白藜芦醇抑制巨噬细胞中NF-κB通路发挥抗肝纤维化作用  

Resveratrol can improve liver fibrosis by inhibiting the NF-κB pathway in liver macrophages

作　　者：闫玉栋 姜海行[1] 罗薇[1] 胡榜利 于冰[3] 李凡 付艳君 YAN Yudong;JIANG Haixing;LUO Wei;HU Bangli;YU Bing;LI Fan;FU Yanjun(Department of Gastroenterology,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021;Department of Laboratory Research,Guangxi Medical University Affiliated Tumor Hospital;Department of Gastroenterology,the Second Affiliated Hospital of Guangxi Medical University;Department of Pharmacy,the Fourth People’s Hospital of Changsha,Hu’nan Province;The Affiliated Hospital of Guilin Medical University,China)

机构地区：[1]广西医科大学第一附属医院消化内科,广西南宁530021 [2]广西医科大学附属肿瘤医院实验研究部 [3]广西医科大学第二附属医院消化内科 [4]湖南省长沙市第四人民医院药剂科 [5]桂林医学院附属医院

出　　处：《胃肠病学和肝病学杂志》2020年第5期576-580,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家自然科学基金(81660107,81860116);广西自然科学基金(2018GXNSFAA281221)。

摘　　要：目的探讨白藜芦醇(Resveratrol)改善肝纤维化的机制是否通过抑制NF-κB通路来调节巨噬细胞活性实现。方法将实验小鼠随机分为3组,分别给予橄榄油、橄榄油+四氯化碳(CCl4)、橄榄油+CCl4+白藜芦醇腹腔注射,用Masson三重染色法评估肝纤维化严重程度,NF-κBmRNA及蛋白表达水平用RT-PCR和Westernblotting法测定;用RAW264.7巨噬细胞分别建立M0型、M1型和白藜芦醇干预的M1型巨噬细胞模型,再测定各组模型中NF-κBmRNA和蛋白表达水平。结果 Masson染色结果提示,白藜芦醇有改善小鼠肝纤维化的作用。RT-PCR和Westernblotting方法显示肝纤维化组织中NF-κBmRNA和蛋白表达水平升高,而白藜芦醇干预后表达水平下降。NF-κBmRNA和蛋白质的表达量在M1型巨噬细胞中较M0型明显升高,其表达水平在白藜芦醇干预M1型巨噬细胞模型后下降。结论 NF-κB通路活性在纤维化的肝组织及M1型巨噬细胞中明显增高,白藜芦醇可通过降低两者中NF-κB通路活性达到抗肝纤维化的作用。Objective To investigate whether Resveratrol plays the anti-fibrosis role by inhibiting the NF-κB pathway in macrophages.Methods The mice were randomly divided into 3 groups: normal control group, CCl2 group and intervention group and they were given intraperitoneal injection of olive oil, olive oil+carbon tetrachloride, olive oil+carbon tetrachloride+Resveratrol, respectively. The degree of liver fibrosis was detected by Masson staining, and the expression levels of NF-κB mRNA and protein were detected by RT-PCR and Western blotting. Lipopolysaccharide was used to induce the polarization of RAW264.7(M0 type macrophages) into M1-type cells, and after Resveratrol was administered, the expression levels of NF-κB mRNA and protein in the cells were detected.Results Masson staining showed that Resveratrol could significantly improve the degree of liver fibrosis in mice. RT-PCR and Western blotting showed that the expression levels of NF-κB mRNA and protein in the liver fibrosis tissues were increased, while they were decreased after the intervention of Resveratrol. After lipopolysaccharide induced M0 type macrophages to be M1 type, the expression levels of NF-κB mRNA and protein in the cells were increased, while they were decreased after the intervention of Resveratrol. Conclusion Liver fibrosis increases the activation level of NF-κB pathway in M1-type macrophage, and Resveratrol can play an anti-liver fibrosis effect by inhibiting NF-κB pathway activity in macrophages.

关 键 词：肝纤维化 巨噬细胞 白藜芦醇 NF-ΚB通路 

分 类 号：R575[医药卫生—消化系统]