高氏柴胡抗Diethylnitrosamine誘發大白鼠肝癌之肝臟保護體內活性研究

Preventive Effects of Bupleurum kaoi Against Diethylnitrosamine-induced Hepatocarcinogenesis in Rats

李欣樺(Hsin-Hua Lee)

指導教授 ： 顏銘宏

共同指導教授 ： 林俊清

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2006年)

摘要

高氏柴胡為台灣特有種之柴胡，其品質優於現今已知的各種柴胡，目前已知其對大白鼠具有明顯的保肝、抗肝纖維化、抗肝炎的效果。本研究目的為探討台灣產生藥高氏柴胡在化學誘導肝癌動物(大鼠)模式當中的預防作用。在體內試驗中，將Wistar大鼠以腹腔注射投與Diethylnitrosamine (DEN, 200mg/kg)在前兩週給予，接著在第三週~第六週口服給予2-Acetylaminofluorene (2-AAF, 20mg/kg)以誘發肝癌。藥物治療組為高氏柴胡根部的水抽出物（Water extract；BKW）、總多醣體（Polysaccharide-enriched fraction；BKP），以口服給予。實驗結果指出，高氏柴胡於化學誘發肝癌的癌前指標GST-P (Glutathione S-transferase, placental form)、細胞增生指標PCNA (Proliferating cell nuclear antigen)、及進階期的標記TGF-α (Transforming growth factor-alpha)皆有減少的效果，故在免疫組織染色學方面具有化學預防的效果，尤其是BKW。在血清生化值方面，BKW可降低Alkaline phosphatase (AKP)。抗氧化方面，投予BKW、BKP後，顯示兩者在肝均質液內SOD活性中皆會增加，肝臟脂質過氧化產物MDA的量則會降低，而且只有BKW可提升大鼠肝均質液內GSH的量。由上述的結果發現高氏柴胡具有預防由DEN所誘發的化學性肝癌，主要可能是藉由抗氧化作用並清除自由基所造成。

關鍵字

高氏柴胡 ； Diethylnitrosamine ； 肝癌 ； 抗氧化

並列摘要

Bupleurum kaoi Liu (Chao et Chuang) is an endemic plant to Taiwan, has been locally used as a hepatoprotective herbs for treating hepatitis, hepatic fibrosis. The preventive effects of water extract (BKW) and polysaccharide-enriched fraction (BKP) from B. kaoi against diethylnitrosamine-induced hepatocarcinogenesis in rats were evaluated in the present study. Male Wistar rats were received 2 doses of diethylnitrosamine (DEN, 200mg/kg, i.p.) 2 weeks apart. One week after the last injection of DEN, the rats were received 20 mg/kg body weight of 2-acetylaminofluorene (2-AAF) by gavage for 3 weeks. Hepatoprotective activity of BKW and BKP were observed in terms of reduced the number of putative preneoplastic altered foci hepatocytes which express with the marker placental form of glutathione-S-transferase (GST-P) and transforming growth factor-alpha (TGF-α). Furthermore, the proliferating cell nuclear antigen (PCNA) was reduced to show the inhibition of foci cell proliferation. In addition, treatment of BKW markedly reduced alkaline phosphatase (AKP) level in rats serum. In view of antioxidation, after treated with BKW and BKP, both of them were showed significantly increased the SOD level and decrease the lipid peroxidation level marker MDA in rats liver homogenates. In addition, only BKW increased GSH level in rats liver homogenates. Our findings suggested that B. kaoi (especially BKW) exhibited preventive activity on the progression phase during DEN-induced hepatocarcinogenesis in rats and the mechanism may due to handle oxidative stress.

並列關鍵字

Bupleurum kaoi ； Diethylnitrosamine ； Hepatocarcinogenesis ； Antioxidation

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