从药代-药效方面研究乳移平配伍桔梗方剂抗乳腺癌肺转移的药效物质基础

The curative effect of empirical formula Ruyiping Formula and Platycodon grandiflorum in clinic to prevent lung metastasis in breast cancer patients is clear,but the material basis of its function has not been able to clarify all the time. Invariably the material basis of chinese herbal formulas stresses the effective components which is relevant with the drug efficacy. Guided by traditional Chinese medicine theory,In order to verify the active ingredients of Ruyiping Formula and Platycodon grandiflorum on lung metastasis, the mice with lung metastasis of breast cancer model will be used in our study. On the basis of earlier -clinic and experiment, the PK-PD associated analysis model will be used to analyze the association of the effects of Ruyiping and its metabolites with their constituents in the mice with lung metastasis .The concentration of Ruyiping and Platycodon frandiflorm in samples will be measured and the effects of Ruyiping and platycodon frandiflorm on lung metastasis will be quantified by pharmacology indexes. The relationship of the concentrations of Ruyiping formula and Platycodon frandiflorm with inhibitory rate in plasma, lung and tumor will be analyzed comprehensively. Based on the results, the "concentration-effect-time" model will be simulated to analyze the real relationship of effects of Ruyiping Formula and Platycodon grandif lorum with their active ingredients in metastatic breast cancer. The research findings will provide the foundation for further development of Ruyiping Formula and Platycodon grandiflorum and also supply an approach for the study of the active ingredients in Traditional Chinese Medicine formulation with PK-PD method.

抗乳腺癌复发转移的临床经验方乳移平配伍肺经引经药桔梗组成的方剂治疗乳腺癌肺转移的临床疗效明确，但其作用的物质基础始终未能阐明。中药复方的物质基础历来强调的是与其药效相结合的的有效组分，本项目以中医理论为指导，以阐明乳移平配伍桔梗方剂治疗乳腺癌肺转移的活性物质基础为目标，在前期临床和实验的基础上，通过对方剂的药代动力学和药效学研究，探讨进入血液和肺脏的乳移平配伍桔梗方剂主要化学组分及其代谢产物与预防乳腺肿瘤肺转移等效应之间的相互关联性，寻找能够良好拟合"浓度-效应-时间"模型的真正效应物质，为乳移平配伍桔梗方剂发展成为治疗乳腺癌肺转移的新型中药复方药物奠定基础，同时也为中药复方药效物质基础研究提供新的思路。

抗乳腺癌复发转移的临床经验方乳移平配伍肺经引经药桔梗组成的方剂治疗乳腺癌肺转移的临床疗效明确，但其作用的物质基础始终未能阐明。本项目通过对方剂的药代动力学和药效学研究，探讨进入血液和肺脏的乳移平配伍桔梗方剂主要化学组分及其代谢产物与预防乳腺肿瘤肺转移等效应之间的相互关联性，寻找能够良好拟合“浓度-效应-时间”模型的真正效应物质，为乳移平配伍桔梗方剂发展成为治疗乳腺癌肺转移的新型中药复方药物奠定基础，同时也为中药复方药效物质基础研究提供新的思路。.我们选用小鼠乳腺癌高肺转移细胞4T1建立乳腺癌肺转移动物模型，接种后观察成瘤情况，并用乳移平配伍桔梗方剂进行干预。将小鼠分为空白组、模型组（灌胃给予生理盐水）、阳性组（灌胃给予乳移平方剂水煎液）和治疗组（灌胃给予乳移平配伍桔梗方剂水煎液）四组，空白组5只，模型组10只，阳性组和治疗组各36只，每天给药一次。比较四组小鼠的原位瘤生长情况，给药15天开始每5天体外测量小鼠瘤块长短径，给药22天后分时间点进行眼眶采血，取出肿瘤组织和肺组织。以瘤体积、瘤重、肺重等指数作为药效评价指标，研究乳移平配伍桔梗方剂对肿瘤的抑制作用。收集血浆、肺组织样本，通过多种液质联用手段明确乳移平配伍桔梗方剂进入血液系统及肺脏的化学物质群，应用IMS图像分析系统和Photoshop CS5对各组小鼠肺转移灶进行定量分析，研究乳移平配伍桔梗方剂对乳腺癌肺转移的抑制作用。.和模型组平均瘤重相比，阳性组和治疗组平均瘤重明显较低，根据公式 抑瘤率（%）=（空白模型组平均瘤重－实验组平均瘤重）/空白模型组平均瘤重×100%可算得治疗组抑瘤率，25.32%（p<0.05），确认乳移平配伍桔梗方剂对肿瘤有抑制作用。.实验结果表明乳移平配伍桔梗方剂对肿瘤生长有良好的抑制作用，而对癌细胞肺转移的抑制情况需要进一步探索，其抑制肿瘤生长的物质基础是中药方剂发挥药效的关键所在，也需要进一步探索，这些将作为后续研究的主要内容。