解剖学杂志2023,Vol.46Issue(5):385-389,431,6.DOI:10.3969/j.issn.1001-1633.2023.05.004
miR-378通过抑制小鼠肝炎症反应改善非酒精性脂肪性肝炎的损伤
miR-378 ameliorates nonalcoholic steatohepatitis injury by inhibiting hepatic inflammatory response in mice
摘要
Abstract
Objective:To study the role and mechanism of miR-378 in the occurrence and development of non-alcoholic steatohepatitis(NASH)animal model.Methods:C57BL/6 mice were randomly divided into control(normal diet)group,NASH model(high fat diet)group,miR-378 inhibitor group(high fat diet + antagomir-378)group,negative inhibitor(high-fat diet + antagomir negative control)group.Liver coefficient and histopathological changes was observed in mice.The real-time quantitative PCR(qRT-PCR)was used to verify the expression of miR-378 in liver tissues of mice with NASH disease.The levels of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured by Olympus automatic chemical analyzer.The qRT-PCR was used to detect the expression levels of tumor necrosis factor-α(TNF-α),interleukin 4(IL-4),interleukin 6(IL-6),monocyte chemoattractant protein-1(MCP-1)and transforming growth factor-β(TGF-β)and collagen type l α2(Col1α2)in liver tissues.Results:Compared with the control group,the liver coefficients of NASH model group and negative inhibitor group were significantly increased.Compared with the NASH model group,the liver coefficient of miR-378 inhibitor group was decreased.The structure of hepatic lobule in the NASH model group was unclear,and there were obvious hepatocyte necrosis,hepatic cord disorder and inflammatory cell infiltration.Then in the miR-378 inhibitor group,the structure of the hepatic lobule was normal under light microscope,and the hepatocytes were neatly arranged,and the fat infitration was allevuated.The expression of miR-378 in the NASH model group and in the negative inhibitor group was significantly higher than that in the control group.Serum ALT and AST levels were significantly higher in NASH model group and in the negative inhibitor group than those in the control group.Compared with the NASH model group,miR-378 inhibitor group showed a significant decrease in the serum ALT and AST levels.The expression of TNF-α and IL-6 in the NASH model group and in the negative inhibitor group were significantly higher than those in the control group,while IL-4 was significantly decreased,and the difference in MCP-1 was not statistically significant.Compared with the NASH model group and in the negative inhibitor group,the expression of TNF-α and IL-6 in the miR-378 inhibitor group was decreased significantly and IL-4 was increased significantly.The expression of TGF-β and Col1α2 was significantly higher in the NASH model group and the negative inhibitor group than those in the control group.In comparison to the NASH model group,the miR-378 inhibitor group showed a significant decrease in the expression levels of TGF-β and Col1α2.Conclusion:MiR-378 may be a risk factor for NASH.Therefore,inhibiting the expression of miR-378 is beneficial for shortening the course and treatment of NASH disease,providing a new potential therapeutic target for NASH.关键词
非酒精性脂肪性肝炎/肝/微小RNA-378/炎症因子/小鼠Key words
non-alcoholic steatohepatitis/liver/microRNA-378/inflammatory factors/mouse引用本文复制引用
佘明豪,杨文辉,刘寒松,余洋,张磊..miR-378通过抑制小鼠肝炎症反应改善非酒精性脂肪性肝炎的损伤[J].解剖学杂志,2023,46(5):385-389,431,6.基金项目
河南省高等学校重点科研项目计划(20A320052) (20A320052)