高温高湿应激对大鼠海马HPA轴负反馈调节的影响

IF 0.6 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Neuro endocrinology letters Pub Date : 2021-09-10
Min Yang, Yong Luo, Xin-Zhong Hao, Ming-Yang Guo, Wan Li, Yong-He Hu
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引用次数: 0

摘要

目的研究高温高湿胁迫下大鼠海马对下丘脑-垂体-肾上腺(HPA)轴的负反馈调节:将30只SD雄性大鼠随机分为三组:对照组、高温高湿组和药物干预组。对照组大鼠在温度为 24 ± 1°C、湿度为 50 ± 5%的环境中饲养,不进行任何刺激。其他组大鼠每天暴露在高温高湿环境中 4 小时,温度为 35±1 ℃,湿度为 85±5%。药物干预组大鼠胃内注射糖皮质激素受体拮抗剂米非司酮。给药持续 3 周。3 周后,用 ELISA 法检测大鼠血清中促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)和皮质酮(CORT)的水平。免疫组化和原位杂交法分别检测了海马中皮质类固醇受体(MR)、糖皮质激素受体(GR)、诱导型一氧化氮合酶(iNOS)、瞬时受体电位类香草素1(TRPV1)和11β-羟基类固醇脱氢酶1(11β-HSD1)的蛋白和mRNA水平。用 TUNEL 细胞凋亡染色法检测海马细胞的凋亡情况:高温高湿应激3周后,高温高湿组血清中CRH、ACTH和CORT水平较对照组显著升高;药物干预组血清中CRH、ACTH和CORT水平较高温高湿组显著降低(P0.05),而TRPV1 mRNA水平显著升高(P0.05)。与对照组相比,高温高湿组海马细胞凋亡明显增加(P0.05):结论:高温高湿应激可上调海马局部 iNOS 的表达,降低糖皮质激素(GC)受体的活性,从而减少 GR-GC 的有效结合,抑制海马对 HPA 轴的负反馈调节。糖皮质激素受体拮抗剂能改善大鼠海马对 HPA 轴的负反馈调节。
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Effects of high temperature and high humidity stress on the negative feedback regulation of hippocampus on HPA axis in rats.

Objective: To investigate the negative feedback regulation from rat hippocampus on hypothalamic-pituitary-adrenal (HPA) axis under high temperature and high humidity stress.

Methods: Thirty (30) SD male rats were randomly divided into three groups: control group, high temperature and high humidity group, drug intervention group. The rats in control group were kept in the environment with temperature of 24 ± 1°C and humidity of 50 ± 5%, without any stimulation. The rats in the other groups were exposed to high temperature and high humidity environment for 4 h each day, with temperature of 35±1 °C and humidity of 85±5%. The rats in drug intervention group were intragastrically administered with the glucocorticoid receptor antagonist mifepristone. The administration was continued for 3 weeks. After 3 weeks, the serum levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected by ELISA.The protein and mRNA levels of corticosteroid receptors (MR), glucocorticoid receptors (GR) and inducible nitric oxide synthase (iNOS), transient receptor potential vanilloid 1 (TRPV1) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in hippocampus were determined by immunohistochemistry and in situ hybridization, respectively. The apoptosis of hippocampal cells was examined with TUNEL apoptosis staining.

Results: After stimulation with high temperature and high humidity stress for 3 weeks, the serum levels of CRH, ACTH and CORT in the high temperature and high humidity group were significantly increased compared to that of control group; the levels of these indicators in drug intervention group were decreased compared to that of high temperature and high humidity group (P<0.05). In high temperature and high humidity group, the protein and mRNA levels of MR, GR, iNOS in hippocampus of rats were significantly increased compared with that of control group (p<0.05); and the levels of these indicators in drug intervention group were lower than that of high temperature and high humidity group (p<0.05). In addition, compared with the control group, the TRPV1 protein level in hippocampus of rats in high temperature and high humidity group was not significantly changed (p>0.05), while the TRPV1 mRNA level was significantly increased (p<0.05). Neither the protein nor mRNA levels of 11β-HSD1 showed significant difference compared to control group (p>0.05). The apoptosis of hippocampus cells in the high temperature and high humidity group was significantly increased compared with that of control group (p<0.05); and it was lower in the drug intervention group than that of in high temperature and high humidity group while the result was not significant (p>0.05).

Conclusion: High temperature and high humidity stress may up-regulate the local expression of iNOS in hippocampus and decrease the activity of glucocorticoids (GC) receptor, then the effective binding of GR-GC would be decreased and the negative feedback regulation of hippocampus on HPA axis would be inhibited. The glucocorticoid receptor antagonist can improve the negative feedback regulation of hippocampus on HPA axis in rat.

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来源期刊
Neuro endocrinology letters
Neuro endocrinology letters 医学-内分泌学与代谢
CiteScore
1.00
自引率
14.30%
发文量
24
审稿时长
6 months
期刊介绍: Neuroendocrinology Letters is an international, peer-reviewed interdisciplinary journal covering the fields of Neuroendocrinology, Neuroscience, Neurophysiology, Neuropsychopharmacology, Psycho­neu­ro­immunology, Reproductive Medicine, Chro­no­biology, Human Ethology and re­lated fields for RAPID publication of Original Papers, Review Articles, State-of-the-art, Clinical Reports and other contributions from all the fields covered by Neuroendocrinology Letters. Papers from both basic research (methodology, molecular and cellular biology, anatomy, histology, biology, embryology, teratology, normal and pathological physiology, biophysics, pharmacology, pathology and experimental pathology, biochemistry, neurochemistry, enzymology, chronobiology, receptor studies, endocrinology, immunology and neuroimmunology, animal phy­siology, animal breeding and ethology, human ethology, psychology and others) and from clinical research (neurology, psychiatry and child psychiatry, obstetrics and gynecology, pediatrics, endocrinology, immunology, cardiovascular studies, internal medicine, oncology and others) will be considered. The Journal publishes Original papers and Review Articles. Brief reports, Special Communications, proved they are based on adequate experimental evidence, Clinical Studies, Case Reports, Commentaries, Discussions, Letters to the Editor (correspondence column), Book Reviews, Congress Reports and other categories of articles (philosophy, art, social issues, medical and health policies, biomedical history, etc.) will be taken under consideration.
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