葫芦茶苷对四氯化碳致肝纤维化模型小鼠的保护作用及机制研究-中国药房

葫芦茶苷对四氯化碳致肝纤维化模型小鼠的保护作用及机制研究

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篇名：	葫芦茶苷对四氯化碳致肝纤维化模型小鼠的保护作用及机制研究
TITLE：	Protective Effect and Mechanism of Tadehaginoside on Hepatic Fibrosis Model Mice Induced by Carbon Tetra- chloride
摘要：	目的：研究葫芦茶苷对四氯化碳（CCl4）致肝纤维化模型小鼠的保护作用，并探讨其可能机制。方法：将昆明种小鼠随机分为正常组、模型组、秋水仙碱组（阳性对照，0.2mg/kg）和葫芦茶苷低、中、高剂量组（3、6、12mg/kg），每组10只。除正常组小鼠腹腔注射橄榄油外，其余各组小鼠均腹腔注射10％CCl4橄榄油溶液（5mL/kg）以复制肝纤维化模型，每周2次，连续8周。自第3周起，各给药组小鼠灌胃相应药物，正常组和模型组小鼠均灌胃等体积2％羧甲基纤维素钠溶液，每日1次，连续6周。采用酶联免疫吸附测定法检测各组小鼠血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、透明质酸（HA）、白细胞介素6（IL-6）的含量；采用分光光度法、逆转录-聚合酶链反应法、Westernblotting法分别检测其肝组织中羟脯氨酸（Hyp）、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）的含量，Ⅰ型胶原（Col-Ⅰ）、金属蛋白酶组织抑制因子1（TIMP-1）、TIMP-2mRNA以及基质金属酶2（MMP-2）、转化生长因子β（1TGF-β1）蛋白的表达情况。结果：与正常组比较，模型组小鼠ALT、AST、HA、IL-6、MDA、Hyp含量，Col-Ⅰ、TIMP-1、TIMP-2mRNA以及MMP-2、TGF-β1蛋白的表达水平均显著升高，SOD、GSH-Px含量均显著降低（P＜0.01）。与模型组比较，各给药组小鼠ALT、AST、HA、IL-6、MDA、Hyp含量，Col-Ⅰ、TIMP-1、TIMP-2mRNA以及MMP-2、TGF-β1蛋白的表达水平均显著降低，SOD、GSH-Px含量均显著升高（P＜0.05或P＜0.01）。结论：葫芦茶苷对肝纤维化模型小鼠具有肝保护和肝纤维化抑制的作用，其机制可能与抑制脂质过氧化和胶原蛋白合成，下调Col-Ⅰ、TIMP-1、TIMP-2mRNA以及MMP-2、TGF-β1蛋白的表达等有关。
ABSTRACT：	OBJECTIVE：To study the protective effect of tadehaginoside（TA）on liver fibrosis model mice induced by carbon tetrachloride（CCl4），and to investigate its mechanism. METHODS ：Kunming mice were randomly divided into normal group ， model group ，colchicines group （positive control ，0.2 mg/kg），TA low-dose ，medium-dose and high-dose groups （3，6，12 mg/kg），with 10 mice in each group. Those groups were intraperitoneally injected with 10％ CCl4-olive oil solution （5 mL/kg）to induce liver fibrosis model twice a week ，for consecutive 8 weeks；except that ，the normal group was intraperitoneally injected with olive oil. From 3rd week ，the mice in each administration groups were given relevant medicine intragastrically ，normal group and model group were given constant volume 2％ sodium carboxymethylcellulose solution intragastrically ，once a day ，for consecutive 6 weeks. The contents of ALT ，AST，HA and IL- 6 in serum of mice were test ed by ELISA. The contents of Hyp ， SOD，MDA and GSH-Px in liver tissues were detected by spectrophotometry. mRNA expression of Col- Ⅰ，TIMP-1 and TIMP-2 in liver tissue was detected by RT-PCR. The protein expression of MMP- 2 and TGF-β1 in liver tissue was detected by Western blotting. RESULTS ： Compared with normal group，the contents of ALT，AST，HA，IL-6，MDA and Hyp，the mRNA expression of Col- Ⅰ，TIMP-1 and TIMP- 2，as well as the protein exp ression of MMP- 2 and TGF-β1 were increased significantly ，while the contents of SOD and GSH-Px were decreased significantly （P＜0.01）. Compared with model group，the contents of ALT ，AST，HA，IL-6，MDA and Hyp ，the mRNA expression of Col- Ⅰ，TIMP-1 and TIMP- 2，as well as the protein expression of MMP- 2 and TGF-β1were decreased significantly ，while the contents of SOD and GSH-Px were increased significantly（P＜0.05 or P＜0.01）. CONCLUSIONS ：TA has a significant protective effect on liver tissue and anti-fibrosis effects in liver fibrosis model mice ，the mechanism of which may be associated with inhibiting lipid peroxidation and collagen synthesis ， down-regulating the mRNA expression of Col- Ⅰ，TIMP-1 and TIMP- 2 as well as the protein expression of MMP- 2 and TGF-β1.
期刊：	2020年第31卷第02期
作者：	唐爱存，韦燕飞，刘喜华，王明刚，卢秋玉
AUTHORS：	TANG Aicun，WEI Yanfei ，LIU Xihua，WANG Minggang ，LU Qiuyu
关键字：	葫芦茶苷；四氯化碳；肝纤维化；脂质过氧化；胶原蛋白；基质金属酶；金属蛋白酶组织抑制因子；转化生长因子β1；小鼠
KEYWORDS：	Tadehaginoside；Carbon tetrachloride ；Hepatic fibrosis ；Lipid peroxidation ；Collagen；MMPs；TIMPs；TGF-β1；
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