Summary： This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment （VCI） with the goal of providing a target for t...Summary： This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment （VCI） with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography （CT） were recruited as the ischemic cerebrovascular diseases （ICVD） group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay （ELISA） was employed to detect the levels of hypoxia-inducible factor 1-alpha （HIF-1α）, vascular endothelial growth factor （VEGF）, nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination （MMSE） score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group （P=-0.037 and P=0.000; P=0.023 and P=-0.005）. In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid （r=-0.327, P=0.021; r=-0.585, P=0.046）. In VCI group, HIF-1α level was correlated with NGF level （r=0.589, P=0.044）. HIF-1α and NGF are involved in ischemic and hy- poxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.展开更多
目的:研究不同低氧暴露时间对小鼠骨骼肌雌激素受体相关受体(estrogen receptor related receptorsα,ERRα)与丙酮酸脱氢酶激酶4(PDK4)DNA结合活性及PDK4基因表达的影响,以探讨低氧条件下影响糖代谢及其信号分子之间的相互调节可能的...目的:研究不同低氧暴露时间对小鼠骨骼肌雌激素受体相关受体(estrogen receptor related receptorsα,ERRα)与丙酮酸脱氢酶激酶4(PDK4)DNA结合活性及PDK4基因表达的影响,以探讨低氧条件下影响糖代谢及其信号分子之间的相互调节可能的机制。方法:野生小鼠随机分为常氧组、低氧组(氧浓度11.25%左右,模拟海拔高度4 500m),而后又进一步分为0天、7天、14天、28天组,每组10只。低氧暴露时间为每天8h。同天数的小鼠常氧组与低氧组脱颈处死。染色质免疫共沉淀法(Chip)测定ERRα/PDK4结合活性,Real-Time PCR测定骨骼肌PDK4mRNA含量。结果:1)随着天数增加,低氧组ERRα/PDK4的结合活性有增加的趋势,但没有显著性差异;2)随着天数增加,低氧28天组PDK4mRNA相对表达量与0天组相比显著性升高(P<0.05),且与28天常氧组相比也有显著性增加(P<0.05)。结论:低氧28天小鼠骨骼肌PDK4mRNA相对表达量显著增加,但其ERRα/PDK4的结合活性并没有显著性变化,推测低氧下ERRα并不是促进PDK4mRNA表达的主要转录因子。展开更多
基金supported by the National Natural Science Foundation of China (No. 81171029)
文摘Summary： This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment （VCI） with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography （CT） were recruited as the ischemic cerebrovascular diseases （ICVD） group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay （ELISA） was employed to detect the levels of hypoxia-inducible factor 1-alpha （HIF-1α）, vascular endothelial growth factor （VEGF）, nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination （MMSE） score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group （P=-0.037 and P=0.000; P=0.023 and P=-0.005）. In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid （r=-0.327, P=0.021; r=-0.585, P=0.046）. In VCI group, HIF-1α level was correlated with NGF level （r=0.589, P=0.044）. HIF-1α and NGF are involved in ischemic and hy- poxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.
