miR-24-3p调节LIMK1/cofilin通路对急性呼吸窘迫综合征大鼠肺损伤的影响OA

Objective:To explore the effect of miR-24-3p modulating the LIMK1/cofilin pathway on lung injury in rats with acute respiratory distress syndrome(ARDS).Methods:The ARDS model was estab-lished by lipopolysaccharide(LPS)infusion.ARDS rats were randomly assigned to the ARDS group,miR-24-3p agomir(activator)group,and Agomir-NC group.Normal SD rats were taken as the control group.The lung function of rats was detected after intervention with miR-24-3p agomir and its negative control.The pathological examination of lung tissue was performed using HE and Masson staining.The relative expressions of miR-24-3p and LIMK1/cofilin pathway proteins in rat lung tissue were detected by qRT-PCR and Western blotting.ELISA was conducted to measure the levels of inflammatory factors in rat serum and bronchoalveolar lavage fluid(BALF).The total protein content in BALF,the number of neutrophils,and the activity of my-eloperoxidase(MPO)in lung tissue were determined.The effects of miR-24-3p on the migration and chemo-taxis of neutrophils induced by N-formylmethionyl-leaminyl-phenylalanine(fMLP)were quantitatively evalu-ated by using an automatic cell imaging system.Moreover,the dual-luciferase reporter gene assay was con-ducted to verify the targeted regulatory effect between miR-24-3p and LIMK1.Results:Compared with the control group,the lung compliance,PEF,arterial partial pressure of oxygen,and miR-24-3p expression in the ARDS group were significantly lower(P<0.05),while the ratio of collagen deposition area,the protein expressions of p-LIMK1 and p-cofilin,the ratios of p-LIMK1/LIMK1 and p-cofilin/cofilin,the levels of IL-2 and IL-6,the total protein content,the number of neutrophils,and the activity of MPO were significantly higher(P<0.05).Compared with the ARDS group,the lung compliance,PEF,arterial partial pressure of oxygen,and miR-24-3p expression in the miR-24-3p agomir group were significantly higher(P<0.05),while the ratio of collagen deposition area,the protein expressions of p-LIMK1,LIMK1 and p-cofilin,the ra-tios of p-LIMK1/LIMK1 and p-cofilin/cofilin,the levels of IL-2 and IL-6,the total protein content,the number of neutrophils,and the activity of MPO were significantly lower(P<0.05).MiR-24-3p agomir could reduce the migration rate and cumulative distance of neutrophils induced by fMLP.MiR-24-3p could target and regulate the expression of LIMK1.Conclusion:Upregulation of miR-24-3p can alleviate lung in-jury in ARDS rats,possibly by targeting and modulating the activation of the LIMK1/cofilin signaling path-way.