中国中药杂志

2016, v.41(09) 1713-1717

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基于Walker256恶性胸水模型的中药甘遂量-毒-效关系研究
Dosage-toxicity-efficacy relationship of Kansui Radix in malignant pleural effusion models based on Walker 256 analysis

沈娟;唐于平;徐远超;开钧;宿树兰;钱大玮;张丽;段金廒;
SHEN Juan;TANG Yu-ping;XU Yuan-chao;KAI Jun;SU Shu-lan;QIAN Da-wei;ZHANG Li;DUAN Jin-ao;Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,Nanjing University of Chinese Medicine;

摘要(Abstract):

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。
To investigate the dosage-toxicity-efficacy relationship of Kansui Radix,explore its regularity of the toxicity and efficacy change,and provide scientific basis for its clinical rational application,the malignant pleural effusion models were used to observe the effect of Kansui Radix with larger dose range( 0. 045 - 1. 620 g·kg·d~(-1)for Kansui Radix) on biochemical indexes and hydrothorax volume in experimental animals. Factor analysis method was also used to comprehensively assess the dosage-toxicity-efficacy relationship of Kansui Radix. The results showed that the rats in model group had larger hydrothorax volume,and ALT,AST,LDH,HBDH,IFN-γ,IL-2 and TNF-α levels were significantly increased( P < 0. 05),while TP and ALB levels were decreased( P < 0. 05) as compared with the blank group. After drug administration,various treatment groups decreased hydrothorax volume,IFN-γ,IL-2,TNF-αand increased TP and ALB levels as compared with model group,indicating certain therapeutic effect; and increased ALT,AST,LDH and HBDH levels,indicating certain liver and cardiac toxicity. In the factor analysis,two common factors were extracted from nine indexes,explaining 89. 1% of the information. The analysis results suggested that there was no obvious toxicity in case of independent use of Kansui Radix within the dosage range set in pharmacopeia,while it would produce liver toxicity and cardiac toxicity upon 3 times of the dosage set in pharmacopeia,and the toxicity was increased with the increase of dose. At the same time,Kansui Radix can decrease the hydrothorax volume in malignant pleural effusion models and improve relevant physical indexes in a dose-dependent manner.Comprehensive analysis results of its toxic effect characteristics indicated that the upper-limit dose of Kansui Radix in pharmacopeia shall be regarded as the relatively optimal therapeutic dose.

关键词(KeyWords): 甘遂;量-毒-效关系;因子分析;恶性胸水
Kansui Radix;dosage-toxicity-efficacy relationship;factor analysis;malignant pleural effusion

Abstract:

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基金项目(Foundation): 国家重点基础研究发展计划(973)项目(2011CB505300,2011CB505303);; 国家自然科学基金项目(81373972)

作者(Author): 沈娟;唐于平;徐远超;开钧;宿树兰;钱大玮;张丽;段金廒;
SHEN Juan;TANG Yu-ping;XU Yuan-chao;KAI Jun;SU Shu-lan;QIAN Da-wei;ZHANG Li;DUAN Jin-ao;Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,Nanjing University of Chinese Medicine;

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