Feasibility Study Of Cell Infusion On Treatment Of Pulmonary Fibrosis Induced By Paraquat

Objective: By establish a model of pulmonary fibrosis induced by intraperitonealinjection of paraquat in mice, to investigate the effects of different lung tissue cellpopulations on paraquat-induced pulmonary fibrosis and to study the possiblemechanism of its effects.Methods:Ⅰ.to select the optimal paraquat dosage by a single intraperitoneal injectionof different concentrations of paraquat to establish a model of pulmonary fibrosis.1.Animal grouping:60healthy female C57BL/6mice were randomly divided into sixgroups according to the paraquat dosage:the saline control group,30mg/kg paraquatgroup,40mg/kg paraquat group,50mg/kg paraquat group,60mg/kg paraquat group and80mg/kg paraquat group. Each group had10mice;2. Model Preparation: the mice inmodel groups were injected intraperitoneal30mg/kg、40mg/kg、50mg/kg、60mg/kg and80mg/kg paraquat while the control group were administrated0.9%sodium chloridesolution;3.Observing indexes：mental status、life-span、body weight changes and thepathologic changes were observed,and the LD50was calculated, the sections afterHE staining were evaluated for the formation of pulmonary fibrosis by using Ashcroftscoring system.Ⅱ.to investigate the effects of different lung tissue cell populations onparaquat-induced pulmonary fibrosis.1. Animal grouping:90health female C57BL/6mice, were randomly divided into6groups,respectively,the normal control group,the50mg/kg paraquat group, the7AAD-infusion group,CD45-/CD31-/Sca-1-/EpCAM+infusion group,CD45-/CD31-/EpCAM-/Sca-1+cell infusion group;2.Model Preparationand flow sorting of lung tissue cell subsets: Each group were administrated a singleintraperitoneal injection of solution(50mg/kg),After24h, the mice in infusion groupwere administrated different lung tissue cell subsets respectively (FACS sorting) whilethe control group were administrated0.9%sodium chloride solution through tail vein;3.Observing indexes：mental status、life-span、body weight changes and the pathologicchanges were observed(HE/Masson staining),and the LD50was calculated, the sections after HE staining were evaluated for the formation of pulmonary fibrosis byusing Ashcroft scoring system.Results: Ⅰ. Modeling dose screening of paraquat-induced pulmonary fibrosis: TheLD50of intraperitoneal paraquat of28days was55.19mg/kg. All the paraquatgroup could induce some degrees of pulmonary fibrosis. The severity and earlymortality increased with the dosage. Ⅱ. Investigate the effects of different lung tissuecell populations on paraquat-induced pulmonary fibrosis: To the observation period of28days,there were different degrees of lung injury changes in the paraquat group andeach infusion groups compared with the control group, the difference was statisticallysignificant(p <0.05); the pathological changes of lung tissue were improved in each lungcell populations infusion groups compared with the paraquat group, the difference wasstatistically significant (p<0.05); there was no significant difference among infusiongroups.Conclusion: The more appropriate paraquat dosage is40mg/kg or50mg/kg,Resercherscan select modeling dose according to different purposes;infusion of different lungtissue cell populations can decrease paraquat-induced pulmonary fibrosis in mice, inparticular, the infusion of single lung cell subsets also play its repair effects,but theexact mechanism is yet to be confirmed by further studies.