红景天苷混悬液灌胃对小鼠急性放射性肺损伤的改善作用及其作用机制OACSTPCD

Objective To observe the improvement effect of intragastric administration of salidroside(SAL)suspen-sion on acute radiation-induced lung injury(RILI)in mice and to investigate its possible mechanism.Methods Forty-eight C57BL/6J male mice were randomly divided into the low-dose group,medium-dose group,high-dose group,dexa-methasone(DXM)group,model group,and control group,with 8 mice in each group.Except for the control group,mice in the other five groups were irradiated with 6 MV-X ray from a medical linear accelerator.On the second day after irradia-tion,the mice in the low-dose group,medium-dose group and high-dose group were given 15,30 and 60 mg/kg SAL sus-pension(once a day,for 7 days),and the mice in the DXM group were given 10 mg/kg DXM(once a day,for 7 days),mice in the normal control group and the model group were both given the same volume of normal saline(once a day,for 7 days).On the second day after the end of intragastric administration,peripheral venous blood of mice in each group was taken,and the lung tissues were taken after the mice were killed.The morphological changes of the lung tissues in each group were observed after HE staining.Serum inflammatory factors[interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)]were detected by ELISA.The mRNA levels of IL-1β,IL-6 and TNF-α in the lung tis-sues of mice were detected by real-time fluorescence quantitative PCR.Western blotting was used to detect nuclear factor-erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),glutathione peroxidase 4(GPX4)and transforming growth factor β(TGF-β)in the lung tissues of mice.Results The lung tissue injury of mice in low-,medium-and high-dose groups was improved to different degrees with the most significant improvement in the high-dose group.Compared with the high-dose group,the improvement of lung tissue injury in the mice of the DXM group was more obvious.Compared with the control group,the pulmonary alveolar septa in the model group were diffusely thickened and edematous,the alveolar cavity was obviously reduced or even disappeared,and the normal structure was obviously destroyed.Compared with the control group,the serum levels of IL-1β,IL-6 and TNF-α increased in the model group(all P<0.05).Compared with the model group,the serum levels of IL-1β,IL-6 and TNF-α decreased in the medium-and high-dose groups and DXM group(all P<0.05).Compared with the model group,the relative mRNA expression levels of IL-1β,IL-6 and TNF-α in the lung tissues of mice were lower in the medium-and high-dose groups and DXM groups(all P<0.05).Compared with the control group,the expression levels of Nrf2,HO-1 and GPX4 in the lung tissues of the model group increased,while the expression of TGF-β decreased(all P<0.05).Compared with the model group,the expression levels of Nrf2,HO-1 and GPX4 in the lung tissues increased,while the expression of TGF-β decreased in the medium-and high-dose groups and DXM group(all P<0.05).Conclusions Intragastric administration of SAL suspension can improve acute RILI in mice(60 mg/kg SAL suspension has the best effect).The mechanism of SAL suspension in improving acute RILI in mice may be that SAL promotes the expression of Nrf2 and HO-1 protein in the lung tissue and reduces oxidative stress and inflamma-tory reaction in mice.