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首页> 外文期刊>Journal of biomedical science. >Inhibitory effects of armepavine against hepatic fibrosis in rats
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Inhibitory effects of armepavine against hepatic fibrosis in rats

机译：阿姆六芬抗植物抗肝纤维化大鼠肝纤维化的抑制作用

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Activation of hepatic stellate cells (HSCs) plays a crucial role in liver fibrogenesis. armepavine (Arm,C_(19)H_(23)O_3N), an active compound from Nelumbo nucifera, has been shown to exertimmunosuppressive effects on T lymphocytes and on lupus nephritic mice. The aim of this studywas to investigate whether Arm could exert anti-hepatic fibrogenic effects in vitro and in vivo. A cellline of rat HSCs (HSC-T6) was stimulated with tumor necrosis factor-α (TNF-α) orlipopolysaccharide (LPS) to evaluate the inhibitory effects of Arm. An in vivo therapeutic study wasconducted in bile duct-ligated (BDL) rats. BDL rats were given Arm (3 or 10 mg/kg) by gavage twicedaily for 3 weeks starting from the onset of BDL. Liver sections were taken for fibrosis scoring,immuno-fluorescence staining and quantitative real-time mRNA measurements. In vitro, Arm (1-10μM) concentration-dependently attenuated TNF-α- and LPS-stimulated α-SMA protein expressionand AP-1 activation by HSC-T6 cells without adverse cytotoxicity. Arm also suppressed TNF-α-induced collagen collagen deposition, NFκB activation and MAPK (p38, ERK1/2, and JNK)phosphorylations. In vivo, Arm treatment significantly reduced plasma AST and ALT levels, hepaticα-SMA expression and collagen contents, and fibrosis scores of BDL rats as compared with vehicletreatment. Moreover, Arm attenuated the mRNA expression levels of col 1α2, TGF-β1, TIMP-1,ICAM-1, iNOS, and IL-6 genes, but up-regulated metallothionein genes. Our study results showed thatArm exerted both in vitro and in vivo antifibrotic effects in rats, possibly through anti-NF-κBactivation pathways.
机译：肝星状细胞（HSCs）的激活在肝纤维发生中起着至关重要的作用。 Armepavine（ARM，C_（19）H_（23）O_3N），来自Nelumbo Nucifera的活性化合物已显示出对T淋巴细胞和狼疮肾病小鼠的exertimmunosup抑制。该研究的目的是调查臂是否可以在体外和体内施加抗肝纤维原效果。用肿瘤坏死因子-α（TNF-α）或LPS）刺激大鼠HSCs（HSC-T6）的蜂窝线，以评估臂的抑制作用。体内治疗研究在胆管连接（BDL）大鼠中被导电。通过Gavage TwiceDaily给予BDL大鼠臂（3或10mg / kg），从BDL发作开始3周。肝脏切片被用于纤维化评分，免疫荧光染色和定量实时mRNA测量。在体外，臂（1-10μm）浓度依赖性地减弱TNF-α-和LPS刺激的α-SMA蛋白的表达和通过HSC-T6细胞活化而没有不良细胞毒性。臂也抑制TNF-α诱导的胶原胶原沉积，NFκB活化和MAPK（P38，ERK1 / 2和JNK）磷酸化。在体内，臂治疗显着降低了血浆AST和ALT水平，肝脏α-SMA表达和胶原含量，与车辆处理相比，BDL大鼠的纤维化分数。此外，臂衰减了COL1α2，TGF-β1，TIMP-1，ICAM-1，INOS和IL-6基因的mRNA表达水平，但是上调的金属硫蛋白基因。我们的研究结果表明，大鼠中，大鼠的体外和体内抗纤维化效应施加了亚马尔，可能通过抗NF-κBactivation途径。

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