Baicalin protects intestinal mucosal barrier and intervenes acute graft-versus-host disease by regulating autophagy / 中国组织工程研究

ABSTRACT

BACKGROUND: Acute graft-versus-host disease is one of the important complications of early death after hematopoietic stem cell transplantation. How to intervene in the course of graft-versus-host disease is a hot topic. OBJECTIVE: To explore the mechanism of baicalin regulating autophagy in the treatment of acute intestinal graft-versus-host disease. METHODS: Within 4 hours after 60Co irradiation in CB6F1 mice, mononuclear cell suspension (bone marrow + spleen) of Balb/c mice was immediately infused into the tail vein to establish haploid hematopoietic stem cell transplantation model. On the day after the establishment of the model, the rats in the model group were intragastrically given normal saline and the rats in the treatment group were intragastrically given baicalin at a dose of 30 mg/(kg·d) for 14 days. After treatment, clinical evaluation of acute graft-versus-host disease was conducted in mice. Pathological grade of acute graft-versus-host disease of small intestinal mucosa was analyzed. Autophagic vesicles in small intestinal mucosa were observed by transmission electron microscopy. Levels of reactive oxygen species in intestinal epithelial cells were detected by flow cytometry. The expression levels of autophagy related proteins LC3-II, LC3-I and Beclin1 were detected by western blot assay. RESULTS AND CONCLUSION: The scores of acute graft-versus-host disease and intestinal mucosa pathology grade in the treatment group were significantly better than those in the model group. Under transmission electron microscope, there were autophagic vesicles in the model group, but the mitochondrial structure was seriously damaged. In the treatment group, there were more autophagic vesicles and the mitochondrial structure was relatively intact. The level of reactive oxygen species in small intestinal epithelial cells in the treatment group was lower than that in the model group (P < 0.01). The expression level of LC3II/I and Beclin1 in the treatment group was significantly higher than that in the model group (P < 0.01). The results showed that baicalin could reduce the level of reactive oxygen species, increase the autophagy level of intestinal mucosal cells, protect intestinal mucosal barrier, and reduce the incidence rate of acute graft-versus-host disease after transplantation.