Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (3): 587-594.doi: 10.13481/j.1671-587X.20210307

• Research in basic medicine • Previous Articles     Next Articles

Regulation effect of miR-146b on expression of intercellular adhesion molecule-1 in lung tissue of rats with acute respiratory distress syndrome

Guangwen LONG(),Qian ZHANG,Xiulin YANG,Chunling JI,Yukang DONG   

  1. Department of Emergency Internal Medicine,People’s Hospital,Guizhou Provincie,Guiyang 550002,China
  • Received:2020-10-04 Online:2021-05-28 Published:2021-05-28
  • Contact: Guangwen LONG E-mail:fxpx7833@163.com

Abstract: Objective

To observe the effect of miR-146b on the expression of intercellular adhesion molecule-1 (ICAM-1) in lung tissue of the rats with acute respiratory distress syndrome (ARDS), and to clarify the molecular mechanism of miR-146b in the treatment of ARDS.

Methods

The ARDS rat models were established by injecting oleic acid into the tail vein, and the successfully modeled rats were divided into model group(only given oleic acid), agomir negative control group and miR-146b agomir group, with 15 rats in each group; another 15 rats were selected as sham operation group(only given saline). One hour before operation, the rats in miR-146b agomir group were given miR-146b agonist for intervention, and the rats in agomir negative control group were given miR-146b agonist negative control reagent for intervention.Twenty-four hours after successful modeling, the partial pressure of oxygen (PaO2) and oxygenation index (OI) of the rats in various groups were detected by the blood gas system; the wet/dry weight ratios (W/D) of lung tissue of the rats in various groups were detected; the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) of the rats in various groups were detected by ELISA assay; the pathomorphology of lung tissue of the rats in various groups was observed by HE staining; the expression levels of miR-146b and ICAM-1 mRNA in lung tissue of the rats in various groups were detected by Real-time fluorescence quantitative PCR(RT-qPCR) method; the expression levels of ICAM-1 protein in lung tissue of the rats in various groups were detected by Western blotting method; the targeting relationship between miR-146b and ICAM-1 was detected by dual luciferase reporter system.

Results

Compared with model group and agomir negative control group, the PaO2 and OI, and the ratio of W/D of lung tissue of the rats in miR-146b agomir group were increased (P<0.01), and the levels of IL-1β, IL-6, and TNF-α in BALF of the rats in miR-146b agomir group were increased (P<0.01).The HE staining results showed that the structure of lung tissue of the rats in sham operation group was normal, there was no obvious inflammatory pathological changes, while the pathological changes such as alveolar hemorrhage, alveolar wall thickening and red blood cell exudation in the lung tissue were found in model group and agomir negative control group, and the above pathomorphological changes of lung tissue of the rats in miR-146b agomir group were alleviated. The expression levels of ICAM-1 mRNA and protein of the rats in miR-146b agomir group were significantly lower than those in model group and agomir negative control group (P<0.01), while the expression level of miR-146b was significantly higher than those in model group and agomir negative control group (P<0.01).The dual luciferase reporter system experiment results confirmed that the miR-146b could targetedly regulate the ICAM-1 gene.

Conclusion

MiR-146b can reduce the inflammation level of lung tissue of the ARDS rats, relieve the lung tissue function damage, and protect the lung tissue from ARDS by targeted down-regulation of the expression level of ICAM-1.

Key words: miR-146b, intercellular adhesion molecule 1, acute respiratory distress syndrome, targeted regulation, inflammatory factor

CLC Number: 

  • R56