台灣產生藥高氏柴胡對大白鼠肝纖維化之保肝
作用研究

柴胡(Bupleuri Radix)為『神農本草經』上品，係『傷寒論』少陽病的代表性藥物，自古即被作為保肝、解熱、解毒、消炎藥。〝高氏柴胡〞(Bupleurum kaoi Liu, Chau et Chuang)為台灣特有種植物，且其活性成分柴胡皂素（Saikosaponins）含量高於進口之北柴胡(Bupleurum chinense DC.) 及日本產之三島柴胡(Bupleurum falcatum L. var. komarowi Kitamura)，為優良的柴胡品種，為了進一步開發高氏柴胡的藥用及保健功能，本研究進行高氏柴胡對大白鼠肝纖維化之保肝作用機轉研究。實驗模式為對四週齡Sprague-Dawley(SD)品系大白鼠腹腔注射 Dimethylnitrosamine(DMN)10mg/kg，每週三次，連續注射四週以誘發肝纖維化，藥物治療組為市售進口北柴胡及台灣產高氏柴胡根部的水抽出物（water extract）、粗多醣體（crude polysaccharide）、粗皂素（crude saponin），在實驗最後二週經口投予，並以silymarin 作為藥物對照組。實驗結果顯示DMN 誘發肝纖維化組大白鼠的血清肝功能指數（sGOT、sGPT）和肝均質液中三酸甘油酯（Triglyceride）的數值皆明顯的上升（p<0.05~p<0.001）；而血清及肝均質液中總蛋白、白蛋白（Albumin）的數值則呈現明顯下降的趨勢（p<0.05~p<0.001）。另外，肝組織切片鏡檢亦顯示在DMN 誘發肝纖維化組中有顯著的發炎、纖維囤積(collagen accumulation)的現象，而纖維(collagen)的數值亦上升(p<0.05)。高氏柴胡和北柴胡根部的水抽出物、粗多醣體、粗皂素口服投予組則有意義地降低其sGOT、sGPT，顯示出改善肝損傷的能力。此外，尚有降低肝臟中三酸甘油酯的數值，維持肝的正常代謝功能，改善由DMN 所引起的肝臟傷害情況，並經由增加肝臟合成蛋白質的能力，使得肝臟中總蛋白及白蛋白的含量上升而具有改善肝實質細胞機能的作用。另外對於纖維囤積(collagen accumulation)的情況也因肝實質細胞機能的作用正常或其他可能之藥理活性途徑而有所改善，其纖維的數值亦下降。肝組織切片鏡檢亦顯示高氏柴胡和北柴胡之藥物治療組均具有明顯之肝修復及改善纖維囤積(collagen accumulation)的情況。且血清中之interferon-gamma 及interleukin-10 的表現量亦為高氏柴胡優於北柴胡。由以上實驗結果證實高氏柴胡和北柴胡對大白鼠肝纖維化均具有明顯的保肝、抗發炎、抗纖維化效果。高氏柴胡在增加血清中總蛋白質及白蛋白的含量及降低血清中 sGOT、sGPT 及肝臟中三酸甘油酯的能力方面，高氏柴胡比北柴胡具有更佳的保肝作用。

關鍵字

保肝；肝纖維化；高氏柴胡；生藥；免疫

並列摘要

Bupleurum kaoi Liu, Chau et Chuang, an endemic plant in Taiwan and one specie of Bupleuri Radix, is one of the most important traditional Chinese crude drugs for treating hepatitis and hepatoprotection. The three bioactive fractions-water extract (BKW), fraction of neutral polysaccharide (BKP) and saponin-enriched fraction (BKS) separated from B. kaoi, and the water extract (BCW), fraction of neutral polysaccharide (BCP) and saponin-enriched fraction (BCS) separated from B. chinense D.C. (as the reference plant) were examined effects against dimethylnitrosamine (DMN)-induced hepatic fibrosis in rats for 4 weeks. During last two weeks, rats in the liver injury model were daily administrated p.o. by the various doses of six fractions and silymarin as a reference compound. The liver anti-inflammation and fibrosis-improving effects of treatments were evaluated according to albumin, total protein and collagen in liver; L-asparate aminotransferase, triglyceride, albumin, total protein, interferon-γ (IFN-γ) and interleukin-10 (IL-10) in serum. Taken together, B. kaoi certainly exhibited potency of hepatoprotection and anti-inflammation, and the three fractions of B. kaoi further exhibited anti-hepatic fibrosis activities concerned with regulations of IFN-γ and IL-10.