To explore the effect of high-altitude hypoxia on thyroid hormone synthesis based on metabolomics
Objective To explore the effects of high-altitude hypoxia on thyroid hormone(TH)synthesis by quasi-targeted metabolomics technology.Methods Twenty SPF male SD rats were randomly divided into Control group and Hypoxia group.An acute hypoxia injury model was established in SD rats by simulating hypoxia stress in a hy-pobaric oxygen chamber at an altitude of 6 km for 48 hours.The body weight,arterial oxygen partial pressure(PaO2)and blood oxygen saturation(SaO2)were detected.KEGG enrichment analysis was performed after the metabolites in the blood of two groups were detected by quasi-targeted metabolomics technology.The expression lev-els of sodium iodide symporter(NIS),thyroid peroxidase(TPO)and thyroglobulin(TG)were detected by RT-PCR and Western blot in TH synthesis pathway.The content of serum thyroxine(T4)and the expression levels of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and malondialdehyde(MDA)were detected by ELISA.The expression levels of toll-like receptors-4(TLR-4),interleukin-6(IL-6),nuclear factor-KB/p65(NF-κB/p65)and tumor necrosis factor-α(TNF-α)were detected by RT-PCR,Western blot and ELISA.The expres-sion levels of Pro apoptotic protein Bcl-2 associated X protein(Bax)and inhibitor of apoptosis protein B-cell lym-phoma/leukemia-2(Bcl-2)were detected by RT-PCR and Western blot in rats thyroid tissue.Results Compared with the Control group,the body weight,PaO2 and SaO2 of rats in the Hypoxia group significantly decreased(P＜0.01).The differential metabolites in arterial serum of hypoxia group rats were significantly enriched in the TH synthesis pathway,and the content of the pathway end product T4 decreased significantly(P＜0.01).In addition,the mRNA and protein expression levels of NIS,TPO,TG in rats thyroid tissue significantly decreased(P＜0.05).The ELISA validation results showed that the changes of T4 content were completely consistent with the a-bove results.Compared with the Control group,the enzyme activities of SOD and GSH-Px in the serum of rats in the hypoxia group decreased,while the content of MDA increased(P＜0.01);the mRNA,protein expression lev-els and contents of TLR-4,IL-6,NF-κ B/p65,TNF-α significantly increased(P＜0.05),while the mRNA and protein expression levels of Bax in thyroid tissue significantly increased,Bcl-2 significantly decreased(P＜0.05).Conclusion Hypoxia stress at high altitude leads to apoptosis of thyroid follicular epithelial cells by promoting oxi-dative stress and inflammatory response,which effects thyroid function and ultimately reduces thyroid hormone syn-thesis.
万方数据
维普
