Exploration on the Molecular Mechanism of Qingdu Decoction in the Treatment of Acute-on-Chronic Liver Failure Based on the Effects of miR-34c in Mast Cell Exosomes on Intestinal Barrier Function
10.19879/j.cnki.1005-5304.202412662
- VernacularTitle:基于肥大细胞外泌体miR-34c对肠屏障功能的影响探讨清毒汤治疗慢加急性肝衰竭分子机制
- Author:
Jiaxuan YANG
1
;
Yue CHEN
1
;
Juan SHI
1
;
Lianyin GAO
1
Author Information
1. 首都医科大学中医药学院,北京 100069
- Publication Type:Journal Article
- Keywords:
acute-on-chronic liver failure;
Qingdu Decoction;
exosomes;
miR-34c;
intestinal epithelial cells;
tight junction protein
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2025;32(6):128-134
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effects of Qingdu Decoction on intestinal barrier function by regulating the miR-34c-mediated signaling pathway of human mast cells-derived exosomes;To explore its molecular mechanism in the treatment of acute-on-chronic liver failure(ACLF).Methods An inflammatory model was established by treating human mast cells with 1 μg/mL lipopolysaccharide.The mast cells were over-expressed with miR-34c using lentiviral transfection,and were divided into normal group,model group and miR-34c over-expression group.Exosomes were extracted from each group of mast cells.Human intestinal epithelial cells were divided into normal group,normal exosome group,model exosome group,miR-34c over-expression exosome group and Qingdu Decoction group(miR-34c overexpression exosomes+Qingdu Decoction),and corresponding treatment was given.The dual luciferase gene report confirmed the targeting relationship between miR-34c and myeloma associated oncogene zinc finger protein(MAZ).RT-qPCR was used to detect the expression of miR-34c in mast cells and intestinal epithelial cells,and Western blot was used to detect the expressions of MAZ,Occludin and ZO-1 protein.Results Compared with the normal group,the expression of miR-34c in mast cells treated with lipopolysaccharide and transfected with lentivirus significantly increased(P<0.01).The results of the dual luciferase reporter gene experiment showed that miR-34c could target and inhibit MAZ expression.The RT-qPCR results showed that compared with the normal group,the miR-34c expression in intestinal epithelial cells significantly increased in the model exosome group and miR-34c over-expression exosome group(P<0.05,P<0.01),while the miR-34c expression in Qingdu Decoction group significantly decreased compared with the miR-34c over-expression exosome group(P<0.01).The Western blot results showed that compared with the normal group,the expressions of MAZ,Occludin and ZO-1 proteins in the model exosome group and miR-34c over-expressing exosome group were significantly reduced(P<0.05,P<0.01),while the expressions of MAZ,Occludin and ZO-1 proteins in Qingdu Decoction group significantly increased compared with the miR-34c over-expressing exosome group(P<0.05).Conclusion The treatment of ACLF with Qingdu Decoction may be related to the regulation of the miR-34c-mediated signaling pathway in mast cell-derived exosomes and the up-regulation of intestinal epithelial tight junction protein expression.
