2008-01-012024-05-15https://scholars.lib.ntu.edu.tw/handle/123456789/663305摘要：「以四氯化碳誘發大（小）白鼠慢性肝損傷實驗模式」為目前衛生署頒訂「健康食品之護肝功能評估方法」中唯一的動物模式，然四氯化碳屬毒物管制藥品，一般採購與使用受到規範限制，不易推廣。而早在1950年代即有以硫代乙醯胺(Thioacetamide, TAA)餵飼大鼠誘發肝纖維化損傷之報告，迄今此一模式仍常見諸文獻，且TAA在大（小）鼠所誘發肝纖維化損傷之病理變化類似人類的肝纖維化病變，因此，本計畫將嘗試利用TAA誘發大（小）鼠肝纖維化損傷，期能建立標準作業程序(standard operation procedure, SOP)，以作為「化學性肝纖維化損傷動物模式」的另一項選擇。計畫分三年進行，各年度之預期結果分述如下： 第一年：確定能誘發動物發生慢性肝纖維化損傷的TAA投藥劑量、方式、次數與時程，以及動物品種。另外，也評估以TAA誘發急性肝損傷模式的可能性。 第二年：比較同一物種而不同品系間對TAA誘發動物發生慢性肝纖維化損傷的反應差異，以供建立動物模式的品系選擇。同時也評估正對照組Silymarin的護肝劑量。 第三年：比較同一物種且同一品系中，性別對TAA誘發動物發生慢性肝纖維化損<br> Abstract: The sole official animal model to evaluate the hepatoprotective function of health foods is induced by CCl4. The fact that the sale and use of CCl4 have to be subjected to governmental control due to its high toxicity restricts the popularity of this animal model. The thioacetamide (TAA)-induced liver injury and fibrosis in murine had been first reported in 1950s. The histopathological features of hepatic fibrosis developed from TAA-treated rats and mice are similar to that observed in human patients of liver disease. Therefore, we plan to develop an alternative animal mode by TAA for evaluating the hepatoprotective function of health foods. In this 3-year project, the standard operation procedure for setting up the animal model of TAA-induced liver injury and fibrosis will be established. The expected results for each year are listed as the following: The first year: The dosage of TAA, as well as method, frequency and time course of TAA administration to induce chronic liver injury and fibrosis will be well confirmed. The animal species susceptible to TAA induction will be also verified. In addition, we will attempt to test the possibility for creating a TAA-induced animal model of acute liver injury. The second year: The differential expressions between distinct strains of rats or mice in response to TAA induction will be compared. In parallel, the dose of silymarin used as a positive control will be tested. The third year: The sexual effect on the development of TAA-induced liver injury and fibrosis in rats or mice will be examined. If any hepatoprotective drug is available, we will also test its potential as a positive control other than silymarin. All results from this project will be taken into consideration as essential criteria for establishing the TAA-induced animal model of chronic liver injury and fibrosis.硫代乙醯胺肝纖維化慢性肝損傷護肝功能thioacetamideliver fibrosischronic liver injuryhepatoprotective function