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, Nanjing 210023, China.
Zhongguo Zhong Yao Za Zhi. 2016 May;41(9):1713-1717. doi: 10.4268/cjcmm20160923.
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-α and 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.
为探讨甘遂的量-毒-效关系，探寻其毒性与药效变化规律，为临床合理应用提供科学依据，采用恶性胸腔积液模型观察较大剂量范围（甘遂0.045 - 1.620 g•kg•d⁻¹）甘遂对实验动物生化指标及胸腔积液量的影响。同时采用因子分析法综合评价甘遂的量-毒-效关系。结果显示，与空白组相比，模型组大鼠胸腔积液量增多，ALT、AST、LDH、HBDH、IFN-γ、IL-2及TNF-α水平显著升高（P<0.05），而TP和ALB水平降低（P<0.05）。给药后，各治疗组与模型组相比，胸腔积液量、IFN-γ、IL-2、TNF-α降低，TP和ALB水平升高，表明有一定治疗作用；ALT、AST、LDH及HBDH水平升高，表明有一定肝毒性和心脏毒性。因子分析中，从9项指标中提取出2个共同因子，解释了89.1%的信息。分析结果提示，甘遂在药典规定剂量范围内单独使用时无明显毒性，而当剂量达到药典规定剂量的3倍时会产生肝毒性和心脏毒性，且毒性随剂量增加而增大。同时，甘遂可使恶性胸腔积液模型大鼠胸腔积液量减少，并呈剂量依赖性改善相关生理指标。对其毒性效应特征综合分析结果表明，药典中甘遂的上限剂量可视为相对最佳治疗剂量。
