含马兜铃酸类中药（关木通）毒性成分研究-药物化学专业论文.docx

成都中医药大学硕士学位论文含马兜铃酸中药(关木通)毒性成分研究 成都中医药大学硕士学位论文 含马兜铃酸中药(关木通)毒性成分研究 摘 要 马兜铃属植物在我国作为药用有许多品种，如关木通、马兜铃、青木香等 药材。但近年来，国内外大量报道了马兜铃酸引起的肾脏毒性，因而引起了越 来越多的关注。本文采用现代分析手段，对关木通在配伍前后，其马兜铃酸A 溶出量的变化进行了研究，并对马兜铃酸进行了计算机分子模拟设计，用还原 反应法对马兜铃酸进行了结构改造，比较了马兜铃酸改造前后，对大鼠肾毒性 的影响。结果表明： 1．用HPLC测定了关木通中马兜铃酸A的含量，为5．6897rag／g；比较了关 木通分别与大黄和川芎配伍后，马兜铃酸A溶出量的变化大小，结果为：与大 黄配伍和川芎配伍马兜铃酸A分别降低了34．1％和4．1％，这与文献报道关木通 与大黄等配伍能降低肾毒性，可能有一定的关系。 2．用紫外分光光度法测定了关木通中马兜铃总酸的含量，为15．1m∥g；通 过还原反应将马兜铃酸还原成马兜铃内酰胺。 3．通过大鼠急性肾毒性实验，比较了马兜铃酸改造前后对大鼠急性肾毒性 的各项血、尿生化指标的影响，实验表明：改造后产物对。肾脏的毒性较改造前 有降低的趋势，但无显著的差异。 关键词：马兜铃属马兜铃酸A肾赃毒性配伍分子模拟模型结构 成都中医药大学硕士学位论文ABSTRACT 成都中医药大学硕士学位论文 ABSTRACT Many Chinese-herbs come from the Aristolochiae plants，such as Fructus Aristolchia(FA)A．manshuriensis Kom．(AMK)，A．debilis Sieb．et Zucc(ADS)etc． However,in the recent,more and more people have paid attention to the i11一effect of the induced by Adstolochinc acid(AA)around the world．In our study,we analyzed the quantity of the AA in the AMK．In addition，we analyzed the effect of the quantity of the AA in the AMK when making up wi也Radix et Rhizoma Rhei(RR)or Rhizoma Ligusfici Chuanxiong(RLC)．We have studied the structure—activity relationships of the AA with the molecular imitate techniques．We modified the structure of the AA，and made a comparison between the AA and modified—AA(M-AAl in the nephrotoxicity of the rat．nlc result of experiments showed as below： 1．The AA contents of AMK was 5．6897mg／g by the HPLC．When the AMK made up with the RR the AA contents can be reduced to 34．2％．and the RLC to 4．1％． 2．The total AA contents of AMK was 15．1mg／g by the ultraviolet spectrophotometry．We used the iron as the reductive agent to reduce AA． 3．We made a comparison between the AA and M—AA in the nephrotoxicity of the rat．The result shows：the M—AA Can relieve nephrotoxicity ofthe rat．but it is not markable． Key words：A．manshuriensis Kom．，Aristolochinc acid，nephiotoxicity, structure—activity relationships，molecular imiSate technique，reduction 2 成都中医药大学硕士学位论文前 成都中医药大学硕士学位论文 前 言 随着中药的现代化与国