The Effects Of MicroRNA-155 Inhibitor In Lipopolysaccharide Induced Lung Injury By JAK/STAT1 Signaling Pathways

Objective To investigate the effects of microRNA-155(miR-155)inhibitor on endotoxemia induced lung injury by JAK/STAT1 signaling pathways.Methods One hundred and twenty BALB/c mice were randomly divided into control group(n=40),LPS group(n=40),and inhibitor+LPS group(n=40).LPS group and inhibitor+LPS group were injected 20 mg/kg of LPS by intra-peritoneal,while equivalent normal saline was given in control group.80 mg/kg miR-155 inhibitor for 3 days,twice per day was injected through the tail vein 24 h before LPS injection in inhibitor+LPS group.Mice were sacrificed at 6h,12 h,24h,48 h after LPS injection and lung tissue were collected.Levels of tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)of lung tissue were measured by enzyme-linked immunosorbent assay(ELISA).The injury of lung tissue was evaluated by histopathology.The expression of miR-155,STAT1 mRNA,SOCS1mRNA in lung tissue was assessed by fluorescent quantitation reverse transcription polymerase chain reaction(qRT-PCR).Results(1)miR-155 expression induced by LPS increased at 6h,12 h,24h and decreased at 48 h.miR-155 expression of LPS group was 6h(6.74±0.63),12h(11.04±0.99),24h(15.84±0.80)and 48h(4.03±2.55).The inhibitor+LPS group expressed less miR-155 compared with LPS group and the values showed significant differences at 12h(t=6.08,p<0.01),24h(t=23.64,p<0.01).(2)STAT1mRNA and SOCS1 mRNA both reached peak level at 6h post-LPS-injection.The level of STAT1 mRNA in LPS group was higher than that of inhibitor+LPS group and the values showed significant differences at 6h(t=4.41,p<0.01),12h(t=2.69,p<0.05),24h(t=3.62,p<0.01).The level of SOCS1 mRNA in inhibitor+LPS group was higher than that of LPS group and the values showed significant differences at 6h(t=4.55,p<0.01),12h(t=4.12,p<0.01),24h(t=2.38,p<0.05).(3)TNF-α reached its peak value at 6 hours and IL-10 reached its peak value at 48 hours.Both TNF-α and IL-10 expressed higher in LPS group than inhibitor+LPS group and all the values showed significant differences at 6h,12 h,24h(p < 0.01).(4)The results of pathologic examination indicated that the pneumonic injury of inhibitor+LPS group was milder than LPS group.Conclusion miR-155 increased in LPS induced acute lung injury and miR-155 inhibitor may suppress JAK/STAT1 signaling pathways and protect the lung tissue.