枸杞多醣萃取物與甜菜鹼對大鼠肝臟星狀HSC-T6細胞活化 與纖維化之影響

Effects of Lycium barbarum polysaccharides extract and betaine on cell activation and liver fibrosis in rat hepatic stellate HSC-T6 cells

李柏盈(Bo-Ying Li)

指導教授 ： 趙振瑞

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2016年)

摘要

根據行政院衛生福利部公布之資料，2014年臺灣癌症前十大死因中，肝和肝內膽管癌排名高居第二，死亡百分比為17.7%，顯示肝臟疾病影響國人健康不容忽視。肝纖維化的成因與氧化壓力密切相關，其會促使肝臟星狀細胞活化與轉形生長因子(transforming growth factor-β, TGF-β)分泌，使膠原蛋白過度累積於細胞外基質，造成纖維化。枸杞多醣體(Lycium barbarum polysaccharides, LBP)在過去活體研究模式下顯示可藉抑制氧化壓力、發炎反應與細胞凋亡達到護肝的效果。本研究使用H2O2誘導細胞活化後，給予枸杞多醣萃取物，探討其對大鼠肝臟星狀HSC-T6細胞活化與纖維化指標之影響。結果顯示，細胞經5 μM H2O2誘導活化24小時後，α-平滑肌肌動蛋白(α-smooth muscle actin, α-SMA)、TGF-β1及基質金屬蛋白酶(matrix metalloproteinase, MMP)-2蛋白表現量較控制組顯著上升，10、50 μg/mL的LBP及betaine皆可以使α-SMA蛋白表現量顯著下降；50 μg/mL LBP與betaine可以使TGF-β1與matrix metalloproteinase (MMP)-2蛋白表現量顯著下降。10 μg/mL LBP可組織金屬蛋白酶抑制物(tissue inhibitor of metalloproteinase, TIMP)-1蛋白表現量顯著較控制組降低；10 μg/mL betaine可使TIMP-2蛋白表現量顯著較控制組及誘發組高。顯示LBP與枸杞活性成分之一的betaine可抑制細胞活化與纖維化指標，可能可以減緩肝纖維化的發生，對於TIMP-1與TIMP-2蛋白表現亦有潛在調控的可能。

關鍵字

枸杞多醣體 ； 肝臟星狀細胞 ； 肝纖維化

並列摘要

According to the statistical report by the Ministry of Health and Welfare, cancers of liver and intrahepatic bile ducts have become the second leading cause of cancer death in Taiwan during 2014, and its mortality was 17.7%. Therefore, the prevention and therapy of liver diseases become important research topics in Taiwan. Pathogenesis of liver fibrosis is much related to oxidative stress. The fibrogenesis is indicated by the activation of hepatic stellate cells (HSCs) and accompanied with enhanced secretion of transforming growth factor-β (TGF-β) and deposition of extracellular matrix (ECM). Lycium barbarum polysaccharides (LBP) have liver-protecting effects in in vivo models via suppression of oxidative stress, inflammatory response, and apoptosis. We determined the effects of LBP on cell activation and fibrotic markers after the activation of rat HSC-T6 cells via H2O2. Our data showed that H2O2 at 5 μM activated HSC-T6 cells by significantly increasing the expression of alpha-smooth muscle actin (α-SMA), TGF-β, and matrix metalloproteinase (MMP)-2, which were significantly reduced by LBP and betaine at 10 and/or 50 μg/mL (p<0.05). The expression of TIMP-1 was significantly inhibited by LBP at 10 μg/mL; however, the expression of TIMP-2 was promoted by betaine at 10 μg/mL. The results indicated that LBP and betaine, one of the active components in Lycium barbarum L., possibly attenuate liver fibrosis through reduction of HSC activation and expression of fibrotic markers under H2O2-induced oxidative stress.
Keywords: Lycium barbarum polysaccharides, hepatic stellate cells, liver fibrosis

並列關鍵字

Lycium barbarum polysaccharides ； hepatic stellate cells ； liver fibrosis

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