Objective Radiation-induced pulmonary fibrosis(RIPF)is a dynamic,complex and long-term process involving multiple chemokines and cytokines that lead to irreversible and severe lung tissue damage and even failure.Salid...Objective Radiation-induced pulmonary fibrosis(RIPF)is a dynamic,complex and long-term process involving multiple chemokines and cytokines that lead to irreversible and severe lung tissue damage and even failure.Salidroside,the main active component of Rhodiola rosea,exhibits distinct pharmacological actions including an anti-fibrotic effect.The purpose of this study is to investigate the therapeutic effect of salidroside(SAL)on RIPF via Nr1d2 regulation,which may affect inflammation response and epithelial mesenchymal transformation(EMT).Methods The key genes involved in RIPF development were identified by combining differentially expressed gene(DEG)analysis(mRNA microarray dataset GSE41789 downloaded from the Gene Expression Ombibus database,GEO)with Quantitative real time polymerase chain reaction(qRT-PCR)validation.Mouse type II lung epithelial cells(MLE-12)were divided into control group(control),radiation-exposure group(IR),group with postradiation exposure plus SAL treatment(AIR+SAL),and group with pre/post-radiation exposure plus SAL treatment(ABIR+SAL).The MLE-12 cells in the IR,AIR+SAL,and ABIR+SAL groups were irradiated with a single dose of 6 Gy X-rays,and the latter two groups were treated with SAL at three concentrations(5,10,and 20μg/mL)for 24 h.A total of 48 C57BL/6J mice were randomly allocated into control group(control),radiation-exposure group(IR),group with post-radiation exposure plus SAL treatment(AIR+SAL),and group with pre/post-radiation exposure plus SAL treatment(ABIR+SAL).The mice in the IR,AIR+SAL,and ABIR+SAL groups were irradiated with a single thorax dose of 17 Gy X-rays.At 24 h after irradiation,the mice in the AIR+SAL group were intraperitoneally injected with SAL(10,20,and 40 mg/kg)for 21 days.The mice in the ABIR+SAL group were intraperitoneally injected with SAL(10,20,and 40 mg/kg)for 10 days before thorax irradiation and for 11 days after thorax irradiation.Results The mice in the IR group incurred lung injuries including haemorrhage,oedema,inflammatory cell infiltration,increased release of proinflammatory cytokines,and pulmonary fibrosis.SAL treatment evidently alleviated radiationinduced inflammation and pulmonary fibrosis in the irradiated MLE-12 and mice.Moreover,SAL hindered the expression of Nr1d2,which influencedα-SMA and E-cadherin expression.Notably,pre-treatment with SAL in the irradiated mice exhibited a significant preventive effect on RIPF development.Conclusions Salidroside alleviated pulmonary fibrosis development through multiple mechanisms,including relieving inflammation response.Moreover,the downregulation of Nr1d2 might suppressα-SMA and promote E-cadherin,which affected EMT.展开更多
文摘Objective Radiation-induced pulmonary fibrosis(RIPF)is a dynamic,complex and long-term process involving multiple chemokines and cytokines that lead to irreversible and severe lung tissue damage and even failure.Salidroside,the main active component of Rhodiola rosea,exhibits distinct pharmacological actions including an anti-fibrotic effect.The purpose of this study is to investigate the therapeutic effect of salidroside(SAL)on RIPF via Nr1d2 regulation,which may affect inflammation response and epithelial mesenchymal transformation(EMT).Methods The key genes involved in RIPF development were identified by combining differentially expressed gene(DEG)analysis(mRNA microarray dataset GSE41789 downloaded from the Gene Expression Ombibus database,GEO)with Quantitative real time polymerase chain reaction(qRT-PCR)validation.Mouse type II lung epithelial cells(MLE-12)were divided into control group(control),radiation-exposure group(IR),group with postradiation exposure plus SAL treatment(AIR+SAL),and group with pre/post-radiation exposure plus SAL treatment(ABIR+SAL).The MLE-12 cells in the IR,AIR+SAL,and ABIR+SAL groups were irradiated with a single dose of 6 Gy X-rays,and the latter two groups were treated with SAL at three concentrations(5,10,and 20μg/mL)for 24 h.A total of 48 C57BL/6J mice were randomly allocated into control group(control),radiation-exposure group(IR),group with post-radiation exposure plus SAL treatment(AIR+SAL),and group with pre/post-radiation exposure plus SAL treatment(ABIR+SAL).The mice in the IR,AIR+SAL,and ABIR+SAL groups were irradiated with a single thorax dose of 17 Gy X-rays.At 24 h after irradiation,the mice in the AIR+SAL group were intraperitoneally injected with SAL(10,20,and 40 mg/kg)for 21 days.The mice in the ABIR+SAL group were intraperitoneally injected with SAL(10,20,and 40 mg/kg)for 10 days before thorax irradiation and for 11 days after thorax irradiation.Results The mice in the IR group incurred lung injuries including haemorrhage,oedema,inflammatory cell infiltration,increased release of proinflammatory cytokines,and pulmonary fibrosis.SAL treatment evidently alleviated radiationinduced inflammation and pulmonary fibrosis in the irradiated MLE-12 and mice.Moreover,SAL hindered the expression of Nr1d2,which influencedα-SMA and E-cadherin expression.Notably,pre-treatment with SAL in the irradiated mice exhibited a significant preventive effect on RIPF development.Conclusions Salidroside alleviated pulmonary fibrosis development through multiple mechanisms,including relieving inflammation response.Moreover,the downregulation of Nr1d2 might suppressα-SMA and promote E-cadherin,which affected EMT.
