基于燥性表征-化学成分关联的“凤眼片枳壳”炮制机理研究

Dry nature is the basic characteristics of Chinese Medicines，which can influence .the clinical application and medicine treatment . Fructus aurantii has the functions of invigorating Qi and Xiaozhang， but because of dry nature large, not suitable for clinical medication. Stir - fried with bran can reduce the dry nature, Zhang FengYan Fructus aurantii can depress the dry nature futher, its has been verified in clinic, but the processing mechanism is not clear. In the research of processing in the past, more attention to was focused on the nourishing, invigorating spleen, but less was to dry nature. This project will execute under the guidance of Chinese medicine theory, using inter-disciplinary research methods and modein technology, with "spleen" and "dry" dual pharmacological activity standards as a guide. The Quantitative change and qualitative change will investigateis comprehensively and systematicly along with the different polar parts of Fructus aurantii Praeparata processed before and after , we hope to get the relationship between this change and dry nature magnitude, and clear the drymonomer or component groups, to determine the effect of Eichhornia piece main material basis of Fructus aurantii dry weakened; and correlation of parameters of processing technology of Fructus aurantii eye piece and pharmacodynamics, processing mechanism of comprehensive interpretation of Eichhornia piece of trifoliate orange shell.

燥性是中药性能特征之一，是影响中药临床应用、指导中药治病的主要理论依据之一。枳壳具理气宽中，行滞消胀等功效，但因生品燥性较大，不适合临床用药。麸炒可缓和燥性，而樟帮凤眼片枳壳因多了自然陈放发酵的步骤，其燥性较药典法枳壳更低，其作用在临床上已被验证，但炮制机理尚不清楚。在以往的炮制研究中，考察健脾作用的指标较多，而燥湿作用指标未见报道，而燥性的大小是制约枳壳药效和副作用的关键指标之一，不可忽视。本课题拟在中医药理论指导下，通过多学科交叉，采用现代研究方法，以"健脾"和"燥性"双重药理活性标准为向导，较全面、系统地研究枳壳饮片炮制前后不同极性部位的量变和质变规律，以及该变化与燥性强弱的关系，明确燥性部位和燥性单体或成分群，确定影响凤眼片枳壳燥性减弱的主要物质基础；并对凤眼片枳壳的炮制工艺参数与药效的相关性进行研究，综合阐释凤眼片枳壳的炮制机理。

燥性是影响中药临床应用、指导中药治病的主要理论依据之一。枳壳麸炒可缓和燥性，而凤眼片枳壳因多了自然发酵的步骤，临床上认为其燥性较药典法枳壳更低，但炮制机理尚不清楚。本课题进行了枳壳不同炮制品健脾、燥性强弱比较研究；枳壳药典法与凤眼片生品不同部位燥性强弱比较研究；枳壳药典法与凤眼片生品化学成分比较研究；凤眼片枳壳燥性化学成分分离；凤眼片枳壳燥性化学成分确证及炮制方法的规范化研究。.结果显示：①实验结果得出凤眼片与药典法枳壳片醇提物均可改善功能性消化不良大鼠的体重、食量、小肠推进率、GAS、MTL、VIP水平及胃组织的轻度炎症，凤眼片在部分指标上相当或优于枳壳片。②全药醇提物整体动物实验的饮水量、全血液黏度及颌下腺AQP5含量均显示，“凤眼片枳壳”比药典法饮片显示更弱的燥性，其中饮水量、颌下腺AQP5含量高低剂量组（P<0.01）。③综合枳壳分部位的整体动物实验饮水量、小鼠颌下腺AQP5含量等考查指标结果，得出燥性较强的部位为乙酸乙酯部位、二氯甲烷部位。枳壳分部位的人颌下腺细胞AQP5mRNA基因表达实验确证了二氯甲烷、乙酸乙脂部位燥性更强，这与整体动物燥性结果一致；急性毒性实验结果显示凤眼片生品挥发油无毒（LD50为6478.46mg·kg-1），药典法生品挥发油有低毒（LD50为4234.38mg·kg-1）。④综合枳壳全药、分部位的整体动物及细胞实验结果，并经颌下腺细胞的AQP5mRNA表达及AQP5蛋白表达实验确证3′,4’,3,5,6,7,8-七甲氧基黄酮等为凤眼片枳壳主要燥性活性成分。⑤规范了凤眼片枳壳炮制工艺。.关键数据：①结合成分、药效与分子生物学阐释“凤眼片枳壳”缓燥炮制机理。②发表心论文11篇，其中中文核心10篇，SCI论文1篇。③培养硕博研究生共2名。.科学意义：从燥性改变角度阐述“凤眼片枳壳”的炮制机理，有利于传承和发扬江西樟帮传统炮制文化技术，规范特色炮制工艺。为进一步开发樟帮特色精品炮制饮片新品种具有重大意义。