鮑力恒 環球學校財團法人環球科技大學生物技術系

慢性腎功能衰竭目前是全球健康問題中最熱門也最被重視的議題之一，其中，根據統計世界各地罹患慢性腎臟病人口日益增加，使得需要接受腹膜透析、血液透析及腎臟移植之『末期腎臟病患』的人數與日俱增，目前已成為世界各國醫療照護上相當重大的負擔。根據美國國家衛生署以及美國國家衛生研究院比較各國登錄資料統計，台灣尿毒症人口數為世界第一，存活的尿毒症患者（盛行率）比例世界第一，而每年新增病例數（發生率）也是全球第一名。另外，根據台灣腎臟醫學會2006年之統計，目前全台灣透析患者已超過4萬人，而引發尿毒症病因中，慢性腎絲球腎炎（以下簡稱為腎炎）是最常見的一種，約莫佔了38.95％；造成腎炎之主要原因可分為原發性及續發性，在續發性原因中，藥物之濫用是常見因素之一，而常見被濫用之藥物包括有西藥及中藥；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，在台灣中藥製劑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中藥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複方製劑是否具有造成腎毒性的危機。本計畫將以二年時間，每年針對已進行過相關研究過的前20名健保局常用中藥複方製劑和99-100年度執行的30種中藥複方製劑以外，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，進行腎臟細胞株之體外篩選以及動物實驗之體內篩選驗證，對於經篩選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，除此之外，本研究亦會納入代謝體學研究模式進行代謝途徑的探討。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尿素氮與血清肌酸酐之血清生化分析外，亦納入美國食品藥物管理局建議之七種生物標記之分析，來評估複方中藥及其內含主要成分/指標成分對腎臟之傷害，同時針對腎臟進行病理分析，以期找出具腎臟傷害特性之複方中藥及其指標成分。

關鍵詞：腎毒性、中藥製劑、腎臟細胞、大鼠動物模式、生物標記、代謝體學

Study of Nephrotoxicity Induced by Traditional Chinese Medicines Preparation

Li-Heng Pao Department of Biotechnology, TransWorld University

Chronic kidney disease (CKD) is one of the most important public health issues worldwide. 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. Although ESRD patients account for only 0.15% of the total population in Taiwan, we spend more than 7.2% of the annual national health insurance budget to provide them with adequate dialysis and needed care. Therefore, the health care expenditure for ESRD patients has become a huge burden in our society and is worthy to attention. Facing these unprecedented challenges, we have to delineate the complicated mechanisms of ESRD to slow its progression or to prevent it from occurring. The misusing of drugs, especially, the Chinese herbal medicines, is one of the major factors we can control to reduce the ESRD. Thus, the main purpose of this two-year proposal is to explore the nephrotoxicity of top 100 Chinese herbal medicines (CHMs) used in Taiwan. The selected most commonly used 10-15 CHMs and their major components will be studied for every year. The nephrotoxicity will be firstly evaluated using renal cell lines in vitro. Possible candidates from the in vitro study will be further evaluated in the Sprague-Dawley rats’ animal study in vivo using the serum biochemistry (BUN and creatinine), seven biomarkers recommended by the US FDA, and histopathological evaluation of kidney biopsy. Besides, the emerging metabolomics will also be used to investigate the possible nephrotoxic mechanisms in this proposal. Not only will the nephrotoxicity of popular Chinese medicines be evaluated, but the screening platform of nephrotoxicity of drugs will also be constructed by this project. 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.