柔肝方上调肝组织Dectin-1及下调TLR4治疗CCl4造模小鼠肝纤维化的作用机制研究  

Mechanism of Rougan Decoction in treating CCl4-induced liver fibrosis mice by up-regulating Dectin-1 and down-regulating TLR4 in liver tissue

作　　者：黄凌鹰[1] 张鑫[1] 李曼[1] 陈博武 徐张迎 张雪 唐亦非[1] 高月求[1] 杨婉凤[1] HUANG Lingying;ZHANG Xin;LI Man;CHEN Bowu;XU Zhangying;ZHANG Xue;TANG Yifei;GAO Yueqiu;YANG Wanfeng(Department of Hepatology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai Key Clinical Laboratory of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院肝病科,上海市中医临床重点实验室,上海201203

出　　处：《上海中医药杂志》2020年第S01期167-170,176,共5页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81603589,81904117).

摘　　要：目的评价柔肝方对CCl4致肝纤维化小鼠的治疗作用及对Dectin-1、Toll样受体4(TLR4)表达的影响。方法C57BL小鼠60只,随机分为对照组、模型组和柔肝方组。模型组与柔肝方组均腹腔注射CCl4,每周3次,共6周;其中第3周起两组分别给予0.9%NaCl溶液与柔肝方灌胃,干预6周。检测各组小鼠肝功能,肝组织中Dectin-1、TLR4及相关下游蛋白和mRNA的水平,探讨柔肝方的抗肝纤维化作用。结果柔肝方组ALT、AST明显低于模型组,ALB明显高于模型组(P<0.01);柔肝方组肝脏假小叶形成和纤维化程度以及肝脏羟脯氨酸(Hyp)水平明显低于模型组(P<0.01);柔肝方组Dectin-1表达高于模型组(P<0.01),TLR4表达水平低于模型组(P<0.01);柔肝方组肌动蛋白α(α-SMA)、转化生长因子受体(TGF-β1 R)、血小板衍生生长因子受体(PDGFR)表达均明显低于模型组(P<0.01),且柔肝方组脊髓趋化因子受体2(CCR2)表达也明显低于模型组(P<0.01)。结论柔肝方具有较好的抗肝纤维化的作用,其机制可能与上调Dectin-1、下调TLR4的表达有关,也可能与下调CCR2表达有关。Objective To evaluate the therapeutic effects of Rougan Decoction on CCl4-induced liver fibrosis mice and its effects on the expressions of Dectin-1 and Toll like receptor 4(TLR4).Methods Sixty C57 BL mice were randomly divided into the control group,model group and Rougan Decoction group.The model group and the Rougan Decoction group were treated with CCl4 by intraperitoneal injection,3 times a week for 6 weeks.From the 3 rd week,the model group and Rougan Decoction group were treated with 0.9%NaCl solution and Rougan Decoction by intragastric administration,respectively,with a course of 6 weeks.The liver function,the protein and mRNA expression levels of Dectin-1,TLR4 and related downstream in liver tissue of mice in each group were detected to explore the anti fibrosis effect of Rougan Decoction.Results The levels of ALT and AST in the Rougan Decoction group were significantly lower than those in the model group,and the ALB level was significantly higher than that in the model group(P<0.01).The formation of pseudolobule,the degree of fibrosis and the level of hydroxyproline(Hyp)in the liver of the Rougan Decoction group were significantly lower than those of the model group(P<0.01).The expression of Dectin-1 in the Rougan Decoction group was significantly higher than that in the model group(P<0.01),while the expression of TLR4 was lower than that in the model group(P<0.01).The expressions of actin-α(α-SMA),transforming growth factorβ1 receptor(TGF-β1 R)and platelet-derived growth factor receptor(PDGFR)in the Rougan Decoction group were significantly lower than those in the model group(P<0.01),and the expression of chemokine receptor 2(CCR2)in the Rougan Decoction group was also significantly lower than that in the model group(P<0.01).Conclusion Rougan Decoction shows better anti fibrosis effect,which may be related to the up-regulation of Dectin-1 expression and down-regulation of TLR4 expression,or down-regulation of CCR2 expression.

关 键 词：柔肝方 DECTIN-1 TLR4 肝纤维化 

分 类 号：R285.5[医药卫生—中药学]