Study on the characteristic plasticity and preventive mechanisms against neonatal brain damage.

血红素加氧酶-1(HO-1)是血红素分解代谢中的一种诱导性酶，能分解血红素形成胆绿素、一氧化碳和铁。虽然HO-1在正常鼠脑中只在基础水平表达，但HO-1的表达是对各种树桩的强烈激活反应。我们研究了7日龄大鼠缺氧缺血性脑损伤模型中HO-1mRNA和蛋白水平的定量变化。HO-1蛋白在海马区结扎侧最高，伤后12h达高峰。HO-1mRNA的表达在缺氧缺血结束时已经升高，在缺氧缺血后3h达到最大值，然后下降。HO-1蛋白表达的时间进程与HO-1基因表达的时间进程基本一致。在新生大鼠缺氧缺血模型中，与成年大鼠相比，HO-1蛋白的表达被诱导得更早。158为了阐明HO-1对发育中的脑细胞的生物学作用，我们分析了热休克(42度，30分钟)诱导的HO-1对神经胶质细胞分化的影响。大鼠脑胶质瘤细胞株C6在维甲酸作用下可表达蛋白脂蛋白(PLP)，在DBcAMP作用下可表达胶质纤维酸性蛋白(GFAP)。热休克处理可抑制C6细胞PLP的表达，增强GFAP的表达。热休克蛋白，包括HO-1，可能干扰神经胶质细胞的分化，导致围产期脑白质损伤。HO-1对氧化应激的防御机制在HI早期就开始在脆弱的围产期脑内发挥作用，可能有助于保护围产期因缺氧和缺血而引起的脑损伤。然而，诱导的热休克蛋白可能会影响神经胶质细胞的分化，导致脑白质损伤。

Heme oxygenase-1 (HO-1) is an inducible enzyme in heme catabolism that cleaves heme to form biliverdin, carbon monoxide and iron. Although HO-1 is only expressed at a basal level in the normal rodent brain, the expression of HO-1 is strongly activated response to various stumuli. We investigated the quantitative changes in HO-1 mRNA and protein levels in 7-day-old rat model of hypoxic-ischemic (HI) brain damage. The amount of HO-1 protein was the highest on the ligated side of the hippocampus, and it increased to a maximum at 12 hrs following HI insult. The level of HO-1 mRNA had already increased by the end of HI, reached a maximum at 3 hrs following HI insult and then decreased. The time course of the HO-1 protein induction was essentially consistent with that of HO-1 mRNA.In the newborn hypoxic-ischemic rat model, the expression of HO-1 is induced at an earlier stage compared to that in the adult ischemic rat model. 158To clarify the biological effects of HO-1 against developing brain cells, we analyzed the influence of HO-1 induced by heat shock treatment (42 degree, 30 min) on glial differentiation. Rat glioma cell line, C6, can express both proteolipid protein (PLP) with retinoic acid treatment and glial fibrillary acidic protein (GFAP) with dbcAMP treatment. Heat shock treatment suppressed PLP expression and enhanced GFAP expression in C6 cells. Heat shock proteins, including HO-1, may interfere the glial differentiation resulting in perinatal white matter lesion.Defense mechanism of HO-1 against oxidative stress begins to work at the early stages of HI insult in the vulnerable perinatal brain and may contribute to protect against brain damage resulting from a combination of hypoxia and ischemia during the perinatal period. However, induced heat shock proteins may affect the glial differentiation leading to white matter lesion.