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題名 | 中藥蓮子心在肝硬化鼠的療效研究=Therapeutic Study of a Chinese Herb Nelumbo Nucifera Semen on Cirrhotic Rats |
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作者姓名(中文) | 黃怡超; | 書刊名 | 中醫藥年報 |
卷期 | 28:6 2010.09[民99.09] |
頁次 | 頁265-284 |
分類號 | 414.5 |
關鍵詞 | 肝纖維化; 中藥; 蓮子心; 肝星狀細胞; Hepatic fibrosis; Chinese herb; Nelumbo nucifera semen; Armepavine; Hepatic stellate cells; |
語文 | 中文(Chinese) |
中文摘要 | 研究目的: 肝纖維化之特徵為肝臟星狀細胞(hepatic stellate cells)"活化",即星狀 細胞由靜態儲存維生素A細胞轉化為具有增生,收縮肝小竇,以及分泌細胞 外間質等特性而促進肝纖維化;如何逆轉成緩解肝纖維化是國際熱門研究課 題,目前並無"抗肝纖維化"之西藥,是以中藥之研發有其意義與契機,特 別針對是肝纖維化之分子形成機轉,包括:氧化壓力、肝星狀細胞增生與移 行、發炎反應等等。中藥蓮子心(Nelumbo nucifera semen)在"神農本草經" 記載味甘、澀、平;歸心、肝、胃經。現代研究顯示蓮子心萃取物具有抗氧 化壓力,清除活性氧化物,抑制紅斑性狼瘡腎炎(lupus nephritis)之效應。本 研究室初步結果顯示蓮子心萃取物在離體肝臟星狀細胞具有抑制纖維化之作 用,在開發治療抗肝纖維化之中藥生技研發上,有其意義。本計畫擬以(1)離 體細胞(包括肝臟星狀細胞),與(2)活體肝纖維化動物模式,建立各種生物 活性評估方法後,針對蓮子心萃取物及純化物armepavine,在離體及活體上 之抗肝纖維化及保護肝細胞之效應做研究,並進而探究其藥效機轉。 研究方法: 本計畫以(1)離體細胞(包括肝臟星狀細胞),與(2)活體肝纖維化動物模 式,評估蓮子心萃取之抗肝纖維化效應。肝星狀細胞經SV40病毒轉染之細胞株(HSC-T6),分別以TGF-β1與TNF-α引致其活化、分泌膠原蛋白,再以蓮子心萃取物(20 - 80 μg/ml)及純化物armepavine (1 - 10 μM)來評估其效應。活體動物效應研究以膽管結紮引致肝纖維化動物模式來評估其療效。以蓮子心萃取物(0.5 g/kg, bid)餵食三週後做療效評估—包括病理切片肝纖維化嚴重度、肝中膠原蛋白與α-SMA含量測定,血清生化肝功能指標(SGOT,SGPT)等等。 結果與討論: 由本研究結果顯示,蓮子心萃取物及純化物armepavine在離體肝臟星狀 細胞株上有抗肝纖維化效應,而活體動物療效評估顯示蓮子心萃取物有降低 肝纖維化鼠肝纖維化嚴重度與改善膽管結紮鼠血清生化肝功能指標(SGOT, SGPT)及鼠體重之效應。 |
英文摘要 | Aim: Many patients with chronic viral or alcoholic hepatitis are in the state of chronic liver injury and inflammation and may lead to cirrhosis, with replacement of normal parenchyma by fibrotic tissue. Fibrogenesis is a dynamic, complex, and progressive process and at some stages, it is reversible. No clinically efficacious anti-fibrotic drugs are yet available, and current research is directed to lessening or reversing fibrosis. The major culprit of liver fibrosis is activation of hepatic stellate cells (HSCs), characterized by transformation from a quiescent phenotype to a proliferative, contractile and secretory phenotype. Nelumbo nucifera semen(蓮子心)is a common medicinal plant used in Asia for the treatment of diarrhea, bleeding, fever, and infection. Extracts from Nelumbo nucifera semen have been shown to exert antioxidant, free radical scavenging activities with anti-inflammatory effects on lupus nephritic mice. In this study, we used: (1) in vitro cell assays (HSCs) and (2) an in vivo rat model of fibrosis to investigate the anti-fibrotic effects of Nelumbo nucifera semen extract and elucidate its mechanisms of action. Method: A cell line (HSC-T6) was challenged with cytokines or growth factors to induce HSC activation, and to evaluate inhibitory effects of Nelumbo nucifera semen extract and its active compound armepavine on activated HSCs. activated by TGF-β1 or TNF-α. A rat model of cirrhosis was induced by bile duct ligation for 3 weeks. Nelumbo nucifera semen extract (0.5 g/kg, bid) was administered continuously for 3 weeks. Assessment of therapeutic effects included: (A) histological scoring of liver fibrosis, (B) quantitation of hepatic collagens and α-smooth muscle actin (α-SMA), (C) serum biochemical markers including SGOT and SGPT, and (D) hepatic and body weights. Results and Conclusion: Both Nelumbo nucifera semen extract (20 - 80 μg/ml) and armepavine (1 - 10μM) concentration-dependently exerted inhibitory effects in terms of α-SMA protein expression and nuclear factor (NFκB) signaling on HSCs. activated by TGF-β1 or TNF-α. In the in vivo therapeutic study, Nelumbo nucifera semen extract treatment for 3 weeks significantly reduced hepatic fibrosis scores, collagen and α-SMA protein expressions and serum SGOT and SGPT activities, and body weight of BDL rats. Our results suggest that Nelumbo nucifera semen extract exerted inhibitory effects against hepatic fibrosis in rats. |
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