基于血清药物化学与血清药理学的蒙药肋柱花抗D-GlaN致急性肝损伤药效物质基础研究

Mongolian medicine Lomatogonium carinthiacum is a characteristic of Mongolian drug, with anti liver injury, normalizing gallbladder to cure jaundice, inhibit liver fibrosis,the field in the treatment of liver diseases has broad application prospects，.Based on the characteristics of drug clinical application, this topic focuses on the "material basis" of the biological effects of drug action on the biological effects of drug action in vivo. By serum pharmacochemistry and serum pharmacology method of Mongolian medicine Lomatogonium anti D-GalN induced acute liver injury of pharmacodynamic material basis. The injury induced by D-GlaN in rat primary hepatocytes as the research objectas the Mongolian medicine Lomatogonium carinthiacum of aqueous extract for the example drugs, analysis of Mongolian Lomatogonium injury in rat serum transitional components in acute liver and identify its structure,Based on the application of in vitro, the D-GlaN induced injury of rat hepatocytes cell as the research object to the Mongolian medicine containing Lomatogonium serum and serum transitional components as the example drugs,Compared with Mongolian Lomatogonium serum and serum transitional components to protect the liver cell damage strength, To explore the Mongolian medicine Lomatogonium chemical components, and disease status and biological effect between inner link, determine Mongolian medicine Lomatogonium anti D-GalN induced acute liver injury of pharmacodynamic material basis.This study may lay a theoretical foundation for development leads to the discovery of new compounds and replace the Mongolian medicine active ingredient combination drugs.

肋柱花是特色蒙药，具有抗肝损伤、利胆退黄、抗肝纤维化作用，在肝病治疗领域有广阔的应用前景。本课题从药物临床应用特点出发，围绕“体内化学成分是药物作用于机体疾病状态的、与药物直接相关的生物效应的物质基础”假说。应用血清药物化学与血清药理学方法，探讨蒙药肋柱花抗D-氨基半乳糖胺（D-GlaN）致急性肝损伤药效物质基础。即以D-GlaN致急性肝损伤大鼠为研究对象、以肋柱花水提物为示例药物，分析肋柱花在急性肝损伤大鼠血清中的移行成分并对其进行结构鉴定，进而血清药理学与体外实验，以D-GlaN致损伤大鼠原代肝细胞为研究对象、以含肋柱花血清及血清移行成分为示例药物，比较含肋柱花血清及血清移行成分的保护损伤肝细胞强度，探讨肋柱花体内化学成分-疾病状态-生物效应之间的内在联系，确定肋柱花抗D-GlaN致急性肝损伤药效物质基础。本研究可能对新化合物的发现及代替蒙药的有效成分组合新药的开发奠定理论基础。

研究背景：. 蒙药肋柱花具有平息“协日”和清热功效，在蒙医临床上具有长期治疗肝胆疾病的历史，疗效非常确切。课题组前期实验研究发现，蒙药肋柱花可以明显保护急性肝损伤，并对乙肝病毒（HBV）的DNA复制有一定抑制作用，体现了蒙药肋柱花在急性肝损伤和病毒性肝炎的治疗上具有非常重要的使用价值和实际意义。.研究内容：. 1. 蒙药肋柱花水提物及肋柱花石油醚加乙醇提取部位的抗D-GlaN 致急性肝损伤作用及作用机制研究。. 2. 蒙药肋柱花水提物在D-GlaN致急性肝损伤大鼠血清中移行成分研究。. 3. 蒙药肋柱花抗D-GlaN致肝细胞损伤作用及CCl4致大鼠肝星形细胞损伤作用研究。.结果：. 1. 肋柱花水提物及石油醚加乙醇提取部位均具有抗D-GlaN致急性肝损伤的作用。肋柱花水提物可以降低血清中TNF-α、IL-6水平，增加血清中IL-10、GSH-PX和SOD水平，降低肝组织中MDA含量。提示肋柱花的保肝作用可能是通过抗氧化和抑制炎症因子的表达来实现的。. 2.肋柱花水提物在D-GlaN致急性肝损伤大鼠血清中存在8个血中移行成分，其中1个成分是肋柱花的原型成分—獐牙菜苦苷，其它7个成分均为肋柱花的体内代谢物。以上8个血中移行成分可能是肋柱花化学成分的体内作用形式，也最有可能成为肋柱花的抗急性肝损伤的药效物质基础。. 3. 肋柱花含药血清、肋柱花的血清移行成分—獐牙菜苦苷以及肋柱花水提物均有不同程度的抗D-GlaN致L-02细胞损伤和抗CCl4致HSC-T6细胞损伤作用，肋柱花含药血清的保肝活性比獐牙菜苦苷、肋柱花水提物强，说明肋柱花的保护肝脏作用除了獐牙菜苦苷外，可能还与其它移行成分（代谢物）有关。.科学意义：. 本项目的研究结果可为蒙药肋柱花的进一步推广应用及开发利用提供可靠的实验数据。同时也为更多保肝蒙药的研究提供一定的参考。