miR-34a与TNF-α在新生大鼠急性呼吸窘迫综合征肺损伤模型中的表达
Expression of miR-34a and TNF-α in neonatal rat model of acute respiratory distress syndrome lung injury
王秀 1张杰 1王晓丽 1霍梦月 1新春 1梅花1
作者信息
- 1. 内蒙古医科大学附属医院新生儿科,呼和浩特 010050
- 折叠
摘要
目的 探讨 microRNA-34a(miR-34a)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)在脂多糖(lipopolysaccharides,LPS)诱导的新生大鼠急性呼吸窘迫综合肺损伤模型中的表达意义及作用机制.方法 随机数字法将新生SD大鼠80只(7日龄)分为两组,两组均为40只,通过腹腔内注射4mg/kg LPS溶液建立不同时相分别为3、6、12、24 h的NARDS动物模型为实验组,腹腔内注射4 mL/kg等渗Nacl溶液建立健康参照组.测定肺湿/干重比值,观察肺组织病理学改变,实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)检测肺组织及细胞miR-34a表达,ELISA检测肺组织及TNF-α浓度.结果 实验组肺湿/干重值较对照组明显升高.苏木精-伊红(HE)染色显示实验组肺组织病变呈弥漫性改变,肺泡间隔增厚,部分出现肺泡融合,肺泡数目减少等.miR-34a、TNF-α表达水平在实验组的各个时间点较对照组升高,miR-34a表达与TNF-α呈正相关.结论 推测miR-34a通过正向调控TNF-α的表达,从而参与NARDS疾病的发生发展过程.
Abstract
Objective To investigate the expression of microRNA-34a(miR-34a)and tumor necrosis factor-α(TNF-α)in lung injury induced by lipopolysaccharides(LPS)in neonatal rats with acute respiratory distress syndrome(ARDS).The expression of mirna-34a and tumor necrosis factor-α(TNF-α)in lung injury induced by lipopolysaccharides(LPS)was determined by tumor necrosis factor.Methods A total of 807-day-old newborn SD rats were randomly(random number)divided into two groups,40 in each group,NARDS animal models were established by intraperitoneal injection of 4 mg/kg LPS solution for 3,6,12 and 24 hours respectively.Normal control group was established by intraperitoneal injection of 4 mL/kg isotonic Nacl solution.The wet/dry weight ratio of lung was measured to observe the changes of lung histopathology.The expression of miR-34a in lung tissues and cells was detected by quantitative real-time PCR(qrt-PCR).Results the wet/dry weight of lung in the experimental group was significantly higher than that in the control group.Hematoxylin-eosin(HE)staining showed diffuse changes in lung tissue,thickening of alveolar septum,partial alveolar fusion and decreased number of alveoli in experimental group.The expression levels of miR-34a and TNF-α in the experimental group were higher than those in the control group at each time point.Conclusions It is speculated that miR-34a can promote the release of more inflammatory factors by positively regulating the expression of TNF-α,thus affecting the occurrence and development of lung injury.The expression of miR-34a positively correlated with TNF-α.miR-34a may affect the regulation mechanism of lung injury by mediating the expression of TNF-α through some signal pathway or inflammatory reaction,it provides a new therapeutic target for the treatment of neonatal acute respiratory distress syndrome(NARDS).
关键词
miR-34a/肿瘤坏死因子-α/早产儿/新生儿/急性呼吸窘迫综合征Key words
Neonatal acute respiratory distress syndrome/miRNA-34a/TNF-α/Neonates引用本文复制引用
基金项目
内蒙古自治区自然科学基金(2020MS08034)
内蒙古自治区重点研发和成果转化计划(2022YFSH0088)
内蒙古自治区卫生健康委医疗卫生科技计划(202201291)
出版年
2024
NETL
NSTL
万方数据