| Objective:By establishing rat models with different concentrations of gap hypoxia,HE staining results of lung tissues of rats in each group were detected and analyzed,and microRNAs(miRNAs)in lung tissues were analyzed to screen out miRNAs with different expressions.Tumor Necrosis factor-a(TNF-α),interleukin-1β(interleukin-1β),interleukin-6(interleukin-6)in serum of rats were detected and analyzed.IL-6)expression level,and the correlation between the differentially expressed miRNAs and inflammatory cytokines TNF-α,IL-1β and IL-6 was analyzed.Methods:The rat models with different degrees of interstitial hypoxia were established.The episodes of interstitial hypoxia were controlled by oxygen chamber system for 12 weeks.The episodes were called IH-1 group with oxygen concentration of 5%.IH-2 group with oxygen concentration of 7.5%;IH-3 group with 10%oxygen concentration;The IH-4 group with oxygen concentration of 12.5%and the normal control group were the NC group.After 12 weeks of exposure,the rats were sacrificed and the serum and lung tissue samples were collected to detect the expression levels of miRNA,TNF-α,IL-1β and IL-6,and the differentially expressed miRNA of the rats with interstitial hypoxia were screened.The correlation between TNF-α,IL-1βand IL-6 was analyzed.Results:1.Twelve weeks after the establishment of the interstitial-hypoxic rat model,the lung tissues of each group were frozen slices to observe the cell morphology of each group.Macroscopic view:The lung tissue of normal control rats is pink,elastic and soft.There was no significant difference between IH-1 group and IH-2 group in naked eye.The color was slightly white and the volume was larger than that of normal control group.There was no significant difference between IH-3 group and IH-4 group by naked eye,which was dark red and slightly larger than the control group.The alveolar morphology of the NC group was intact,without obvious inflammatory cell infiltration and cell proliferation.In IH-4 group,the alveolar structure was relatively complete,a small amount of inflammatory cell infiltration was observed,and the lung interstitium was slightly thickened.In the IH-3 group,the inflammatory cell infiltration was increased,and the lung interstitium was significantly thickened,while in the IH-2 group,a large number of inflammatory cell infiltration was observed,the interstitium was significantly thickened,and the alveolar space became smaller.In IH-1 group,there were a large number of inflammatory cell infiltration around the blood vessels.The cells were pale and presented with fibroid changes.With the decrease of oxygen concentration,the infiltration of inflammatory cells in lung tissue increased and the lung interstitium thickened obviously.2.By miRNAs clustering analysis,compared with the NC group,the expression levels of miRNA-98-5p,miRNA-665-3p and let-7C-5p were decreased in the groups with different degrees of gap hypoxia,and with the increase of hypoxia degree,The down-regulation rates of miRNA-98-5p,miRNA-665-3p and let-7C-5p were increased.Compared with miRNA-665-3p and let-7C-5p,the expression level of miRNA-98-5p was the lowest in each group of interstitial hypoxia.3.Compared with NC group,the expression levels of TNF-α,IL-1β and IL-6 in different concentration gap hypoxia groups increased,and with the increase of hypoxia severity,the expression levels of TNF-α,IL-1β and IL-6 increased.4.There was a significant negative correlation between miRNA-98-5p and TNF-α,IL-1β and IL-6,with statistical significance(P=0.001).Conclusion:1.Compared with the NC group,inflammatory cell infiltration,alveolar stroma thickening and cell proliferation were observed in the lung tissues of the interstitial hypoxia rats with different concentrations.With the deepening of hypoxia,inflammatory cell infiltration increased,alveolar interstitium thickened obviously,and cell proliferation was obvious.2.The expression levels of let-7c-5p,miR-656-3p and miR-98-5p were decreased in the rat model of gap hypoxia with different concentrations,and decreased with the decrease of oxygen concentration,in which the down-regulation of miR-98-5p was most obvious.3.The expression levels of inflammatory cytokines TNF-α,IL-6 and IL-1βincreased in different concentrations of interstitial-hypoxic rat models,and increased with the decrease of oxygen concentration.4.There was a significant negative correlation between miR-98-5p and TNF-α,IL-6 and IL-1β. |
