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通过 TGF-β1/Smads 通路改善硫代乙酰胺诱导的肝纤维化。

Ameliorates Thioacetamide-Induced Hepatic Fibrosis via TGF-β1/Smads Pathways.

机构信息

School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Suwon, 16419, Republic of Korea.

Department of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.

出版信息

Int J Biol Sci. 2019 Feb 13;15(4):800-811. doi: 10.7150/ijbs.30356. eCollection 2019.

DOI:10.7150/ijbs.30356
PMID:30906211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6429015/
Abstract

Hepatic fibrosis, characterized by persistent deposition of extracellular matrix (ECM) proteins, occurs in most types of chronic liver disease. The prevention of liver damage using extract of has been widely studied, but its molecular mechanism on the therapeutic efficacy of hepatic fibrosis is unclear. The aim of this study was to assess whether aquatic extract (DM) of ameliorates thioacetamide (TAA)-induced hepatic fibrosis. Hepatic fibrosis was induced by an intraperitoneal (i.p.) injection (150 mg/kg, twice per week) of TAA for 6 weeks. DM (50 mg/kg/day) or silymarin (50 mg/kg/day) was administered daily for 6 weeks. DM markedly reduced serum AST, ALT, ALP, and GTP in TAA-treated rats. DM significantly ameliorated the total glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity in TAA-treated rats. In particular, DM significantly reduced expression of α-SMA, type I collagen, vimentin, TGF-β1 and p-Smad2/3 in hepatic fibrosis rats. The protective effects of DM on progression of hepatic fibrosis were clearly shown by detecting 4-hydroxyproline concentration and histopathological examination in the liver. Therefore, our data suggest that DM dramatically prevented hepatic fibrosis by inhibiting oxidative stress and the TGF-β1/Smads signaling pathways.

摘要

肝纤维化是一种以细胞外基质（ECM）蛋白持续沉积为特征的疾病，发生在大多数类型的慢性肝病中。使用 的提取物预防肝损伤已被广泛研究，但它对肝纤维化治疗效果的分子机制尚不清楚。本研究旨在评估水提物（DM）是否能改善硫代乙酰胺（TAA）诱导的肝纤维化。通过腹腔内（i.p.）注射（150mg/kg，每周两次）TAA 6 周诱导肝纤维化。DM（50mg/kg/天）或水飞蓟素（50mg/kg/天）每天给药 6 周。DM 显著降低了 TAA 处理大鼠的血清 AST、ALT、ALP 和 GTP。DM 显著改善了 TAA 处理大鼠的总谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性。特别是，DM 显著降低了肝纤维化大鼠α-SMA、I 型胶原、波形蛋白、TGF-β1 和 p-Smad2/3 的表达。通过检测肝组织中 4-羟脯氨酸浓度和组织病理学检查，DM 对肝纤维化进展的保护作用得到了明显的证实。因此，我们的数据表明，DM 通过抑制氧化应激和 TGF-β1/Smads 信号通路显著预防肝纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e3/6429015/de85d5572837/ijbsv15p0800g008.jpg
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