Combination therapy with taurine, epigallocatechin gallate and genistein for protection against hepatic fibrosis induced by alcohol in rats.
Combination therapy with taurine, epigallocatechin gallate and genistein for protection against hepatic fibrosis induced by alcohol in rats.
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牛磺酸、表没食子儿茶素没食子酸酯和染料木黄酮的联合治疗可预防大鼠酒精诱导的肝纤维化。
DOI：
10.1248/bpb.b12-00548
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Lin, Xing
中科院分区：
文献类型：
--
作者：
Wei, Ling;Huang, Renbin;Zhang, Shijun;Lin, Xing
本研究旨在探讨牛磺酸、表没食子儿茶素没食子酸酯和金雀异黄素联合治疗在酒精诱导的大鼠肝纤维化模型中增强抗纤维化作用的可能性，并探讨其潜在机制。 24周内给大鼠灌胃不同量的酒精(5.0-9.5 g/kg)诱导肝纤维化。模型组仅给予酒精，治疗组分别给予相应药物加酒精，正常对照组给予等体积的生理盐水。联合治疗的抗纤维化效果通过肝组织学直接评估，并通过血清生化标志物、纤维化标志物和相关关键细胞因子/蛋白质的测量间接评估。结果表明，联合治疗可显着改善肝功能，表现为丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶、白细胞介素6和肿瘤坏死因子-α水平的降低。此外，联合治疗可有效抑制血清纤维化标志物和肝羟脯氨酸含量，抑制胶原沉积，减轻病理组织损伤。机制研究表明，联合治疗能够显着减少脂质过氧化，招募抗氧化防御系统，并抑制B细胞淋巴瘤2、α-平滑肌肌动蛋白、转化生长因子β(1)和小母抗十五麻痹同源物3蛋白的表达。我们的结果表明，联合治疗可有效减轻酒精诱导的大鼠模型中的肝损伤和纤维化。联合疗法提高的疗效及其良好的安全性可能代表一种新的肝纤维化保护方法。
This study was to investigate the possibility of enhancing the anti-fibrotic effect by using a combination therapy with taurine, epigallocatechin gallate and genistein in a rat liver fibrosis model induced by alcohol, and to explore its underlying mechanism. Hepatic fibrosis was induced by intragastric administration with various amount of alcohol (5.0-9.5 g/kg) within 24 weeks in rats. The model group received alcohol only, and treatment groups received the corresponding drugs plus alcohol respectively, while the normal control group received an equal volume of saline. The antifibrotic effects of combination therapy were assessed directly by hepatic histology, and indirectly by measurement of serum biochemical markers, the fibrosis markers and related key cytokines/proteins. The results showed that combination therapy could significantly improve the liver function, as indicated by decreasing levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyltransferase, interleukin-6 and tumor necrosis factor-α. Moreover, combination therapy could effectively suppress the serum levels of fibrosis markers and hepatic hydroxyproline content, inhibit collagen deposition and reduce the pathological tissue damage. Research on mechanism showed that combination therapy was able to markedly reduce lipid peroxidation and recruit the anti-oxidative defense system, and inhibit the expression of B-cell lymphoma 2, α-smooth muscle actin, transforming growth factor β(1) and small mothers against decapentaplegic homolog 3 proteins. Our results showed that combination therapy is effective in attenuating hepatic injury and fibrosis in the alcohol-induced rat model. The improved efficacy of the combination therapy with its good safety profile could represent a new protective approach for liver fibrosis.
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影响因子：
3.9
作者：
Mishra, Amartya;Paul, Sumit;Swarnakar, Snehasikta
通讯作者：
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影响因子：
3.9
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.2
作者：
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通讯作者：
Saab, S