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.

Clinical significance of venous return disturbance in patients with osteonecrosis of femoral head / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the correlation of venous return disturbance (VRD), bone marrow edema (BME) and the amount of joint fluid with clinical symptoms in osteonecrosis of the femoral head (ONFH).</p><p><b>METHODS</b>Twenty patients (25 hips) with ONFH proved by pathology were parallelly examined by 1.5 T MR and medullograph.</p><p><b>RESULT</b>In total 25 hips VRD was observed in 16 hips with medullograph and 13 hips with the clinical symptoms (P <0.05). BME was found in 17 with MRI (P <0.01), and the was found in 15 hips with MRI (Spearman=0.949). VRD were found in 16 hydrarthrus.</p><p><b>CONCLUSION</b>ONFH patients with clinical symptoms have VRD, BME and the hydrarthrus. The medullograph is of value in monitoring the development of ONFH.</p>

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>