Effect of miR-132 on lung injury in sepsis rats via regulating Sirt1 expression

H.-C. Zhu, W.-W. Song, M.-L. Zhao, R.-M. Zhang, X. Tian

Department of Critical Medicine, Zibo Central Hospital, Zibo, China. zhuhongchang1977@126.com

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• Infectious Diseases

OBJECTIVE: The aim of this study was to explore the effects of the expressions of micro ribonucleic acid (miR)-132 and sirtuin1 (Sirt1) on lung injury in sepsis rats, and to elucidate the regulatory relation between miR-132 and Sirt1.

MATERIALS AND METHODS: The model of sepsis-induced lung injury was successfully established in rats via injection of lipopolysaccharide (LPS) into the caudal vein (model group). Before modeling, the rats were infused with miR-132 antagomir via the trachea (miR-132 antagomir group) or intraperitoneally injected with the Sirt1 activator (SRT1720) (SRT1720 group). Meanwhile, the rats injected with an equal volume of normal saline via the caudal vein were enrolled in the control group. The expressions of the inflammatory factors interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were determined using enzyme-linked immunosorbent assay (ELISA). Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting were applied to detect gene and protein expressions in lung tissues, respectively. Targeted relationship between miR-132 and Sirt1 was explored using Luciferase reporter assay. In addition, tissue sections of the right lung were stained with hematoxylin-eosin (HE) to observe the degree of lung injury.

RESULTS: The model of sepsis-induced lung injury was successfully established in rats by LPS. The results showed that the expressions of IL-6, IL-1β, TNF-α and miR-132 rose significantly in lung tissues (p<0.01), whereas the expression of Sirt1 significantly declined (p<0.01). Lung injury was alleviated by miR-132 antagomir and SRT1720. Both miR-132 antagomir and SRT1720 significantly reduced the expressions of miR-132, IL-6, IL-1β and TNF-α (p<0.01). However, the expression of Sirt1 was remarkably upregulated in rats with lung injury (p<0.01). Luciferase reporter gene assay indicated that miR-132 regulated Sirt1 in a targeted manner.

CONCLUSIONS: MiR-132 may cause lung injury in sepsis rats by regulating the expression of Sirt1.

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