Screening of genes interacting with Sirt1 in inflammatory injury of acute respiratory distress syndrome in mice by gene chip

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Objective To Screen of Sirt1 interacting genes in acute respiratory distress syndrome in mice by gene chip, and to provide a reference for exploring the mechanism of action of Sirt1 in acute respiratory distress syndrome. Methods Sirt1 overexpression (Tg) mice and wild type (WT) mice were bought for research, and the genotypes of newborn mice were identified after reproduction. The Sirt1 expression differences in lung tissue of Tg mice and WT mice were test by Western Blot. Construction of ARDS mouse model, the expression of IL-6 in lung tissue of two ARDS mice was detected by ELISA, and pathological changes in lung tissue of ARDS mice by HE staining were observed. Screening of Sirt1 interacting genes in acute respiratory distress syndrome in mice by gene chip. Results Two different genotypes of Tg and WT were identified by polymerase chain reaction (PCR). The expression of Sirt1 in lung tissue of mice which detecting by Western blot suggested that the Sirt1 in lung tissue of Tg mice was significantly higher than that of WT mice (P=0.001). Pathological changes of lung tissue of mice after intraperitoneal injection of LPS after LPS via HE staining prompted that with the increase of LPS dosage, the injury degree of lung tissue of two kinds of mice increased obviously, and the degree of lung injury in WT-ARDS mice was more serious than that of Tg-ARDS mice, and when the dosage of LPS reached 20 mg/kg, the survival rate of the two groups was <50%. Two kind of mice were injected intraperitoneally with LPS (15 mg/kg), The expression of IL-6 in lung tissue gradually increased with the passage of time, The expression of IL-6 in lung tissue of 3 h, 6 h, 12 h, 24 h inWT-ARDS group was significantly higher than that in Tg-ARDS group(P<0.05), morever, the difference was the most significant especially in 12 h(P=0.007). Ubd, Ube2d2b, Olfm4, Il1rl1, Hivep3 and Lpar1 were identified as genes that interact with Sirt1 in mouse ARDS inflammatory lesions by gene chip screening. Conclusion Sirt1 may reduce the inflammatory damage in ARDS mice by regulating the expression of Ubd, Ube2d2b, Olfm4, Il1rl1, Hivep3 and Lpar1. Key words: Acute respiratory distress syndrome; Sirtuin type 1; Ubiquitin D; Nuclear factor kappa B