目的 研究北豆根水提、醇提组分在抗炎作用下伴随出现的毒副作用,为其“功效-毒性”相关性研究提供实验依据.方法 建立复方巴豆油致小鼠耳肿胀和琼脂皮下注射致小鼠肉芽肿模型,分别给不同剂量的北豆根水提、醇提组分连续3天和7天灌胃,观察药物对急、慢性炎症的作用,末次给药后检测血中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性和肌酐(Cr)、尿素氮(BUN)含量,计算肝、肾脏体比值.结果 连续多次给小鼠灌胃北豆根水提、醇提组分可明显抑制巴豆油致小鼠耳肿胀和琼脂致小鼠肉芽肿,随剂量增加,抑制作用增强,呈现一定的剂量依赖关系,且醇提组分肿胀抑制率高于水提组分；水提、醇提组分大鼠血中AST、ALT活性升高,Cr、BUN含量增加,肝、肾脏体比值增大,随剂量增加以上指标变化幅度增大,且肉芽肿模型小鼠的以上指标增加幅度大于耳肿胀模型小鼠,醇提组分对以上指标的增加幅度大于水提组分.结论 北豆根水提、醇提组分在1.2～ 4.7mg· kg-1剂量范围内有明显的抗炎作用,呈现“量-效”关系,随给药时间延长,抗炎作用增强,醇提组分抗炎效果大于水提组分；北豆根水提、醇提组分在1.2～ 4.7mg·kg-1剂量范围内给药3天、7天可对小鼠肝脏产生不同程度的毒副作用,同时北豆根水提、醇提组分在4.2mg· kg-1剂量下给药3天、7天亦可对小鼠肾脏产生不同程度的毒副作用,以上指标具有“量-时-毒”关系变化,且醇提组分对小鼠的肝、肾毒副作用大于水提组分.因此,北豆根的“功效-毒性”具有一定的依赖于剂量和时间的“相关性”,究竟这个“毒性”的作用机制如何？在机制上两者是否也相关？这个“毒性”究竟是严格的“毒性”还是“副作用”均有待于进一步研究证实.%Objective To offer experimental basement for the study of correlation between toxicity and efficacy by researching the toxical and side effects accompanied with anti—inflammation of water and alcohol extract from Rhi— zoma Menispermi. Methods The model of ear swelling by compound recipe of croton oil and granuloma by agar were made and model mice were intragastricaly treated with water and alcohol extract from Rhizoma Menispermi of different doses for 3 and 7 days continually. The anti—inflammatory effect on acute and chronic inflammation was observed. The activities of serum ALT, AST and contents of Cr, BUN were detected while the ratio of liver and kidney to body was measured. Results Both ear swelling by croton oil and granuloma by agar can be inhibited by multiple intragastric administration of water and alcohol extract from Rhizoma Menispermi, and the inhibition rate inhanced with the increase of dosage, showing a certain dependency on dosage. The inhibition rate of alcohol extract is higher than water extract. In mice serum samples of alcohol extract and water extract, the activities of ALT, AST and contents of Cr, BUN increased, and both the ratio of liver and kidney to body enlarged. These above index changed significantly with doses and time. The changes of alcohol extract about these indexes were heavier than water extract. Conclusion Inflammation can be significantly inhibited by both alcohol extract and water extrat in the dosage range of 1.2 to 4.7 mg·kg-1 and show an obvious "dosage—efficacy" relationship. The anti—inflammatory degree increase with the enlarge of dosage, and the effect of alcohol extract is stronger than that of water extract;toxical and side effects of different degree can be caused to liver after administration of the two extracts in the dosage range of 1.2 to 4.7 mg·kg-1 for 3 and 7days; toxical and side effects of different degree also can be caused to kidney after administration of the two extracts of 4.7 mg·kg-1 for 3 and 7 days. All the changesd of these indexes showed obvious "dosage-time-toxicity" relationship and the toxical and side effects caused by alcohol extract is larger than that caused by water extract. Therefore,there is a certain correlation between toxicity and efficacy of Rhizoma Menispermi dependence on the dose and time. However, what the "toxic" mechanism is, Whether the mechanisms between toxicity and efficacy is related, the "toxic" is the strict "toxic" or "side effects" all need to be confirmed by further studies.
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