常用中藥製劑對於腎臟致毒性之研究

鮑力恆
國防醫學院
末期腎臟病目前已成為世界各國醫療照護上重大的負擔，根據美國國家衛生署（USRDS）比較各國登錄資料統計，台灣尿毒症人口數為世界第一。；造成腎炎之主要原因中，藥物之濫用是常見因素之一，然而中藥製劑在台灣之使用相當普遍，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。本研究將以自健保局臨床常用複方濃縮中藥前100名中挑選出尚未進行研究過的10-15種複方製劑及其內含主要成分/指標成分作為主要研究之對象，以評估國人常服用之中藥製劑是否具有腎傷害的危機。本計畫將以二年時間，每年針對健保局常用中藥複方製劑前20名(已進行過相關研究)以外的方劑中挑選出使用較多之10-15種方劑以及其內含主要成分/指標成分，進行腎細胞株之體外篩選以及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)建議之七種生物活性因子(biomarker)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。
關鍵字：腎毒性、中藥製劑、組織切片、生部標記、大鼠、細胞

Study of Nephrotoxicity Induced by Traditional Chinese Medicines Preparation

Li-Heng Pao
National Defense Medical Center
In Taiwan, the number of patients with end-stage renal disease (ESRD) is steadily increasing. According to the USRDS (the US Renal Data System) annual report in 2006, the incidence and prevalence of ESRD patients in Taiwan ranked the highest in the world. Health care expenditure for ESRD patients has become a huge burden on our society. The misusing of drugs, including the Chinese herbal medicines(CHMs), is one of the major factors that could lead the ESRD. Thus, the main purpose of this study is to explore the nephrotoxicity of 10-15 CHMs and their major components from top 100 CHMs used in Taiwan. The in vitro nephrotoxicity will be evaluated using various kidney cell lines. Possible candidates from the in vitro study will be further evaluated in the animal study using the 7 biomarkers recommended by the US FDA to assess the level of creatinine in rat urine. Biopsy of kidney will also be performed for the histopathological evaluation. This project will provide the evidences bases to properly regulate the usage of Chinese herbal medicines prevent the misusing of Chinese herbal medicines and eventually reduce the incidence and prevalence of ESRD in Taiwan.
關鍵字：nephrotoxicity, Chinese herbal medicines, , SD-rat, cell lines