Dexmedetomidine Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Regulation of microRNA-223-3p and HDAC4

Abstract

Objective: Acute lung injury (ALI) mainly causes acute respiratory distress syndrome, pneumonia, and acute respiratory failure. Due to the high lethality of ALI, this study was for the investigation of the mechanism by which dexmedetomidine (DEX) alleviated lipopolysaccharide (LPS)-induced ALI by regulating histone deacetylase 4 (HDAC4) and microRNA-223-3p (miR-223-3p). Methods: After LPS induction of ALI, the mice were treated with DEX (low, medium and high doses). Then the mice treated with LPS-induced ALI and high dose of DEX were transfected with miR-223-3p mimics or sh-HDAC4 to figure their roles in inflammation, and apoptosis in lung tissue of mice with ALI. Mouse monocyte RAW264.7 was treated with LPS-induced ALI and different doses of DEX and transfected with miR-223-3p mimics or sh-HDAC4 to explore their roles in proliferation, cycle distribution, inflammation, and apoptosis of RAW264.7 cells. RT-qPCR and western blot analysis were functioned to detect the expression of miR-223-3p, HDAC4, and TLR4/MyD88/NF-κB signaling pathway-related factors in lung tissue and RAW264.7 cells of mice with ALI. Results: Lowly expressed miR-223-3p and over-expressed HDAC4 were detected in lung tissue of mice with ALI and RAW264.7 cells. MiR-223-3p mimics or sh-HDAC4 decreased TLR4/MyD88/NF-κB signaling pathway-related factors in lung tissue of mice and RAW264.7 cells. MiR-223-3p mimics or sh-HDAC4 inhibited inflammation and cell apoptosis in lung tissue of mice with ALI, as well as facilitated proliferation, cycle entry and inhibited inflammation and apoptosis of RAW264.7 cells. Conclusion: This study suggests that DEX can alleviate LPS-induced ALI by mediating miR-223-3p and HDAC4 expression. This finding has key implications for developing the mechanism of ALI. Funding Statement: This work was supported by Science and Technology Department of Jilin Province (No. 20190701068GH). Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: This study was approved and supervised by the animal ethics committee of China-Japan Union Hospital of Jilin University. The treatment of animals in all experiments conforms to the ethical standards of experimental animals.