| Background and Objective Hypoxic stress can cause a series of physiological adaptation changes.Hypoxia affected synthesis and secretion of the hormones,neurotransmitters and small molecule compounds of the hypothalamus-pituitary-thyroid(HPT)axis,which participate in the physiological regulation of hypoxia stress.Intestinal flora changes under the influence of the host and influences the physiological function of the host by regulating the metabolites.Currently,the interaction between HPT axis and intestinal flora under low oxygen environment has not been reported.Therefore,the effects of hypoxia on the HPT axis and intestinal flora and their interactions were investigated by establishing a low-pressure and hypoxic animal model.Methods The hypoxic model of adult male SD rats was established by hypobaric chamber with simulatd altitude of 5,500m.The hypoxic groups were set for 1,3,7,14,21 and 28 days,and the normoxic recovery group were set for 1 and 3 days after hypoxia.Daily body weight and intake were recorded.HTP axis hormones and stress hormones in serum were detected by ELISA.Thyroid morphology was observed by HE staining.Expression of HPT axis hormone receptor,deiodinase 2 and HIF-1a in pituitary and thyroid were detected by qPCR and western blot.Intestinal flora was analyzed by 16s rDNA sequencing.The metabolites in faeces and serum of the 3-day groups were determined by LC-MS.The correlation between intestinal flora and metabolites and serum HPT axis hormone was analyzed by spearman correlation analysis.Results The body weight(p<0.001)and food intake were significantly reduced.In the 1-day and 3-day groups,TRH and TSH significantly decreased(p<0.05),TT4,TT3,FT4 and FT3 were significantly increased(p<0.05),and TSH receptor,DIO2,and HIF-1a expression were significantly increased(p<0.05),and the abundance of Prevotella was significantly decreased(p<0.05),Parabacteroides,Lactobacillus,Butyricimonas,Bacteroides,Odoribacter and RC4-4 were significantly increased(p<0.05).The changes during acute hypoxia could be restored to the control group in the normal environment.In the 14-day,21-day and 28-day hypoxia groups,the common intestinal and serum metabolites were significantly decreased(p<0.05),and the cadinene was positively correlated with RC4-4 and TRH(p<0.05),the number of inactive thyroid follicular was increased,TRH and TSH were significantly decreased(p<0.05),and TT4 and TT3 were significantly increased(p<0.05),and there was no significant difference in other indexes,the abundance of Parabacteroides,Sphaerochaeta,Akkermansia,Elusimicrobium increased significantly,but Lactobacillus and Sutterella decreased significantly(p<0.05).Butyricimonas,Elusimicrobium and Sutterella were significantly negatively correlated with TRH and TSH,(p<0.05)Prevotella.Bacteroides,Odoribacter and Parabacteroides was significantly correlated with TSH,TT4,TT3 and FT4(p<0.05),respectively.Lactobacillus was significantly correlated with TRH,TSH and FT4(p<0.05).Akkermansia was significantly correlated with TRH,FT4(p<0.05).RC4-4 was significantly associated with TSH,TT3(p<0.05).Conclusion Hypoxic stress at an simulate altitude of 5500m could induce adaptive changes in the thyroid function of SD rats,and the changes were influenced with hypoxia exposure time.Hypoxic stress could significantly affect the intestinal flora structure and relative abundance of some flora and cause significant changes in some metabolites in the faeces and serum.The correlation analysis of intestinal flora and its metabolites with HPT axis hormone showed that the intestinal flora may affect TRH,TSH,TT4,TT3,FT4 and FT3 of the HPT axis through its metabolites in the circulatory system. |
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