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并且其单体通过阻断TβR1-Smad2/3和TNF-α-NF-κB信号通路,在小鼠和LX2细胞中均能减轻肝纤维化。

and its monomers alleviate liver fibrosis both in mice and LX2 cells by blocking TβR1-Smad2/3 and TNF-α-NF-κB pathways.

作者信息

Wan Xing, Huang Han-Cheng, Wang Xiang-Peng, Hu Ze-Hua, Liu Ke-Yun, Huang De-Bin

机构信息

Medical College, Hubei University for Nationalities Enshi, Hubei, China.

Department of Emergency Medicine, The Central People's Hospital of Yichang Yichang, Hubei, China.

出版信息

Am J Transl Res. 2019 Jan 15;11(1):106-119. eCollection 2019.

Abstract

This study aimed to investigate the protective effects, effective constituents and preliminary mechanisms of on liver fibrosis and screen new high-efficacy drug for fibrosis. 112 male C57BL/6 mice were randomly divided into 14 groups: control group (CG), CCL group (CTG), low/medium/high dose of ethanol extracts (EAE), catechin (CA), dihydroquercetin (DHQ) and kaempferol (KA) groups. The study lasted for 30 days by injecting CCL in peritoneal cavity to make fibrosis model, all mice were sacrificed to observe morphological changes and collagenous fiber by HE and Masson staining, to test liver index, ALT, AST, to measure the expression of α-SMA and collagen I by immunohistochemistry and western blotting, to discuss the pathways of TβR1-Smad2/3 and TNF-α-NF-κB by WB and Elisa; after being evaluated the efficacy, anti-fibrosis drug of highest efficacy was chosen to repeat these indexes in human hepatic stellate cells-LX2. Results showed that EAE/CA/DHQ/KA prevented increases in liver index, ALT, AST, α-SMA, collagen I, TβR1, Smad2/3, TNF-α and p-NF-κB caused by CCL in dose-dependence, they also improved the liver morphology, decreased inflammatory cell infiltration and collagenous fiber in dose-dependence, CA' efficacy was best in mice; in LX-2, CA also decreased the expression of α-SMA, collagen I, TGF-β, Smad2/3. All findings suggested that could alleviate liver inflammation and fibrosis by inhibiting TβR1-Smad2/3 and TNF-α-NF-κB pathways, flavonoid were effective constituents and catechin was screened as a new star for its best performance.

摘要

本研究旨在探讨[具体药物名称未给出]对肝纤维化的保护作用、有效成分及初步机制,并筛选新的高效抗纤维化药物。将112只雄性C57BL/6小鼠随机分为14组:对照组(CG)、CCl4组(CTG)、低/中/高剂量[具体药物名称未给出]乙醇提取物(EAE)、儿茶素(CA)、二氢槲皮素(DHQ)和山奈酚(KA)组。通过腹腔注射CCl4建立纤维化模型,研究持续30天,处死所有小鼠,通过HE和Masson染色观察形态变化和胶原纤维,检测肝指数、ALT、AST,通过免疫组化和western blotting检测α-SMA和I型胶原的表达,通过WB和Elisa探讨TβR1-Smad2/3和TNF-α-NF-κB信号通路;评估疗效后,选择疗效最高的抗纤维化药物在人肝星状细胞-LX2中重复这些指标。结果表明,EAE/CA/DHQ/KA可剂量依赖性地阻止CCl4引起的肝指数、ALT、AST、α-SMA、I型胶原、TβR1、Smad2/3、TNF-α和p-NF-κB升高,还可剂量依赖性地改善肝脏形态,减少炎症细胞浸润和胶原纤维,CA在小鼠中的疗效最佳;在LX-2中,CA也降低了α-SMA、I型胶原、TGF-β、Smad2/3的表达。所有结果表明,[具体药物名称未给出]可通过抑制TβR1-Smad2/3和TNF-α-NF-κB信号通路减轻肝脏炎症和纤维化,黄酮类化合物是有效成分,儿茶素因其最佳表现被筛选为一颗新星。

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