High-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of corticotropin-releasing factor and its type-1 receptors / 中国应用生理学杂志

High-altitude hypoxia can induce physiological dysfunction and mountain sickness, but the underlying mechanism is not fully understood. Corticotrophin-releasing factor (CRF) and CRF type-i receptors (CRFR1) are members of the CRF family and the essential controllers of the physiological activity of the hypothalamo-pituitary-adrenal (HPA) axis and modulators of endocrine and behavioral activity in response to various stressors. We have previously found that high-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of CRF and CRFR1 in the brain and periphery that include activation of the HPA axis in a time- and dose-dependent manner, impaired or improved learning and memory, and anxiety-like behavioral change. Meanwhile, hypoxia induces dysfunctions of the hypothalamo-pituitary-endocrine and immune systems, including suppression of growth and development, as well as inhibition of reproductive, metabolic and immune functions. In contrast, the small mammals that live on the Qinghai-Tibet Plateau alpine meadow display low responsiveness to extreme high-altitude-hypoxia challenge, suggesting well-acclimatized genes and a physiological strategy that developed during evolution through interactions between the genes and environment. All the findings provide evidence for understanding the neuroendocrine mechanisms of hypoxia-induced physiological dysfunction. This review extends these findings.

HIF-1 signal pathway in cellular response to hypoxia / 浙江大学学报·医学版

HIF-1 is composed of HIF-1α and HIF-1β subunits. It promotes target genes transcription under hypoxia and plays essential roles in cell development, physiological adaptations, and pathological processes. In the past 10 years, the research on signaling pathways of HIF-1 in response to cell hypoxia stress, especially on HIF-1α-mediated gene transcription has made great progress.

Relationships among magnetic resonance imaging, histological findings, and IGF-I in steroid-induced osteonecrosis of the femoral head in rabbits / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To study the relationships among magnetic resonance imaging (MRI), histological findings, and insulin-like growth factor-I (IGF-I) in steroid-induced osteonecrosis of the femoral head in rabbits.</p><p><b>METHODS</b>Thirty rabbits were randomly divided into experimental Group A (n=15) and control Group B (n=15). The 7.5 mg/kg (2 ml) of dexamethasone (DEX) and physiological saline (2 ml) were injected into the right gluteus medius muscle twice at one-week intervals in animals of Groups A and B, respectively. At 4, 8 and 16 weeks after obtaining an MRI, the rabbits were sacrificed and the femoral head from one side was removed for histological study of lacunae empty of osteocytes, subchondral vessels, and size of fat cells under microscopy, and the femoral head from the other side was removed for enzyme-linked immunoadsorbent assay (ELISA) for IGF-I.</p><p><b>RESULTS</b>At 4, 8 and 16 weeks after treatment, no necrotic lesions were detected in Group B, while they were detected in Group A. Light microscopy revealed that the fat cells of the marrow cavity were enlarged, subchondral vessels were evidently decreased, and empty bone lacunae were clearly increased. The IGF-I levels in Group A were significantly higher than those in Group B. At 8 weeks after the DEX injection, the MRI of all 20 femora showed an inhomogeneous, low signal intensity area in the femoral head, and at 16 weeks, the findings of all 10 femora showed a specific "line-like sign". The MRI findings of all femora in Group B were normal.</p><p><b>CONCLUSION</b>MRI is a highly sensitive means of diagnosing early experimental osteonecrosis of the femoral head. However, the abnormal marrow tissues appeared later than 4 weeks when the expression of IGF-I increased. This reparative factor has an early and important role in response to steroid-induced osteonecrosis of the femoral head, and provides a theoretical foundation for understanding the pathology and designing new therapies.</p>

Intermittent hypoxia influence lymphocyte proliferation of rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate intermittent hypoxia effects on splenocyte mitogen-induced proliferation.</p><p><b>METHODS</b>Rats were exposured to intermittent hypoxia in a hypobaric chamber 4 h/d for 1 d, 2 d, 5 d and 15 d.</p><p><b>RESULTS</b>5 km (10.8% O2) hypoxia for 1 d significantly inhibited ConA-induced splenocytes proliferation by--74.57% +/- 7.33% (P < 0.05). Hypoxia (5 km) for 2 d, 5 d and 15 d did not markedly affect splenocyte proliferation (97.03 +/- 7.18%, 104.5% +/- 8.38%, 99.55% +/- 3.8% respectively). Hypoxia 2 km (16.0% O2) for 1 d, 2 d, 5 d and 15 d had no influence on splenocytes proliferation (93.19% +/- 11.88%, 96.43% +/- 7.9%, 99.03% +/- 10.97%, 100.54% +/- 9.54% respectively). We also demonstrated that acute hypoxia exposure (5 km) 4 h significantly suppressed DNA contents of rat splenocytes by 76.22% +/- 7.06% (P < 0.05). The suppressed DNA synthesis were returned to control level after the hypoxia for 5 d and 15 d.</p><p><b>CONCLUSION</b>These results suggest that the acute hypoxia (5 km, 4 h) induces a transient suppression on splenic lymphocyte proliferation, and the intermittent hypoxia may induce an adaptation response of the splenocytes proliferation.</p>

The effects of simulated hypoxia on the development of hypothalamic CRF and AVP neurons in postnatal rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the influence of hypoxia on postnatal developing pattern of hypothalamic corticotropin releasing factor(CRF) and arginine vasopressin (AVP) in male and female neonatal rats.</p><p><b>METHODS</b>The hypoxia was simulated in hypobaric cabin. The content of AVP and CRF was assayed by RIA method.</p><p><b>RESULTS</b>It was showed the female rats had the similar developing process with male rats, either at 2300 m or at 5000 m altitude. When they developed at simulated 5000 m altitude, the content of their hypothalamic CRF was lower than that of control rats on postnatal day 21, while the content of AVP was higher than control on day 21 and 28.</p><p><b>CONCLUSION</b>Maybe the difference of the function between hypothalamic CRF and AVP or/and the incoherence of their developing stage contribute to their particular developing pattern at 5000 m altitude.</p>

The response of hypothalamic CRF and AVP neurons of neonatal rats to simulated acute hypoxia / 中国应用生理学杂志

<p><b>AIM</b>To investigate the response of hypothalamic corticotropin releasing factor (CRF) and arginine vasopressin (AVP) of adrenalectomized neonatal rats to hypoxia.</p><p><b>METHODS</b>The hypoxia was simulated in hypobaric cabin. The amount of arginine vasopressin (AVP) and corticotropin releasing factor (CRF) was assayed by RIA method.</p><p><b>RESULTS</b>When neonatal rats exposed to acute hypoxia (simulated altitude of 5 000 m and 7 000 m, 24 h), their hypothalamic CRF was not changed in 3 d and 7 d rats, lower than control in 14 d, 21 d and 28 d rats, while hypothalamic AVP had no change in 3 d rats, was lower than control in 14 d and higher in 7 d, 21 d and 28 d rats. The responsive pattern of those two neuropeptides to acute hypoxia changed with the growth of rats. Adrenalectomy reduced the amount of hypothalamic CRF and AVP in 14 d, 21 d and 28 d rats, except AVP in 28 d rats. When adrenalectomized neonates exposed to hypoxia, there was no further change in CRF and AVE, means adrenalectomy not only removed the negative regulation of corticosteroid on CRF and AVE, but also inhibited the normal development of CRF and AVP neurons and thus, their responsive ability to hypoxia.</p>