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该文考察中药甘遂的量-毒-效关系,探讨甘遂的毒效变化特点,为临床安全合理用药提供科学依据。以恶性胸水模型为研究对象,在较大剂量范围内(甘遂0.045~1.620 g·kg~(-1)·d~(-1))考察甘遂对实验动物生化指标、胸水量等的影响,并通过因子分析方法综合评价甘遂的量-毒-效关系。结果显示,模型组大鼠具有较多的胸水量,且与空白组比较,ALT,AST,LDH,HBDH,IFN-γ,IL-2,TNF-α显著升高(P<0.05),TP,ALB降低(P<0.05)。给药后,与模型组比较,各组可不同程度的减少胸水量,降低IFN-γ,IL-2,TNF-α,升高TP,ALB,体现出一定的治疗作用,同时引起ALT,AST,LDH,HBDH升高,体现出一定的肝、心脏毒性。通过因子分析从9个指标中抽提出2个公因子,共解释了89.1%的信息。结果表明,甘遂在《中国药典》剂量范围内单独给药没有见到明显毒性,在药典高限3倍剂量下可产生肝脏、心脏毒性,随着剂量增加,毒性增强;同时甘遂具有“峻下逐水”功效,可减少恶性胸水模型大鼠的胸水量及改善相关生理指标,且具有剂量依赖性。综合分析其毒效特点,甘遂药典高限剂量为其相对最佳治疗剂量。
This paper investigates the quantity-toxicity-efficacy relationship of Chinese medicine Kansui and explores the change characteristics of Kansui’s toxic effect, providing a scientific basis for clinical safety and rational drug use. In the malignant pleural effusion model, the effect of Kansueryu on biochemical indexes and pleural effusion in experimental animals was investigated in a large dose range (0.045-1.620 g · kg -1 · d -1) , And through the factor analysis method to synthetically evaluate the dose-toxicity-effect relationship of kansui. The results showed that the rats in the model group had more pleural effusion, and the levels of ALT, AST, LDH, HBDH, IFN-γ, IL-2 and TNF-α were significantly higher than those in the blank group (P < ALB decreased (P <0.05). After administration, compared with the model group, each group can reduce the amount of pleural effusion, reduce the levels of IFN-γ, IL-2 and TNF-α, and increase the levels of TP and ALB, , LDH, HBDH increased, reflecting a certain degree of liver and heart toxicity. Factor analysis was used to extract two common factors from nine indicators, explaining a total of 89.1% of the information. The results showed that, Kansui in the “Chinese Pharmacopoeia” dose alone did not see the obvious toxicity, the pharmacopoeia in the high limit of 3 times the dose can produce liver and heart toxicity, with the dose increased, toxicity increased; while Kansui has “Jun under the water” effect, can reduce the malignant pleural effusion of pleural fluid and improve the relevant physiological indicators, and a dose-dependent manner. Comprehensive analysis of its toxic effects, high dose of Kansui Pharmacopoeia dose for the relative best therapeutic dose.