新生大鼠缺氧缺血性脑损伤血红素氧化酶-1表达与脑细胞凋亡的关系

Relationship between expressions of heme oxygenase-1 and brain cell apoptosis after hypoxic-ischemia brain damage in neonatal rats

目的 探讨新生大鼠缺氧缺血性脑损伤 (HIBD)后海马区血红素氧化酶 1(HO 1)的表达 ,以及与细胞凋亡的关系。方法 7日龄SD仔鼠 72只 ,随机分为HIBD组和假手术对照组。用原位杂交和免疫组化观测两组在不同时间点海马区HO 1mRNA及蛋白阳性细胞数量变化 ;用原位缺口末端标记 (TUNEL)法检测凋亡的脑细胞。结果 1.HIBD组右侧海马HO 1mRNA表达 4h开始升高 (P <0 .0 5 ) ,12h达高峰 ,4 8h开始略有下降 ,72h后仍高于对照组 (P <0 .0 1)。 2 .HO 1蛋白表达与HO 1mRNA表达变化规律相一致。 3.凋亡检测发现 ,HIBD组右侧海马 12h凋亡细胞数增加 ,2 4h已有明显细胞凋亡 (P <0 .0 1) ,72h凋亡细胞减少 ,仍高于对照组 (P <0 .0 5 )。结论 新生大鼠HIBD后HO 1mRNA及其蛋白表达增加 。

Objective To study expressions of heme oxygenase-1 mRNA and protein in rat hippocampus after hypoxic-ischemia brain damage(HIBD) as well as the relationship with apoptosis in brain.Methods Seven-day-old SD rats were randomly divided into hypoxic-ischemia brain damage group and sham control group.Expressions of HO-1 protein and mRNA as welll as the relationship with apoptosis after HIBD in neonatal rat were determined by immunohisochemistry and in situs hybridizaion as well as terminal deoxynucleotidy transferase mediated UTP-biotin nick end labeling(TUNEL).Results 1.In the right hippocampus,expression of HO-1 gene increased sharply at 4 h (P<0.05) after hypoxic-ischemia brain damage,reaching the peak from 12 h to 24 h,and then decreased gradually after 48 h,which was still higher than that in sham control group at 72 h(P<0.01). 2.The obvious increase in HO-1 protein was parallelced with the increase in mRNA levels;3.Apoptosis of neurons in CA3 region was obviously observed at 24 h after HIBD and then decreased at 72 h, which was still higher than that in sham control group (P<0.05).Conclusion Expressions of heme oxygenase-1 in rat's hippocampus may increase after hypoxic-ischemia brain damage, which suggests that HO-1 is associated with hypoxic-ischemia neuronal apoptosis.