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Study The Differential Expression Of MicroRNA In The Lung Tissue Of Mice With Acute Lung Injury (ALI)/acute Respiratory Distress Syndrome (ARDS) Induced By Mechanical Ventilation

Posted on:2018-04-03Degree:MasterType:Thesis
Country:ChinaCandidate:Q DongFull Text:PDF
GTID:2334330518477163Subject:Anesthesia
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Objective: Differentially expression and significance of microRNA in the lung tissue of mice with acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)induced by mechanical ventilation.Methods: Twenty C57 BL mice were divided into control group(10 mice)and ventilator-induced lung injury(VILI)group(10 mice)randomly.The rats in VILI group after endotracheal intubation were treated with 10 ml/kg tidal volume mechanical ventilation and muscle relaxant under anaesthetic,building(ALI/ARDS)model.The rats in control group were treated without muscle relaxant and mechanical ventilation but to spontaneous breathing.All mice were sacrificed 24 hours after operation,the left lung was excised to measure the wet-to-dry weight(W/D)ratio,and the right middle lobe was stained with hematoxylin and eosin(HE),the levels of BAL TNF-a?IL-1? were detected by ELISA.A microRNA mieroarray chip was used to profile miRNA expressions in the lung of rats in both groups.Predicted target genes among the different miRNAs an d analysised the pathway of the targets of miRNAs in this study.10 mice with ventilator induced lung injury as protection group,the most up-regulated miRNA antagonist and the most downregulated miRNA agonist were mixed in the same proportion,injected into the tail vein of mice as an intervention therapy.After 24 h,the mice were killed and the ratio of dry and wet weight,TNF-alpha,IL-1 beta factor were measured,and compared with the model group and the control group.Results: Compared with the control group,the VILI group mice had obvious respiratory symptoms,the pathology was characterized with ALI/ARDS,W/D ?lung injury score and TNF-a?IL-1? had significantly increased(P<0.01).The microarray chip results demonstrated that the expressions of 34 microRNAs were significantly changed in the ALI/ARDS mice.Among these miRNA 19 cases were up-regulated,15 cases were down-regulated.The target genes of these microRNAs might be involved in regnating the signal pathway of inflammation.The wet to dry weight ratio,TNF-alpha,beta IL-and lung injury score of the protection group was significantly lower than that in the model group,the difference was statistically significant(P < 0.017);The wet to dry weight ratio,TNF-alpha,beta IL-and lung injury score of protection group were higher than the control group,but no statistical significance(P > 0.05).Conclusion: Some miRNAs expressed differently in VILI group,Pathophysiology of VILI may be involved in the miRNA-regulated inflammation pathway et al.miRNA may play an important role in the occurrence and development of inflammatory reaction in lung injury.The antagonist of mi RNA-3473 and agonist of miR-98-5p may inhibit the inflammatory response of lung injury.
Keywords/Search Tags:microRNA, ventilator-induced lung injury(VILI), Acute lung injury, acute respiratory distress syndrome
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