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期 刊 ：中国中药杂志 2005年 30卷 13期 页码：1019.

关键词：关木通；马兜铃酸；急性毒性；肾毒性；

Keywords:Aristohchia, manshuriensis, aristolochic acids, acute toxicity, nephrotoxicity,

摘 要 ：目的:以马兜铃酸A为剂量标准比较了关木通醇提物和关木通马兜铃总酸对小鼠的急性毒性,探讨关木通致毒的剂量关系。方法:小鼠单次灌胃关木通醇提物及其马兜铃总酸后,测定LD₅₀、肝、肾功能及观察了肝、肾组织形态学变化。结果:小鼠给予关木通醇提物的LD₅₀值为4.4g·kg^-1,折合成马兜铃酸A为40mg·kg^-1,与小鼠灌胃给予马兜铃总酸后的LD₅₀值(折合成马兜铃酸A为♂33mg·kg^-1,♀37mg·kg^-1)相近。给予关木通醇提物剂量折合成马兜铃酸A为4.5mg·kg^-1以上时,可引起血尿素氮和肌酐水平增高,同时可见肾脏组织形态学改变;折合成马兜铃酸A25mg·kg^-1以上时可引起AST增高和肝脏组织形态学改变;以上病变程度均与马兜铃酸A的剂量成正比。结论:关木通除了有明显的肾脏毒性外,还有肝脏毒性,致肾毒剂量较致肝毒剂量低,肾脏毒性是关木通致死的主要原因,马兜铃酸是主要的致肾毒成分。关木通的致死和致肾毒作用与马兜铃酸A的剂量成正比例。

Abstract:Objective: The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined. Method: A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD₅₀ values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice. Result: LD₅₀ value of GMT extract was 4.4 g·kg^-1 which was equivalent to 40 mg·kg^-1 as calculated by the content of AA in GMT extract, and this value was comparable with LD₅₀ obtained from TA given intragastrically in mice (equivalent to 33 mg·kg^-1 of AA for male and 37 mg·kg^-1 for female) . GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg·kg^-1 and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg·kg^-1 and above. All changes were in proportion to the doses of AA. Conclusion: GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.

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