急性低氧条件下复氧后大鼠脑HIF-1α蛋白的表达与药物干预研究

目的 观察大鼠脑缺氧状态下HIF-1α蛋白的表达规律及低氧状态下人参皂甙Rd干预对其影响并探讨机理。方法 将成年Wistar大鼠随机分为常氧对照组、急性低氧对照组、低氧预处理干预组、人参皂甙Rd干预组，分别观察各组大鼠海马锥体细胞层神经元形态的变化及HIF-1α蛋白的表达规律。结果 在缺氧后复氧即刻，我们可以发现HIF-1α蛋白的少量表达，主要存在于海马细胞，多在细胞质中表达；随着时间的推移，在复氧后4小时，HIF-1α表达逐渐达高峰，至9小时HIF-1α表达又明显减少。低氧预处理干预组及人参皂甙Rd干预组的实验结果发现HIF-1α表达较非干预组减少，与非干预组各时间点相比，均有统计学意义（P=0.009＜0.05）。两个干预组之间比较无统计学差异(P＞0.05)。结论 急性低氧可以促使HIF-1α在大鼠海马神经细胞的表达，具有时间依赖性；同时，低氧预处理干预及人参皂甙Rd干预均可促使大鼠脑组织HIF-1α表达减少，可能对急性缺氧性脑损伤产生保护作用，抑制氧自由基的产生及调节钙离子内流可能是低氧预处理及人参皂甙Rd的作用途径之一，其具体机理有待进一步阐明。

Expression of HIF-1α after acute cerebral hypoxia-reoxygen in rats and ginsengoside Rd in-terference

Objective: To observe the expression of HIF-1α in cerebral hypoxia rats and the effect by ginsenoside Rd interference as well as to explore its possible mechanism. Methods: 50 adult wistar rats were divided into 4 groups: normal oxygen control group, acute hypoxia group, hypoxia pretreatment group and ginsenoside Rd interference group; to observe the change of hippocampus cell shape and the expression of HIF-1α in every group. Results: At immediate reoxygen time, we can found a few expression of HIF-1α protein which mostly consisted in hippocampus cell, much of them in cytoplasm; as time processed, the expression level of HIF-1α reached the peak at reoxygen 4h; the expression level of HIF-1α markedly decreased at reoxygen 9h, there is statistical differences for AOD values between control group and interference groups. (P =0.009<0.05); there is no statistical differences between two interference groups(P>0.05). Conclusion: Acute hypoxia can cause the expression of HIF-1α in rat hippocampus cells and its expression has time dependence; at the same time, hypoxia pretreatment and ginsenoside Rd interference can make the expression of HIF-1α decreased; the regulation of Ca2+ influx and the inhibition of oxygen free radicals may be one of its mechanism; it suggested that these pretreatment measures may have protective action for acute hypoxia cerebral injury, the concrete mechanism still to be clarified.