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Anti-hepatofibrosis effect of Allium senescens in activated hepatic stellate cells and thioacetamide-induced fibrosis rat model

机译:大蒜对激活的肝星状细胞和硫代乙酰胺诱导的纤维化大鼠模型的抗肝纤维化作用

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摘要

>Context:Allium senescens Linn. (Liliaceae) (ASL) has been traditionally used in Korea and other Asian countries for improving digestive and liver functions.>Objective: The anti-hepatofibrosis effect of ASL ethanol extract in cellular and experimental fibrosis rat model was investigated.>Materials and methods:In vitro cell viability, cell cycle and apoptosis in hepatic stellate cells (HSCs) were studied using MTT assay, flow cytometry and Annexin V-FITC/PI staining. Thioacetamide (TAA; 200 mg/kg, i.p.)-induced liver fibrosis model using Sprague Dawley rats (n = 10) was developed in vivo by injecting TAA twice per week for 13 weeks. ASL (25 and 100 mg/kg) and silymarin (50 mg/kg) were administered through oral gavage 2 times per week from 7th to 13th week. Specific fibrotic-related biomarkers such as aspartate transaminase (AST), alanine transaminase (ALT), glutathione and hydroxyproline levels in serum were analyzed by spectrophotometer using commercial kits. Morphological, histopathological and fibrotic-related gene expression such as TGF-β, Col1α1 and α-SMA in liver tissues was estimated by hematoxylin and eosin staining, Picrosirius red stain and quantitative real-time polymerase chain reaction, respectively.>Results: ASL (0.1 mg/mL) and silymarin (0.05 mg/mL) treatment induced apoptosis (4.06% and 8.67%) in activated HSC-T6 cells, compared with control group (3.7%). The altered morphology in activated primary HSCs was also restored by ASL (0.1 mg/mL) treatment. Further, ASL (100 and 25 mg/kg) ameliorated the TAA-induced altered fibrotic-related biomarkers, histopathological changes and fibrotic-related gene expression significantly (p < 0.05 ∼ p < 0.001).>Conclusions: ASL can potentially be developed as a therapeutic agent in the treatment of hepatic fibrosis.
机译:>上下文:葱属林。 (Liliaceae)(ASL)在韩国和其他亚洲国家传统上用于改善消化系统和肝功能。>目的:研究了ASL乙醇提取物在细胞和实验性纤维化大鼠模型中的抗肝纤维化作用。>材料和方法:使用MTT分析,流式细胞仪和Annexin V-FITC / PI染色研究了肝星状细胞(HSC)的体外细胞活力,细胞周期和凋亡。通过体内注射硫胺乙酰胺(TAA;200μg/ kg,腹腔内),使用Sprague Dawley大鼠(n = 10)建立了肝纤维化模型,方法是每周注射两次TAA,共13周。从第7周到第13周,每周两次通过口管法给予ASL(25和100μmg/ kg)和水飞蓟素(50μmg/ kg)。使用商业试剂盒通过分光光度计分析血清中特定的纤维化相关生物标志物,例如天冬氨酸转氨酶(AST),丙氨酸转氨酶(ALT),谷胱甘肽和羟脯氨酸水平。通过苏木精和曙红染色,Picrosirius红染色和定量实时聚合酶链反应分别评估肝组织中的形态学,组织病理学和纤维化相关基因表达,例如TGF-β,Col1α1和α-SMA。>结果: ASL(0.1 mg / mL)和水飞蓟素(0.05 mg / mL)处理可诱导活化的HSC-T6细胞凋亡(4.06%和8.67%),而对照组(3.7%)。通过ASL(0.1μg/ mL)处理,还可以恢复活化的原发性HSC中形态的改变。此外,ASL(100和25μmg/ kg)明显改善了TAA诱导的纤维化相关生物标志物的改变,组织病理学变化和纤维化相关基因的表达(p <0.05〜p <0.001)。>结论: ASL可能被开发为治疗肝纤维化的治疗剂。

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