非類固醇抗發炎藥、茶及番瀉葉對腎毒素血中濃度之影響及機轉

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 藥學院 > 藥學系暨碩博士班 > 博碩士論文 > Item 310903500/58007

請使用永久網址來引用或連結此文件: http://ir.cmu.edu.tw/ir/handle/310903500/58007

題名:	非類固醇抗發炎藥、茶及番瀉葉對腎毒素血中濃度之影響及機轉 Effects of nonsteroidal anti-inflammatory drugs, teas and Folium Sennae on the serum concentrations of uremic toxins and relevant mechanisms
作者:	彭禹璇;Yu-Hsuan Peng
貢獻者:	藥學系博士班
關鍵詞:	非類固醇抗發炎藥;茶;番瀉葉;腎毒素;有機陰離子轉運蛋白;多重抗藥性蛋白;乳癌耐藥蛋白;nonsteroidal anti-inflammatory drugs;teas;Folium Sennae;uremic toxins;indoxyl sulfate;p-cresyl sulfate;organic anion transporters;multidrug resistance-associated proteins;breast cancer resistance protein
日期:	2016-01-15
上傳時間:	2017-03-22 17:31:26 (UTC+8)
出版者:	中國醫藥大學
摘要:	慢性腎病為一世界性的健康問題。Indoxyl sulfate (IS)、p-cresyl sulfate (PCS) 為親蛋白腎毒素，無法藉血液透析移除，其血中濃度與腎臟病、心血管疾病之進展及死亡率呈高度正相關，它們在生理 pH 環境下為陰離子，其體內之轉運、排除與有機陰離子轉運蛋白相關如 organic anion transporter (OAT) 1、OAT3。非類固醇抗發炎藥 (NSAIDs)、茶、番瀉葉口服後，血循環中主要分子以陰離子形式存在，可能與 IS、PCS 競爭相同的轉運蛋白。本研究探討 NSAIDs、茶、番瀉葉對 IS、PCS 血中濃度之影響及機轉。首先利用大鼠靜脈注射 IS，評估待測物對 IS 排除之影響。其次，建立慢性腎衰竭大鼠模型，探討綠茶對病態大鼠內生性 IS、PCS 血中濃度及腎功能之影響。最後利用細胞模型探討有機陰離子轉運蛋白在機轉中扮演之角色。結果顯示，ketoprofen、diclofenac 使 IS 之清除率下降，且增加腎臟中的濃度，其機轉為抑制腎細胞上 OAT1、OAT3 對 IS 之攝入，並使 IS 從腎細胞之排出減少；綠茶使 IS 之清除率下降，並使慢性腎衰竭大鼠內生性 IS、PCS 之血中濃度增加，Cr、BUN 亦升高，其機轉為綠茶代謝物抑制腎細胞上 OAT1、OAT3 對 IS、PCS 之攝入。相反的，番瀉葉?珒ㄟ炊F IS 之清除率。綜言之，NSAIDs、綠茶透過抑制 OAT1、OAT3，使 IS 排除受阻。綠茶造成慢性腎病大鼠內生性的 IS、PCS 血中濃度增加，腎功能惡化。此實證資訊能提供醫療人員及慢性腎臟病人參考，希能減緩腎臟病及心血管併發症之惡化。 Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound and cannot be efficiently removed through hemodialysis. The elevated serum levels of IS and PCS were associated with the progression of CKD and cardiovascular diseases (CVD) as well as all-cause mortality. Because of the acidic properties, IS and PCS are existing as anions under physiological pH in the systemic circulation, and the transport and excretion of IS and PCS were mediated by organic anion transporters such as organic anion transporter (OAT) 1 and OAT3. Because the major molecules in the bloodstream after dosing non-steroidal anti-inflammatory drugs (NSAIDs), teas and Folium Sennae were anions, we hypothesized that they might compete with IS and PCS for the same transporters. Therefore, this study aimed to investigate the effects of NSAIDs, teas and Folium Sennae on the serum levels of IS and PCS. First, rats were injected an intravenous bolus of IS alone and with tested agents to evaluate the effects on the elimination of IS. Secondly, a chronic renal failure (CRF) rat model was established to investigate the effect of green tea (GT) on the serum levels of endogenous IS and PCS and the renal function. Furthermore, cell models were used to verify the involvement of individual transporters in the mechanism. The results showed that ketoprofen and diclofenac decreased the clearance of IS and increased its kidney concentration through inhibition on the uptake transport mediated by OAT1 and OAT3, as well as the apical efflux transporters. GT ingestion decreased the clearance of IS, and increased the serum levels of endogenous IS and PCS as well as Cr and BUN in CRF rats. Mechanism studies indicated that the serum metabolites of GT inhibited the uptake transport of IS and PCS mediated by OAT1 and OAT3. Conversely, Folium Sennae increased the systemic clearance of IS. In conclusion, NSAIDs and GT hampered the elimination of IS through inhibition on OAT1 and OAT3. GT increased the serum levels of endogenous IS and PCS, and deteriorated the kidney function of CRF rats. This information would be valuable for the clinical professionals and CKD patients to delay the progression of CKD and CVD.
顯示於類別:	[藥學系暨碩博士班] 博碩士論文

文件中的檔案:

檔案	描述	大小	格式	瀏覽次數
index.html		0Kb	HTML	27	檢視/開啟
index.html		0Kb	HTML	105	檢視/開啟

在CMUR中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....