基于均匀设计的祛湿化瘀复方抗脂毒性作用的主效应中药分析

目的 观察祛湿化瘀复方的主效应中药或不同组合对游离脂肪酸（free fatty acid, FFA）诱导人肝癌细胞株（HepG2）细胞脂肪沉积和肿瘤坏死因子α（turmor necrosis factor α, TNF-α）分泌的作用，探索中药复方药理作用相应物质基础的分析方法。方法 采用FFA诱导HepG2细胞脂肪沉积和TNF-α分泌的体外细胞模型和药物血清技术，运用数学模型“均匀设计法”，根据复方中的5味中药（茵陈、栀子、虎杖、田基黄、姜黄），选用U11(1110) 表进行组方设计所得10种中药组合进行干预，以对甘油三酯（triglyceride, TG）及TNF-α的抑制效应作为考察指标，筛选主效应中药或组合，并重新区间分组验证。结果茵陈和田基黄在高剂量组合时有显著降低细胞TG及TNF-α含量的效应，与全方比较差异无统计学意义，其中单用茵陈也可显著降低细胞TG及TNF-α含量。结论 茵陈及其与田基黄的组合是祛湿化瘀复方抑制FFA诱导HepG2细胞脂肪沉积和TNF α分泌作用的主效应中药；应用均匀设计与药效学分析的方法可有效分析中药复方针对某一作用环节的主效应中药或组合。

Analysis Depending Uniform Design on the Major Herbs in Qushi Huayu Compound for Anti-hepatic Lipo-toxicity

OBJECTIVE: To analyze the major herbs in Qushi Huayu Compound (QHC) or its various assembles on the fatty deposition and tumor necrosis factor-alpha (TNF-alpha) secretion induced by free fatty acid (FFA) of human hepatic cancer cell line (HepG2) in vitro, for investigating the analytic methods in seeking the basic material in Chinese compound relevant to the pharmacological effect. METHODS: The HepG2 cellular model of fatty deposition and TNF-alpha secretion induced by FFA and seropharmacological technique were adopted. Taking triglyceride (TG) and TNF-alpha inhibitory effect as the indexes of investigation, the effects of 10 combinations assembled by uniform design U1(11) (11(10)) form with drugs chosen from the five herbs in the QHC (oriental wormwood, cape-jasmine fruit, giant knotweed rhizome, Japanese St. John's wort herb and curcuma) were screened to seek the major herbs or optimal combination, which were then validated by grouping in interval. RESULTS: High dosage combination of oriental wormwood and Japanese St. John's wort herb remarkably reduced the TG and TNF-alpha content in the model cells, with the effect insignificantly different from the whole compound. Moreover, single use of oriental wormwood showed a similar effect. CONCLUSION: Oriental wormwood and its combination with Japanese St. John's wort herb are the major herb/optimum combination in QHC for inhibiting fatty deposition and TNF-alpha secretion in hepatic lipo-toxicity model. The major herb or optimal combination in a certain Chinese compound acted on some sticking point could be discovered by adopting uniform design and pharmacodynamics analytic technique.