胶质细胞系源性神经营养因子/胶质细胞系源性神经营养因子受体信号通路在乳鼠先天性巨结肠相关性小肠结肠炎中的作用实验研究OACSTPCD

Objective:To investigate the role of glial cell line derived neurotrophic factor/glial cell line-derived neurotrophic factor receptor(GDNF/GFRα1)pathway in neonatal rats with Hirschsprung-associated enterocolitis(HAEC).Methods:The 21-day-old Ednrb knockout mice were HD model group(experimental group)and the same-day-old wild-type mice were control group,8 mice in each group.According to the morphology of colon tissue,the co-lon tissue of the experimental group was divided into narrow segment and dilated segment,and the colon tissue of the control group was divided into distal segment and proximal segment.The degree of intestinal inflammation was eval-uated by hematoxylin-eosin(HE)staining,and the levels of interleukin-10(IL-10)and tumor necrosis factor(TNF-α)were measured by Elisa staining GDNF/GFRα1 signaling pathway related genes(GDNF,GFRα1,tyrosine kinase re-ceptor[RET],nuclear transcription factor κB p65[NF-κB p65]and TNF-α)were detected by Western blot(WB).Results:HE staining showed that HAEC mainly occurred in the dilated segments of the colon.ELISA results showed that compared with the narrow segment of the intestines in the experimental group,the level of IL-10 in the dilated segment of the intestines was significantly decreased,and the level of TNF-α was significantly increased(both P＜0.05).The results of WB showed that compared with the narrow intestinal segment in the experimental group,the protein levels of GDNF,GFRα1 and RET in the dilated intestinal segment in the experimental group were significant-ly decreased,and the protein levels of NF-κB p65 and TNF-α were significantly increased(all P＜0.05).Conclusion:Inflammation in the dilated colon of HD mice is severe,which may be related to the inhibition of GDNF/GFRα1 sig-naling pathway and the abnormality of the intestinal neuroimmunoregulatory system.