Effect and mechanism of human umbilical cord mesenchymal stem cells-derived exosome on radiation-induced lung injury in rats

YANG Zi-en; OUYANG Ming-yue; WANG Li-li; LIU Shuo; SUN Ling-yan; YAN Ying; LIU Yu; YU Hui-ying

doi:10.16048/j.issn.2095-5561.2024.04.05

Abstract：Objective To investigate the alleviating effect and mechanism of human umbilical cord mesenchymal stem cells-derived exosome(hUCMSC-Exo)on radiation induced lung injury(RILI)in rats.Methods The human umbilical cord mesenchymal stem cells(hUC-MSC)surface markers were detected by flow cytometry.The western blot,nanoparticle tracking analysis and transmission electron microscopy were used to identify hUCMSC-Exo.The 15 healthy SD rats were randomly divided into 3 groups:the control group,the irradiation group and the irradiation+Exo group,with 5 rats in each group.The rats in the irradiation+Exo group were injected with 100 μl hUCMSC-Exo once immediately after irradiation(the dose was 1×107 particles/μl),and the rats in the other 2 groups were injected with 100 μl normal saline and were killed 4 weeks after irradiation and samples were collected.The pathological changes of lung were observed by hematoxylin-eosin(HE)and Masson staining.The expression of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and interferon-γ(INF-γ)in serum of rats was detected by enzyme-linked immunosorbent assay(ELISA).The expressions of E-cadherin,Vimentin,transforming growth factor-β1(TGF-β1)and IL-1β in the right lung were detected by western blot.The mRNA expression of E-cadherin,Vimentin,IL-1β and IL-6 was detected by real-time fluorescence quantitative polymerase chain reaction(PCR).The expressions of E-cadherin,Vimentin,TGF-β1 and phosphorylation mothers against decapentaplegic homolog(p-Smad)in the right lung were detected by immunohistochemistry.Results Compared with the irradiation group,the inflammatory cell infiltration,collagen deposition and fibrous tissue hyperplasia were decreased in the lung tissue of the irradiation+Exo group(P＜0.05).Serum expressions of pro-inflammatory factors IL-1β,IL-6,TNF-α and INF-γ were decreased(P＜0.05).The expression of E-cadherin protein was increased,and the expression of Vimentin,TGF-β1,p-Smad and IL-1β protein was decreased(P＜0.05).The mRNA expression of E-cadherin was increased,while the mRNA expressions of Vimentin,IL-1β and IL-6 were decreased(P＜0.05).Conclusion hUCMSC-Exo can alleviate RILI by reducing the secretion of proinflammatory factors and inhibiting the progression of fibrosis.