| Summary: | 碩士 === 國立陽明大學 === 解剖暨細胞生物學研究所 === 96 === In general, liver fibrosis can be regarded as a chronic wound healing process, characterized by increased deposition of connective tissue. Proliferation and activation of hepatic stellate cells (HSCs) are critical steps in the development of liver fibrosis. Previous studies have shown that excess oxidative stress causes activation of HSCs. During this process, transforming growth factor-b1 (TGF-b1) is known to be the most potent factor to induce HSCs activation and accumulation of exrtacellular matrix (ECM). Therefore, decrease of oxidative stress and suppression of growth or induction of apoptosis of HSCs are recognized as effective therapeutic targets for prevention of hepatic fibrosis. Caffeic acid phenethyl ester (CAPE), one of the major components of honeybee propolis, has been shown to have anti-oxidative, anti-hepatotoxic, anti-inflammatory and anti-tumor effects.
Our study is aimed to investigate the effect of CAPE against thioacetamide (TAA)-induced liver injury. We established a fibrotic C57BL/6 mouse model by TAA injections, and pretreated or co-treated with CAPE to test the anti-fibrotic effect of CAPE. Our data showed that (1) CAPE significantly abrogated hepatic fibrogenesis and reduced matrix density by immunostaining for type I collagen and Ki 67. (2) Mice treated with TAA and CAPE showed a significant reduction in aSMA、a1(I) procollagen mRNA expression. (3) RT-PCR results revealed CAPE could not down-regulate TGFb1 and TNFa mRNA expressions indicating the presence of CAPE could not reduce inflammatory reaction in liver after TAA-treatment. (4) CAPE pretreatment for one week and then combination with TAA/CAPE could attenuate hepatic fibrosis, but have associated with an intolerable high mortality rate. In conclusion, CAPE might be an effective therapeutic reagent for liver fibrosis, but be used cautiously.
|
|---|
