Regulation of miR-17 on Acute Lung Injury in Mice through TLR4/MyD88/NF-κB Pathway
DING Xiaopei
WANG Shibo
YU Dawei
WANG Zhongxiang
CHEN Tao
ZHANG Ye
Abstract：Objective To investigate regulation mechanism of miR-17 on acute lung injury(ALI)in mice through Toll like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transcription factor kappa B(NF-κB)sig-naling pathway.Methods A total of 40 6-8 week male C57BL/6 mice were randomly divided into sham operation group,model group,over-expression group and low-expression group,with 10 mice in each.The sham operation group was treated with normal saline 1 mg/kg in the trachea,while the other 3 groups were treated with lipopolysaccharide 1 mg/kg in the trachea to establish ALI model.Model group,over-expression group and low-expression group were injected with miR-17 empty vector,over-expression and low-expression recombinant plasmids 1 mg/kg through tail vein,the sham operation group was injected with equal amount of normal saline 1 mg/kg,once daily for two consecutive weeks.After 2 weeks,hematoxylin-eosin(HE)staining was used to observe pathological changes in lungs,lung injury score was calculated.The arterial oxygen partial pressure,oxygenation index,wet-to-dry weight ratio of lung tissues,protein concentration in bron-choalveolar lavage fluid(BALF),tumour necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β)and IL-6 levels were compared.Reverse transcription polymerase chain reaction(RT-PCR)was used to detect miR-17 in lung tissues,Western blot was used to detect TLR4、MyD88、NF-κB protein expression in lung tissues.Results Compared with the sham operation group,the levels of TNF-α,IL-6 and IL-1β in BALF,lung injury scores,wet-to-dry weight ratio of lung tissues,protein concentration in BALF and protein ex-pression of miR-17,TLR4,MyD88 and NF-κB in lung tissues were elevated,while arterial blood oxygen partial pressure and oxygenation index decreased in the low-expression group,model group and over-expression group(P＜0.05);com-pared with the model group,the levels of TNF-α,IL-6 and IL-1β in BALF,lung injury scores,wet-to-dry weight ratio of lung tissues,protein concentration in BALF and protein expression of miR-17,TLR4,MyD88 and NF-κB in lung tissues were elevated,while arterial blood oxygen partial pressure and oxygenation index decreased in the over-expression group(P＜0.05);compared with the over-expression group,the levels of TNF-α,IL-6 and IL-1β in BALF,lung injury scores,wet-to-dry weight ratio of lung tissues,protein concentration in BALF and protein expression of miR-17,TLR4,MyD88 and NF-κB in lung tissues decreased,while arterial blood oxygen partial pressure and oxygenation index increased in the low-expression group(P＜0.05).Conclusion High expression of miR-17 may activate TLR4/MyD88/NF-κB signaling path-way to participate in the occurrence of ALI in mice.
Keywords：Acute lung injurymiR-17Toll like receptor 4Myeloid differentiation factor 88Nuclear transcrip-tion factor kappa B
Publication Date：2025-12-28
Online Publishing Date：2026-01-31(First online date of this platform, not the publication date of the document)
Pages：6( 1032-1037 )