清化瘀毒方对CCl4肝纤维化模型大鼠PPARγ配体诱导信号介导途径的影响及与相关细胞因子的关系研究  

The correlation between PPAR ligand-induced signal mediated pathway and VEGF-A,bFGF and HIF-1a in CCl4 hepatic fibrosis model rats by Qinghua Yudu formula

作　　者：张斌 魏冬梅 王培劼 卞尧尧[2] 王邦才 何国浓 孙常波 毛飞寅 ZHANG Bin;WEI Dongmei;WANG Peijie;BIAN Yaoyao;WANG Bangcai;HE Guonong;SUN Changbo;MAO Feiyin(Ningbo Hospital of Traditional Chinese Medicine,Ningbo 315010,Zhejiang,China)

机构地区：[1]宁波市中医院,宁波315010 [2]南京中医药大学

出　　处：《现代实用医学》2024年第6期714-718,共5页Modern Practical Medicine

基　　金：宁波市科技计划项目(2019A610361);浙江省中医药科技计划(2022ZQ070);浙江中医药大学科研专项(2021FSYYZY06);宁波市医学科技计划(2021Y22)。

摘　　要：目的探讨清化瘀毒方对四氯化碳(CCl4)肝纤维化模型大鼠PPARγ配体(PPARγ)诱导信号介导途径的影响及与相关细胞因子的关系。方法将50只SD大鼠按照随机数字法分为空白组、模型组,清化瘀毒方高剂量干预组(高剂量组)、中剂量干预组(中剂量组)及低剂量干预组(低剂量组),每组各10只。模型组采用腹腔注射50%的CCl4橄榄油溶液建模,空白组大鼠采用腹腔注射等量0.9%氯化钠注射液。造模成功后空白组、模型组分别以等量0.9%氯化钠注射液灌胃,清化瘀毒方(每1 ml含生药0.1 g)低剂量组、中剂量组及高剂量组分别以50、100及200 mg·kg^(-1)·d^(-1)灌服,共计8周。比较5组肝组织病理学;免疫荧光法检测PPARγ、抗体Tolls样受体2(TLR2),免疫组化的方法检测血管内皮生长因子A(VEGF-A)、碱性成纤维细胞生长因子(bFGF)和低氧诱导因子-1α(HIF-1α)治疗干预后的表达;ELISA法检测细胞间黏附分子-1(ICAM-1)、血管内皮细胞黏附分子-1(VCAM-1)的相关表达。结果与空白组比较,各组TLR2、VEGF-A、bFGF、HIF-1α、ICAM-1和VCAM-1表达增强,清化瘀毒方低、中、高剂量干预组与模型组相比,明显减少。与空白组相比较,模型组PPARγ表达降低,清化瘀毒方治疗干预后,各组PPARγ表达增强。结论清化瘀毒方可以调控PPARγ、VEGF-A及HIF-1α,通过调节血管生成细胞因子的产生、迁移、黏附和收缩激活PPARγ及配体诱导信号,从而改善模型大鼠的肝损伤,血管生成和血管重构,达到抗肝纤维化作用。Objective Exploring the effect of Qinghua Yudu(QHYD)formula on the PPAR ligand(PPAR)in-duced signaling pathway in carbon tetrachloride induced liver fibrosis model rats and the relationship between related cytokines.Methods Fifty Sprague Dawley(SD)rats were randomly divided into the blank(normal)control group,model group,QHYD formula low-dose group,QHYD formula middle-dose group,QHYD formula high-dose group model(10 rats in each group).After successful modeling,the normal group was gavaged with an equal amount of saline.The low,medium,and high dose groups of QHYD formula were treated with 50,100,and 200 mg•kg^(-1)•d^(-1) by gavage for eight weeks,respectively.The liver histopathology was observed.Fluorescence expression of PPAR and TLR2 was detected by immunofluorescence assay.The expressions of vascular endothelial growth factor-A(VEGF-A),basic fibroblast growth factor(bFGF),and hypoxia inducible factor-1(HIF-1)were analyzed by im-munohistochemical methods.Meanwhile,the expressions of cytokines intercellular adhesion molecule-1(ICAM-1),vascular endothelial cell adhesion molecule-1(VCAM-1)were detected by ELISA.Results Compared with the blank group,the expressions of toll-like receptor 2(TLR2),VEGF-A,bFGF,HIF-1,ICAM-1,and VCAM-1 in each group was significantly increased.The PPAR expression was reduced in the model group when compared to the blank group.After intervention with the QHYD formula,the PPAR expression was enhanced.Conclusions QHYD formula can regulate PPAR,VEGF-A and HIF-1,and activate PPAR and ligand-induced signal by regulating the production,migration,ad-hesion and contraction of angiogenic cytokines,so as to improve the liver injury of model rats,angiogenesis and vascular remodeling to achieve the role of anti-liver fibrosis.

关 键 词：肝纤维化 过氧化物酶体增殖物活化受体 Toll样受体 细胞间黏附分子 血管细胞间黏附分子 

分 类 号：R392.5[医药卫生—免疫学]