基于响应面设计的呼吸道抗炎方剂优化

Optimization of Anti-inflammatory Medication for Respiratory Diseases Based on Response Surface Design

通过将经典的治肺方剂(桔梗汤和桑菊饮)相结合,以基于细胞水平的抗炎作用为评价指标,采用单因素试验筛选得到基本方中各单味药的浓度范围,随后通过Plackett-Burman设计,找出复方中对抗炎效果贡献最大的三味药,即甘草、桑叶和陈皮。在此基础上,通过Box-Behnken试验结合响应面法预测各单味药的最优浓度配比,得到可抑制雾霾引起的呼吸系统炎症的辛凉解表的优化中药复方。最终确定的各味药最佳浓度配比为:甘草3.3×10^(-4) g/ml,桔梗1.0×10^(-4) g/ml,桑叶1.0×10^(-4) g/ml,菊花1.0×10^(-5) g/ml,陈皮1.0×10^(-3) g/ml,在此条件下的炎症抑制率为(46.14±2.62)%。小鼠体内试验表明,该中药复方对混合烟熏模拟雾霾环境诱导的血清和肺组织中肿瘤坏死因子-α和白介素-8的表达水平增加有抑制作用,且呈现出剂量依赖特性。

This experiment combined two classical Chinese patent medicines for puhnonary treatment, Jiegeng decoction and Sangju decoction, to screen a new compound Chinese herbal preparation. The concentration range of the extract of each single herb in this preparation was obtained by single factor test with the anti-inflammatory effect at cellular level as the index. Then the top three most effective herbs were found by Plackett-Burman design, namely Nardostachyos Radix et Rhizoma, Mori Follum and Citri reticulatae Pericarpium. Box-Behnken experiment combined with response surface method was carried out to predict the optimal concentration of each herb extract. The final concentrations were as bllows： Nardostachyos Radix et Rhizoma 3.3× 10^4 g/ml, Platycodonis Radix 1.0×10^4 g/ml, Mori Follum 1.0×10^4 g/ml, Chrysanthemi Flos 1.0×10^-5 g/ml and Citri reticulatae Pericarpium 1.0×10^3 g/ml. The inflammatory inhibition rate of the optimal preparation was （46.14±2.62）%. The results of the in vivo experiment demonstrated that the Chinese herbal compound showed a dose-dependent characteristics in inhibiting the increase of expression of tumor necrosis factor-or （TNF-α） and interleukin-8 （IL-8） in the serum and lung tissue of mice induced by the mixed smoky simulated smog environment, compared with the model group.