The Expression Of JAK2/STAT1Signaling Pathway In Lung Tissue Of Rat ARDS And Intervention Role Of AG490and GCS

Objective:The purpose of this article is to investigate the expression of JAK2/STAT1signaling pathway and correlative cytokines in lung tissue of ARDS rats which are induced by oleic acid. And this article also discusses the changes of ARDS and JAK2/STAT1signaling pathway when ARDS rats were intervened by AG490and GCs, from which we can understand the effect of JAK2/STAT1signaling pathway in ARDS, and can explain the nosogenesis and the treatment mechanism for ARDS. At the same time, considering the macrophage’s important role in inflammation and ARDS, we examined the related genes’ expression in the macrophagic system RAW264.7which is induced by LPS and intervened by AG490and GCs simμltaneously, so we can analysis the effect of JAK2/STAT1signaling pathway in inflammation in vitro, and can provide some experimental foundation to explain the nosogenesis and the treatment mechanism for ARDS furthermore.Methods:Seventy-two healthy adult male SD rats were randomly divided into group Ⅰ (ARDS), group Ⅱ (ARDS+AG490), group Ⅲ (ARDS+GCs) and group Ⅳ (the control), each group was divided into2h,4h,8h three time points. Take blood from the abdominal aorta and detect blood gas, then observe the pathology in lung tissue throμgh HE dyeing,detect the expression of LIF in blood serum,TNF-a in lung tissue by ELISA method,and examine the expression of STAT1in lung tissue by RT-PCR,immunohistochemical and Western-blot.AW264.7macrophagic system stimμlated by LPS and divided into four groups: group (0.1μg/mlLPS),group (1μg/mlLPS),group (10μg/mlLPS),group (0.0mol/ml LPS),each group was divided into2h,6h,12h,24h,36h four time points. Detect the content of IL-6throμgh ELISA, finding appropriate concentration and time point, then intervene these cells by AG490and GCs, and detect the changes of STAT1’s mRNA by RT-PCR. Results:1. The ARDS rat model is certified by the resμlts of blood gas and pathology observation. The pathology observation indicated that the histopathological change situation in lung of group ARDS is the most serious, that of ARDS+AG490and ARDS+GCs is better, and that of the control group is normal entirely;2. The contents of LIF in serum and TNF-a in lung tissue in groups ARDS+AG490and ARDS+GCs are between that in the ARDS group and the control group;3. The expression of STAT1in group ARDS+AG490and ARDS+GCs is between that in ARDS group and control group;4. The content of IL-6in treated RAW264.7macrophages is higher than control group. During2h,6h and12h, the content of IL-6always at a high level and has a peak time at24h, but reduced significantly at36h;5. The expression of STAT1in RAW264.7macrophages in groups ARDS+AG490, GCs are between the ARDS group and the control group.Conclusion:1. JAK2/STAT1signaling pathway plays an important role in the process of ARDS and inflammation;2. AG490can inhibit the JAK2/STAT1signaling pathway, and then have anti-inflammatory effects;3. GCs can inhibit the JAK2/STAT1signaling pathway and have anti-inflammatory effects. But we can’t say that GCs resist inflammation throμgh inhibiting JAK2/STAT1signaling pathway.