong Academy of Chinese Medicine;Shandong University of Traditional Chinese Medicine;

【机构】 山东省中医药研究院山东中医药大学

【摘要】 目的连续观察35天给大鼠吴茱萸挥发油导致大鼠长期毒性损伤程度及恢复情况。方法分别给大鼠灌胃高、中、低剂量的吴茱萸挥发油连续35天,按生药量计算,分别为0.12,0.06,0.012 m L·kg-1·d-1,除观察一般状况外,检测血常规、血清肝功能、肾功能、脂质代谢、糖代谢相关指标,处死大鼠,称取心、肝、脾、肺、肾脏质量,计算脏、体比值,进行肝脏病理组织学检查。剩余大鼠停止给药,恢复20天,观察大鼠恢复情况,并进行上述相同指标的检测。结果不同剂量的吴茱萸挥发油在连续给药35天后可导致大鼠体重下降,饮食、饮水不佳,导致血中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST),碱性磷酸酶(ALP)、总蛋白(TP)水平明显增高,白蛋白(ALB)明显降低,白蛋白/球蛋白(A/G)降低,肝脏质量和肝体比值增大,病理学检查可见不同程度的肝组织损伤;上述变化随剂量的增加而逐渐加重,与空白组比较有明显差异。对总胆红素(TBI)、尿素氮(BUN)、肌酐(Cr)、血糖(Glu)、胆固醇(CHO)等指标和血常规影响不明显;肝毒性损伤程度与用药剂量呈一定的剂量依赖相关性。恢复期大鼠各剂量组ALT指标与空白组比较有不同程度显著性,高剂量组AST与空白对照组比较有显著性差异,其余指标未见显著性差异。结论长时间给予一定剂量的吴茱萸挥发油可造成大鼠明显的蓄积毒性,其毒性损伤部位以肝损伤为主,经过20天恢复期观察,其脏器损伤基本可恢复。

【Abstract】 Objective To observe the chronic toxicity damage and convalescence of the volatile oil components from Evodia Fructus in rats. Methods The volatile oil components with different doses from Evodia Fructus were separately orally given to rats, and the high, middle and low lose-group were separately 0.12, 0.06, 0.012 m L·kg-1·d-1calculated by crude herbs. Besides the general conditions were observed,the related indexes were detected, such as the routine control of blood,hepatic function,renal function,the metabolism condition of lipids and the glycometabolism indexes.The rats were dissected and the weight of heart, liver, spleen, lung, kidney, were precisely weighed and calculated the ratio of organ to body. The histopathologic examination of hepatic tissue was carried out. The remaining rats were not administrated, and recovered for 20 days, the recovery conditions of rats were observed, and the above indexes were also detected. Results The volatile oil components from Evodia Fructus with different doses could induce the body weight decreasing in rats,the level of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP)and total protein(TPC) serum obviously increased, albumin(ALB) and the ratio of ALB to GLB in serum obviously decreased, the liver weight and the ratio of liver to body increased, and the hepatic tissue damage was obvious in the histopathologic examination of hepatic tissue. The above-mentioned changes gradually aggravated with dose increasing, and there was no obvious difference compared with control group. The influence on the content of total bilirubin(TBI), blood urea nitrogen(BUN), glucose(GLU), total cholesterol(CHO) and creatinine(Cr)was not obvious, and the hepatic toxicity degree had certain dose dependence relatonship. Except the ALT level of different doses group in the above indexes of recovered rats had significant difference compared with control group,as well as the AST level of high dose group also had significant difference, the other indexes had no significant difference.Conclusion The long term administration of volatile oil components from Evodia Fructus at certain dose in rats could induce obvious cumulative toxicity, and the mainly toxical injury sites were in liver, but after recovery period observation, the live injury was basically recovered.

【基金】 国家重点基础研究发展计划(973)中医基础理论专项资助项目(2009CB522802);山东省科技平台建设项目课题(2008GG2NS02021)
  • 【文献出处】 中国药物警戒 ,Chinese Journal of Pharmacovigilance , 编辑部邮箱 ,2015年01期
  • 【分类号】R285.5
  • 【被引频次】17
  • 【下载频次】521
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