Hepatoprotection of silymarin against thioacetamide-induced chronic liver fibrosis
Hepatoprotection of silymarin against thioacetamide-induced chronic liver fibrosis
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DOI：
10.1002/jsfa.4723
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发表时间：
2012-05-01
影响因子：
4.1
通讯作者：
Chiu, Chih-Hsien
中科院分区：
文献类型：
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作者：
Chen, I-Shu;Chen, Yi-Chen;Chiu, Chih-Hsien
背景技术背景：肝纤维化是一种慢性肝损伤，通常由酒精、病毒或其他毒素引起，其特征是细胞外基质蛋白（如胶原蛋白）的过度积累。本研究旨在建立慢性肝损伤动物模型，探讨水飞蓟素保肝作用的分子机制。结果：硫代乙酰胺（TAA; 100 mg kg（-1）腹腔内（i.第页）每周注射3次）可有效诱导雄性ICR小鼠慢性肝纤维化。将24只ICR小鼠随机分为4组：（1）生理盐水组（i.第页）+ 水（管饲法）;（2）盐水（i.第页）+ 150 mg kg（-1）水飞蓟素（灌胃）;（3）100 mg kg（-1）TAA（i.第页）+ 水（灌胃）;（4）100 mg kg（-1）TAA（i.第页）+ 150 mg kg（-1）水飞蓟素（灌胃）。TAA治疗8周后，体重、血清胆固醇和甘油三酯降低，肝脏体积、ALT、AST和LDH值增加（P < 0.05）。水飞蓟素可减弱TAA的上述作用（P < 0.05），因此水飞蓟素也可减轻TAA引起的肝脏损伤。水飞蓟素对TAA诱导的慢性肝损伤的作用可能归因于肝MMP-2、MMP（-1）3、TIMP-1、TIMP-2、AP（-1）、KLF 6、TGF-β 1、α-SMA和COL-α 1的下调。结论：以TAA 100 mg kg（-1）每周3次腹腔注射成功建立了ICR小鼠慢性肝纤维化模型。同时，水飞蓟素对TAA诱导的肝损伤具有保护作用。(C)2011年化学工业协会
BACKGROUND: Liver fibrosis is chronic liver damage usually caused by alcohol, viruses or other toxins and is characterised by an excessive accumulation of extracellular matrix proteins such as collagen. The aim of this study was to establish an animal model of chronic liver damage and investigate molecular mechanisms of silymarin hepatoprotective effects. RESULTS: Thioacetamide (TAA; 100 mg kg(-1) intraperitoneal (i. p.) injection three timesweekly) effectively induced chronic liver fibrosis inmale ICRmice. Then 24 ICRmice were randomly divided into four groups: (1) saline (i. p.) + water (gavage); (2) saline (i. p.) + 150 mg kg(-1) silymarin (gavage); (3) 100 mg kg(-1) TAA (i. p.) + water (gavage); (4) 100 mg kg(-1) TAA (i. p.) + 150 mg kg(-1) silymarin (gavage). Eight weeks of TAA treatment resulted in lower body weight, serum cholesterol and triglycerides as well as increased liver size, ALT, AST and LDH values (P < 0.05). These TAA-induced effects were attenuated by silymarin (P < 0.05); therefore silymarin also ameliorated TAA-induced liver lesions. Effects of silymarin on TAA-induced chronic liver damage may be attributed to down-regulation of hepatic MMP-2, MMP(-1)3, TIMP-1, TIMP-2, AP(-1), KLF6, TGF-beta 1, a-SMA and COL-alpha 1. CONCLUSION: A mouse model of chronic liver fibrosis was successfully established by injecting 100 mg kg(-1) TAA three times weekly in male ICRmice. Meanwhile, silymarin showed hepatoprotection against TAA-induced damage. (C) 2011 Society of Chemical Industry