1.To explore the effect of high-altitude hypoxia on thyroid hormone synthesis based on metabolomics
Chongyang Dai ; Xue Lin ; Yaxuan Wang ; Xiaoyan Pu
Acta Universitatis Medicinalis Anhui 2024;59(11):1989-1997
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 hypobaric 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 levels 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-κB/p65(NF-κB/p65) and tumor necrosis factor-α(TNF-α) were detected by RT-PCR, Western blot and ELISA. The expression levels of Pro apoptotic protein Bcl-2 associated X protein(Bax) and inhibitor of apoptosis protein B-cell lymphoma/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, PaO2and SaO2of 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 T4decreased 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 T4content were completely consistent with the above 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 levels 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 oxidative stress and inflammatory response, which effects thyroid function and ultimately reduces thyroid hormone synthesis.
2.Effects of Kaixin Powder on Learning and Memory Function and ATP/AMP Ratio in Rats with Multiple Infarct Dementia
Yuan DAI ; Chongyang SHEN ; Ying FU ; Yueqiang WEN ; Shijun XU
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(12):2180-2184
Objective: To investigate the effects of Kaixin Powder on learning and memory, ATP/AMP ratio, GABA andiNOS levels in rats with multiple infarct dementia. Methods: The rat model of multi-infarct dementia was established bymicro-thromboembolism. Morris water maze and opening experiment were used to evaluate learning and memoryfunction. The pathological changes of hippocampal CA1 area were evaluated by HE staining. The contents of ATP andAMP in brain tissue were determined by HPLC. The content of γ-aminobutyric acid and iNOS in peripheral blood weredetected by ELISA kit. Results: Compared with the rats of model group, rats of Kaixin Powder group can significantlyshorten the escape latency, increase the number of crossing platforms, Results: Compared with the model group, increasethe standing times in the opening experiment, prolong the exercise time, shorten the resting time, improve the nerve celldamage in the hippocampal CA1 area, and significantly increase the ratio of ATP/AMP of brain tissue, decreased brainGABA content and serum iNOS content (P < 0.05) . Conclusion: Kaixin Powder has the effect of improving learning andmemory function and abnormal motor behavior in rats with multiple infarct dementia. The mechanism is related toreducing GABA and i NOS content in brain tissue, increasing ATP/AMP ratio in brain tissue and improving energysupply in brain tissue.