中国医科大学学报2025，Vol.54Issue(9)：814-820,7.DOI:10.12007/j.issn.0258-4646.2025.09.009
miR-202-5p通过靶向抑制ROCK1表达减轻急性呼吸窘迫综合征新生大鼠肺损伤
miR-202-5p alleviates lung injury in neonatal rats with acute respiratory distress syndrome by targeting the inhibition of ROCK1 expression
摘要
Abstract
Objective To explore the protective effect and mechanism of miR-202-5p on acute respiratory distress syndrome(ARDS)-induced lung injury in neonatal rats.Methods Sixty newborn SD rats were randomly divided into six groups:the control group(intraperi-toneal injection of normal saline by tail vein),ARDS group(ARDS model established via intraperitoneal injection of 4 mg/kg lipopolysac-charide by tail vein),ARDS+miR-NC group(ARDS rats receiving 2 mg/kg miR-NC via tail vein injection once every 4 h,with intervention for 12 h),ARDS+miR-202-5p group(ARDS rats receiving 2 mg/kg miR-202-5p via tail vein injection once every 4 h,with intervention for 12 h),ARDS+miR-202-5p+ov-NC group,and ARDS+miR-202-5p+ov-ROCK1 group(ARDS rats receiving 2 mg/kg miR-202-5p once every 4 h,with intervention for 12 h;with 6 × 108 plaque-forming units control or overexpression ROCK adenovirus administered via tail vein 3 days before lipopolysaccharide injection).Real-time quantitative PCR was employed to measure miR-202-5p and ROCK1 mRNA expression in rat lung tissue.Hematoxylin and eosin staining was performed to assess pathological lung injury.The lung tissue wet-to-dry weight ratio was determined to evaluate pulmonary edema.Western blotting was utilized to analyze ROCK1,Toll-like receptor 4(TLR4),phosphorylated-nuclear factor κB(p-NF-κB)p65,and phosphorylated-inhibitor of nuclear factor-κBα(p-IκBα)protein expression in lung tissue.The interaction between miR-202-5p and ROCK1 was validated using dual-luciferase reporter gene experiments.Results miR-202-5p expression was significantly down-regulated in ARDS rat lung tissue,while overexpression of miR-202-5p ameliorated pathological injury and pulmonary edema in ARDS rats.ROCK1 mRNA was upregulated in ARDS rat lung tissue;however,overexpression of miR-202-5p decreased the expression of ROCK1 in lung tissue of ARDS rats,while overexpression of ROCK1 reversed the protective effect of overexpression of miR-202-5p on lung injury in ARDS rats.Furthermore,miR-202-5p overexpression suppressed TLR4,p-NF-κB p65,and p-IκBα protein expression in ARDS rat lung tissue,an effect that was reversed by ROCK1 overexpression.Dual-luciferase reporter gene experiments confirmed that miR-202-5p directly targets ROCK1 mRNA 3'UTR.Conclusion miR-202-5p ameliorates ARDS-in-duced lung injury in neonatal rats through targeted suppression of ROCK1 expression,with the underlying mechanism potentially involving inhibition of ROCK1-mediated TLR4/NF-κB signaling pathway activation.关键词
急性呼吸窘迫综合征/miR-202-5p/ROCK1/TLR4/NF-κB信号通路/肺损伤Key words
acute respiratory distress syndrome/miR-202-5p/ROCK1/TLR4/NF-κB signaling pathway/lung injury分类
医药卫生引用本文复制引用
杨英阁,张晋雷,孙岩,陈升,梁正..miR-202-5p通过靶向抑制ROCK1表达减轻急性呼吸窘迫综合征新生大鼠肺损伤[J].中国医科大学学报,2025,54(9):814-820,7.基金项目
四川省医学(青年创新)科研课题(Q19025) （青年创新）
