彭文煌 中國醫藥大學
近年來，中藥所致腎臟損害日益受到人們的重視。腎臟是體內藥物的主要代謝和排泄器官，也是藥物毒副作用的主要靶器官。中藥腎毒性已經成為制約中藥現代化和臨床應用的一大障礙。為了確保中藥的安全使用，有必要加強中藥的毒理學研究。然而，中藥製劑在台灣之使用相當普遍，基於政府過往推動之公共衛生概念，關於健康之維護應建立在「防患於未然」，換言之即是「預防勝於治療」；因此，在台灣中藥對腎臟之傷害機制尤其值得作深入之探討。本計畫為常用中藥複方腎毒性之研究，預計進行兩年，將以自健保局臨床常用複方濃縮中藥使用量前100名及中藥常用基準方兩百方中，挑選出尚未進行研究過的複方製劑為主要研究之對象，評估其致肝臟及腎臟毒性。計畫每年分別進行15種複方製劑體外及體內腎毒性試驗評估，預計將進行30種複方製劑。首先進行複方製劑腎細胞株之體外毒性篩選，並進一步進行動物實驗之體內篩選驗證。對於會造成腎臟毒性的中藥複方製劑，則可進一步進行該中藥複方製劑內含之主要成分/指標成分在動物體內之吸收分佈、代謝排泄之藥動學研究，以及腎毒性間劑量-效應關係探討。在活體實驗方面，則是以在體外篩選得知其具有毒害腎細胞之複方中藥或內含主要成分/指標成分，餵食大鼠並收集其血液及尿液進行評估，在腎功能評估方面除進行血清肌酸酐(Creatinine)之分析外，亦依據美國食品藥物管理局(FDA)建議之七種生物標誌物(biomarkers)之分析，來評估複方中藥及其內含主要成分/指標成分對腎之傷害，同時針對腎臟進行組織切片，進行病理分析，以期找出具腎臟傷害特性之複方中藥及其指標成分。本計畫利用篩選腎臟毒性的細胞平台、動物模式及其血及尿中生物標誌物及病理切片方式對30種常用中藥複方製劑進行評估。此研究之進行所建立的相關資訊，相信將有助於促進國人用藥安全，期減少藥物產生腎毒性的危險及減少相關中藥製劑在使用上安全的疑慮。
關鍵詞：腎毒性、中藥製劑、組織切片、生物標記、大鼠、細胞
Nephrotoxicity study on common use TCM prescriptions（2-2）
Wen-Huang Peng School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University
The traditional Chinese medicine (TCM) resulted in kidney injury was valued by day by day. The kidney, the main excretory organ, is also the medicine poisonous side effect main target organ. The TCM kidney toxicity already became the restriction of TCM modernization and a big barrier in clinical practice. In order to guarantee that TCM safety, it is necessary to strengthen the toxicological research of the TCM. However, the TCM preparations are quite common use in Taiwan, based on government passing impetus public health concept, should establish maintenance of the health in “prevents accidents before they occur”, in other words, is “the prevention wins in the treatment”. Therefore, it is worthy of studying the nephrotoxicity of TCM preparations in Taiwan. This plan for studying the nephrotoxicity of commonly used TCM prescriptions take from the first 100 TCM prescriptions of health insurance bureau clinical commonly used prescriptions and 200 basic TCM prescriptions that will not yet carry on. This plan will research the nephrotoxicity of fifteen prescriptions per year in vitro and in vivo for two years. To study nephrotoxicity of fifteen prescriptions on kidney cell line and animals. In order to clarify the relationship of nephrotoxicity of TCM prescriptions and toxic compounds, we will detect the absorption, distribution, metabolism of TCM prescriptions in the blood of animals by using HPLC. The TCM prescriptions possessed nephrotoxicity in vitro will administered to rats for in vivo study. We will collect the blood and urine of rats for analyzing the blood serum creatinine. We also analysis of the seven biological biomarkers based on American Food Medicine Administrative bureau (FDA) suggestion. Finally, we will carry on the pathology analysis. This plan use screening kidney toxic cell platform, the animal pattern and the blood and the urine biomarkers and the pathological section carries on the appraisal to 15 kinds of commonly used TCM prescription preparations. This research establishes the related information which will be helpful in promoting the people to apply TCM prescriptions, the reduction of the kidney toxic danger and the reduced in the use the safe anxiety in TCM preparations.
