رسالة جامعية
Effect of Chinese herbal medicine on renal toxicity
| العنوان: | Effect of Chinese herbal medicine on renal toxicity |
|---|---|
| العنوان البديل: | 複方濃縮中藥製劑對於腎毒性之研究 |
| المؤلفون: | Liu, Jing-Wen, 劉靜雯 |
| مرشدي الرسالة: | Pao, Li-Heng, 鮑力恒 |
| سنة النشر: | 2013 |
| المجموعة: | National Digital Library of Theses and Dissertations in Taiwan |
| الوصف: | 101 中文摘要 近年來，中藥所致腎臟損害日益受到人們的重視。多數藥物吸收後，主要經腎小球濾過、近曲小管分泌、遠曲小管重吸收和小管上皮細胞降解等代謝過程排出體外。在這一過程中均可累積腎毒性而發生結構和功能改變，導致腎臟損傷。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，因此中藥對腎臟之傷害機制尤其值得作深入之探討。 研究發現馬兜鈴(Aristolochia)會造成腎臟損害，但中藥是否仍含其他成分會導致腎毒性，目前我國僅有少數相關文獻與研究。因此本篇研究目的為，挑選出使用較多之複方濃縮中藥，每種複方濃縮中藥選自三家藥廠之產品，主要以市售三大廠為主。中藥腎病變之可能機轉主要是與腎絲球過濾和腎小管分泌有關，因此當中藥傷害腎臟時最主要受到影響的地方便是腎絲球及腎小管。所以本篇研究採用近端腎小管細胞(LLC-PK1)與遠端腎小管細胞(MDCK) 來進行體外細胞模式及以SD大鼠為體內動物模式的篩選評估。 體外細胞模式以模擬人體每日服用複方濃縮中藥之最大劑量且完全吸收，並進行劑量效應探討，以50%及10%濃度稀釋複方濃縮中藥之最大劑量，最後以10%處理濃度進行細胞存活率實驗，若細胞存活率低於75%，則判定此複方濃縮中藥可能具有腎毒性複方濃縮中藥經口服吸收後，除考慮口服吸收率與會經血液稀釋外，尚會與血中蛋白質結合，也會經血液分佈到各組織器官，故接觸到腎臟細胞之濃度相對降低許多，而以稀釋至10% 的處理濃度進行細胞毒性之篩選。體外篩藥結果顯示，A廠小建中湯、桃仁承氣湯、小柴胡湯，B廠桑菊飲，C廠上中下通用痛風丸具細胞毒性傷害之風險。 體內動物模式以餵食SD大鼠A廠之複方濃縮中藥，連續14天，於犧牲前一天收集SD大鼠之血液與尿液，檢測美國食品藥物管理局(FDA)建議之七種生物標誌物(biomarkers)及血清肌酸酐(Creatinine)， 來評估複方中藥對腎之傷害，同時針對腎臟進行組織切片，進行病理分析。體內篩藥結果顯示，並不會造成大鼠腎臟之損傷。 另依據細胞實驗之結果，挑選幾種複方濃縮中藥，經人類腎小管細胞(HK2)之細胞存活試驗，其實驗結果之細胞存活率與近端腎小管細胞(LLCPK1)相似，未來近端腎小管細胞之試驗結果應可作為人類腎小管細胞之試驗結果之代表。 Abstract In recent years, Chinese herbal medicine induce renal damage caused growing attention. Most drugs were absorbed by glomerular filtration, proximal tubule secretion, distal tubule reabsorption and epithlial tubular cell degradation and other metabolic processes excreted. In this process, drugs are cumulatived nephrotoxicity and changed kidney of structure and function, therefore leading to kidney damage. Chinese herbal medicine has become a restriction of renal toxicity and the obstacle of clinical application. In order to ensure the safely use of traditional Chinese herbal medicine, it is necessary to strengthen Chinese herbal medicine of toxicology studies. However, the use of Chinese herbal medicine in Taiwan is common, so the herbs on the renal damage mechanisms of particular in-depth study. Study found that aristolochic acid(Aristolochia) caused renal damage, but it still contains other ingredients of Chinese herbal medicine caused renal toxicity, currently only a view of relevant literature and research. Therefore, the purpose of this study, the Chinese herbal medicine was selected because usually using in Taiwan, each Chinese herbal medicine was selected from three pharmaceutical companies. Chinese herbal medicine nephropathy mechanisms possibly associated with glomerular filtration and tubular secretion, and therefore damage the kidneys when the medicine most affected the glomerule and tubule. Therefore, this study using the proximal tubular cells (LLC-PK1) and distal tubule cells(MDCK) for in vitro cell models and in SD rats as animal models in vivo screening assessment. In vitro cell models to simulate the human daily maximum dose of Chinese herbal medicine and completely absorbed, and conduct dose dependent, 50% and 10% concentrations of diluted the maximum dose of medicine, and finally the 10% concentration for cell viability experiments, cell viability was below 75%, it is determined this Chinese herbal medicine potentially nephrotoxicity. Chinese herbal medicine orally absorbed, in addition to considering the orally absorption rate and hemodilution, but still with the blood protein binding, also the blood distributed to various tissues and organs, the renal cells exposed to relatively reduce the number density, so this study selected the 10% concentration of medicine to consider that if Chinese herbal medicine cause nephrotoxicity or not. The results showed that in vitro drug screening, Chinese herbal medicine probally caused nephrotoxicity containing Sheau Jiann Jong Tang, Tao Ren Cheng Chi Tang and Sheau Chair Hwu Tang in company A, Shang Ju Yin in company B, Shang Zhong Xia Tong Yong Tang Feng Wan in company C. In vivo animal models to SD rats fed Chinese herbal medicine of pharmaceutical company A for 14 days, the study collected the blood and urine of SD rats before sacrifice them. According Food and Drug Administration (FDA) proposed seven kinds of biomarkers ( biomarkers) and serum creatinine (Creatinine), to evaluate the Chinese herbal medicine for kidney damage, and for kidney biopsy performed for pathological analysis. The results showed that in vivo drug screening, the medicine did not cause damage to the kidney in rats. In addition, according to the results of in vitro experiments, the selection of several Chinese herbal medicine to cell survival test by human renal tubular cells (HK2), the results of cell viability is similar proximal tubular cells (LLCPK1). In the future, the cell survival test representative that proximal tubule cells(LLCPK1) should be used as the human renal tubular cells(HK2). |
| Original Identifier: | 101NDMC0551015 |
| نوع الوثيقة: | 學位論文 ; thesis |
| وصف الملف: | 163 |
| الإتاحة: | http://ndltd.ncl.edu.tw/handle/06998104477989907569Test |
| رقم الانضمام: | edsndl.TW.101NDMC0551015 |
| قاعدة البيانات: | Networked Digital Library of Theses & Dissertations |
| الوصف غير متاح. |