血晶素对缺氧缺糖海马脑片的保护作用及其分子机制

目的观察血晶素（Hemin）对海马脑片氧糖剥离（OGD）模型的保护作用并探讨其机制。方法取新生8～10dSD大鼠，制备厚约400μm海马脑片，培养2周后筛取完好无特异荧光着色的脑片，分为正常培养对照组（HOTC）、缺氧缺糖组（OGD）、预加Hemin再缺氧缺糖组（Hemin＋0GD）和预加血红素加氧酶-1（Heme oxygenase-1，HO-1）抑制剂锌原卟啉（Znpp）再缺氧缺糖组（Znpp＋OGD）。除HOTC组外，其余各组在5％C02、95％N2的混合气体中培养1．5小时，其后恢复培养24小时。海马脑片冰冻连续冠状切片，应用免疫组织化学染色和图像分析处理技术观察海马脑片脑红蛋白（Neuroglobin，Ngb）和HO-1表达变化，并观察神经元形态学改变。结果海马脑片发生缺氧缺糖时，神经元中Ngb蛋白和HO-1蛋白表达增加，血晶素促进神经元Ngb蛋白和HO-1蛋白表达，并减轻海马脑片缺糖缺氧性损伤。Znpp抑制神经元Ngb蛋白和HO-1蛋白表达，并加重海马脑片缺糖缺氧性损伤。结论血晶素可减轻海马脑片缺糖缺氧性损伤，其机制可能通过诱导HO-1表达从而增加神经元Ngb表达发挥作用。

Neuroprotective effect of hemin and its molecular mechanism in the hippocampal organotypic tissue cultures after combined oxygen/glucose deprivation

Objective To investigate the neuroprotective role of hemin and its effect on the expression of neuroglobin（Ngb） and heme oxygenase-1 （HO-1） in the hippocampal organotypic tissue cultures （HOTC） after combined oxygen/ glucose deprivation（OGD）. Methods SD rats, 8-10-days old, were sacrificed for brain. HOTC were made and randomly divided into four groups, including HOTC, HOTC undergoing OGD （OGD）, HOTC undergoing OGD following pretreatment with hemin （Hemin ＋ OGD） and HOTC undergoing OGD following pretreatment with Znpp（Znpp＋ OGD）. The expression of neuroglobin and HO-1 was detected with immunohistochemical technique and computer-assisted image analysis. Results In OGD group, hippocampal organotypic tissue lost normal structure and neurons were damaged severely, and the expression of Ngb protein and HO-1 protein were significantly stronger than that in the HOTC group. Pretreatment with hemin could effectively reverse the damage of the neurons, and accompanied with upregulation of Ngb protein and HO-1 protein expression. In contrast, pretreatment with Znpp, an HO-1 inhibitor, could aggravate the damage, and accompanied with reduction of Ngb protein and HO-1 protein expression. Conclusion Hemin has protective effect on injury induced by OGD in rat hippaocampal slices, which is associated with enhanced expression of neuroglobin via the upregulation of HO-1.