大黄素对CCl4诱导小鼠肝纤维化的作用机制

摘要

Objective:To observe the therapeutic effect of emodin for CCl4-induced liver fibrosis and explore the pos-sible mechanism.Methods:24 male C57B6 mice were randomly divided into blank group,CCl4group and emodin group, and there were eight mice in each group.The Hepatic fibrosis was induced by intraperitoneal CCl4injection.The mice of emodin group received emodin via oral administration at a dosage of 40 mg·kg-·1d-1at the same time.Liver inflammation and fibrosis were observed by HE staining,Masson staining and α-Sma immunohistochemistry.CD45 +,CD11B+and F4/80 +cells in liver tissues were observed by immunohistochemistry.TGF-β1 mRNA expression were detected by real time PCR.Results:Mice of CCl4group and emodin group were injected with CCl4for 4 weeks.The pathological changes of liver cells and fibrosis were ob-served,which suggested that modeling succeeded.Compared with the CCl4group,the liver inflammation and hepatic fibrosis were significantly decreased.Intraperitoneal injection of CCl4increased the number of CD45 +,CD11B+and F4/80 +cells ex-pression in the liver tissue of mice.And emodin significantly reduced the number of these three types of cells,the correlation value was statistically significant.In addition,Compared to the blank group,the expression of TGF-β1 was significantly in-creased in CCl4group,while emodin reduced the CCl4-induced expression of TGF-β1,the correlation value was statistically significant.Conclusion:Emodin can reduce CCl4induced liver fibrosis,reduce liver fibrosis factor-TGF-β1 release,and its mechanism may be through the reduction of infiltration of monocytes-derived macrophages.%目的:观察大黄素对四氯化碳(carbon tetrachloride,CCl4)腹腔注射引起小鼠肝纤维化的作用及其机制.方法:雄性C57BL/6小鼠24只,按数字随机法随机分成空白组、模型组和大黄素组.每组8只.模型组和大黄素组通过腹腔注射CCl4制备小鼠肝纤维化模型,大黄素组并给予大黄素40 mg·kg-·1d-1悬液灌胃.HE染色观察小鼠肝脏的炎症和组织形态,Masson染色和a平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)免疫组化观察小鼠肝纤维化的程度,细胞膜表面分子CD45、CD11B和F4/80免疫组化观察小鼠肝组织中白细胞、单核细胞和巨噬细胞的数量,实时定量PCR检测了小鼠肝组织中转化生长因子-β1(Transforming growth factor-β1,TGF-β1)和单核细胞受趋化因子-1(monocyte chemoattractant protein-1,MCP-1)的表达.结果:模型组组小鼠注射CCl4四周后,光镜下观察到明显的肝细胞损伤和组织纤维化,提示肝纤维化模型建立成功.大黄素组小鼠肝组织炎症和肝纤维化程度较模型组明显减轻;CCl4腹腔注射引起小鼠肝组织中CD45 +、CD11B+、F4/80 +细胞浸润明显增加(P<0.01,P<0.01, P<0.01),而大黄素减少了CD45 +、CD11B+、F4/80 +细胞在肝纤维化期肝脏中的浸润(P<0.01,P<0.01,P<0.05);除此之外,与空白组比较,模型组中TGF-β1和MCP-1表达明显增加(P<0.01,P<0.01),而大黄素组TGF-β1和MCP-1显著降低(P<0.05,P<0.05).结论:大黄素可减轻CCl4引起的小鼠肝脏炎症和纤维化,其机制可能与通过减少单核巨噬细胞浸润、减少促纤维化因子TGF-β1的释放有关.