人脐带间充质干细胞改善放射性肺损伤远后效应的作用及机制研究OACHSSCD

Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cells(hUC-MSCs)on the long-term effects of radiation-induced lung injury(RILI)in mice induced by total body irradiation(TBI).Methods A total of 120 C57BL/6 mice were randomly divided into a control group(Ctrl group),an irradiation group(Rad group),and an irradiation+stem cell treatment group(Rad+MSCs group).Mice in the Rad group and the Rad+MSCs group received 6 Gy of 60 Co γ-ray TBI.Immediately after irradiation,the Rad+MSCs group was injected with an hUC-MSCs suspension(1×106/100 μL)via the tail vein.The homing of hUC-MSCs in the lungs was detected.The respiratory function,lung imaging,and pathological changes were evaluated at 4,12,and 20 weeks post-irradiation.The protein expressions of E-cadherin,Vimentin,α-SMA,and Egr1 in lung tissue were measured.Differentially expressed genes were screened and validated through transcriptomic analysis.Results The hUC-MSCs intervention significantly improved the 30-day survival rate post-irradiation.Respiratory function abnormalities were observed in the Rad group at 4 weeks post-irradiation,which progressively worsened over time and manifested as typical restrictive ventilatory dysfunction by 20 weeks.The hUC-MSCs intervention alleviated respiratory function impairment,with the most significant effect observed at 20 weeks.Pathological results showed that in the Rad group at 4 weeks post-irradiation,the lung tissue exhibited hyperemia and alveolar septal thickening;at 12 weeks,alveolar septal destruction was observed;and at 20 weeks,the tissue structure was loose with severe alveolar wall damage.The hUC-MSCs intervention ameliorated the pathological changes at all time points.At 20 weeks post-irradiation,the Rad group showed extensive ground-glass opacities,significantly increased collagen fiber deposition,downregulated E-cadherin expression,and upregulated Vimentin and α-SMA expression.Following hUC-MSCs intervention,these changes were mitigated,with epithelial markers rebounding and mesenchymal markers decreasing.Transcriptomic analysis identified 8 commonly differentially expressed genes,among which Egr1 expression exhibited dynamic changes:it was highly expressed in the Rad group at 4 weeks post-irradiation,but lowly expressed at 12 and 20 weeks.The hUC-MSCs intervention exerted a regulatory effect on Egr1 expression.Conclusion hUC-MSCs may improve the long-term effects of TBI-induced RILI by regulating the expression of Egr1 at different stages of RILI and by modulating the epithelial-mesenchymal transition process in the intermediate to late phases.