益肝消积方调控Ly6C^(hi)/Ly6C^(lo)巨噬细胞平衡干预早期肝硬化小鼠的实验研究  

Experimental study on the regulation of Ly6C^(hi)/Ly6C^(lo) macrophage balance by YiGan XiaoJi formula in early cirrhosis mice

作　　者：郑世豪 苟思媛 谢金池 糟小宾 齐文颖 王秋月 陈宇 司徒玮崧 叶永安[1,2] 张鹏 ZHENG Shi-hao;GOU Si-yuan;XIE Jin-chi;ZHANG Peng(Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing,100700,China.)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学肝病研究院 [3]北京中医药大学东方医院 [4]新加坡南洋理工大学生物科学学院

出　　处：《中西医结合肝病杂志》2025年第3期323-328,共6页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：国家自然科学基金资助项目(No.82104810)。

摘　　要：目的:研究益肝消积方(YGXJ)对早期肝硬化小鼠的疗效及其调控Ly6C^(hi)/Ly6C^(lo)巨噬细胞平衡的作用机制。方法:将C57BL/6小鼠分为空白组、模型组、中药干预组(YGXJ低、中、高剂量组),采用四氯化碳腹腔注射诱导小鼠早期肝硬化模型,造模9周。治疗组予中药YGXJ低、中、高三种剂量灌胃4周。采用HE染色、Masson染色观察各组小鼠肝组织病理染色情况,检测小鼠肝功能ALT、AST水平,Western-blot实验检测肝脏Ⅰ型胶原蛋白表达水平,免疫组织化学法检测肝脏F4/80、LY6C的表达,qRT-PCR检测肝脏内TNF-α、IL1-β、MMP9和MMP12的mRNA水平。结果:YGXJ干预4周后,对比模型组,YGXJ各剂量组小鼠肝脏炎性细胞浸润及胶原纤维沉积明显减少,肝硬化程度得到逆转,各剂量组肝功能ALT、AST水平有下降趋势,且均以YGXJ中剂量组疗效最为明显。YJXJ中剂量干预组肝脏CollagenⅠ表达较模型对照组有下降趋势。免疫组化显示YGXJ中剂量组F4/80和LY6C表达较模型组明显减少,且TNF-α、IL1-β的mRNA水平下降,MMP9、MMP12的mRNA水平升高。结论:YGXJ可改善小鼠的肝硬化程度及肝损伤情况,其作用机制可能与调控Ly6C^(hi)/Ly6C^(lo)巨噬细胞平衡有关。Objective:To study the efficacy of YGXJ on mice with early cirrhosis and its mechanism of action in regulating the balance of Ly6C^(hi)/Ly6C^(lo) macrophages.Methods:The C57BL/6 mice were divided into blank group,model group,and traditional Chinese medicine intervention group(YGXJ low,medium,and high dose group),and the early cirrhosis model was induced by intraperitoneal injection of carbon tetrachloride for nine weeks.The treatment group was given three doses of traditional Chinese medicine YGXJ low,medium,and high by gavage for four weeks.HE staining and Masson staining were used to observe the pathological staining of liver tissue in each group of mice,to detect the ALT and AST levels of mouse liver function,Western-blot assay to detect the expression level of liver type I collagen,immunohistochemistry to detect the expression of liver F4/80 and LY6C,and qRT-PCR to detect the levels of TNF-α,IL1-β,MMP9 and MMP12 mRNA levels in the liver.Results:After four weeks of YGXJ intervention,compared with the model group,the hepatic inflammatory cell infiltration and collagen fiber deposition in the YGXJ dose groups were significantly reduced.The degree of cirrhosis was reversed,and the hepatic function levels of ALT and AST in each dose group had a downward trend,and the therapeutic effect was most obvious in the medium-dose group of YGXJ.The expression of hepatic CollagenⅠin the medium-dose group of YGXJ had a downward trend compared with that of the model control group.The hepatic CollagenⅠexpression of YJXJ medium dose intervention group had a decreasing trend compared with the model control group.Immunohistochemistry showed that the expression of F4/80 and LY6C was significantly reduced in the YGXJ medium-dose group compared with that in the model group,and the mRNA levels of TNF-αand IL1-βwere decreased,and the mRNA levels of MMP9 and MMP12 were increased.Conclusion:The YGXJ improved the degree of cirrhosis and liver injury in mice,and its mechanism of action may be related to the regulation of Ly6C^(hi)/

关 键 词：益肝消积方 肝硬化 动物实验 巨噬细胞 

分 类 号：R575.2[医药卫生—消化系统]