Screening of mRNA expression differences of PI3K/Akt/eNOS in the aortic tissue of rats exposed to sodium fluoride based on mRNA sequencing / 中华地方病学杂志

ABSTRACT

Objective:To explore the effect of fluoride exposure on the gene expression of phosphatidylinositol-3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) in rat aortic tissue, and to provide a theoretical basis for studying the mechanism of cardiovascular injury caused by endemic fluorosis.Methods:A total of 40 male Wistar rats were divided into 4 groups (10 rats in each group) via the random number table method according to body weight (80 - 100 g), namely control group (drinking distilled water), low-dose, medium-dose and high-dose groups [drinking distilled water containing 50, 100 and 150 mg/L sodium fluoride (NaF), respectively]. The rats were free to drink and eat. After feeding for 90 days, rats were sacrificed and the aortic tissue was taken. Three aortic tissue samples from the control group and the high-dose group were taken for mRNA sequencing, the differential genes were screened, and the differential genes were analyzed by GO function enrichment analysis and KEGG function enrichment analysis. At the same time, the mRNA expression levels of PI3K, Akt and eNOS in the aortic tissue of rats in each group were determined by real-time fluorescence quantitative PCR.Results:Compared with control group, there were 756 differential genes in high-dose group, including 654 up-regulated genes and 102 down-regulated genes. These differential genes were mainly related to biological processes such as muscle contraction, muscle regulation, muscle tissue development, striated muscle cell development, muscle cell differentiation, blood circulation regulation and striated muscle tissue development. They were mainly enriched in cyclic guanosine phosphate (cGMP-PKG) signaling pathway, relaxin signaling pathway and PI3K/Akt signaling pathway, etc. Compared with control group, the mRNA expression levels of PI3K and eNOS in aortic tissue of rats in low-dose, medium-dose and high-dose groups were significantly reduced ( P < 0.05); the mRNA expression level of Akt in low-dose group was significantly increased ( P < 0.05). Conclusion:Fluoride exposure has certain effects on the function and gene expression of rat aortic tissue, and PI3K/Akt/eNOS signaling pathway may play an important role in the process of fluoride induced aortic tissue injury in rats.