c-jun在围产期缺血缺氧脑损伤后的表达及其与神经元凋亡关系的研究

The relationship between the expression of c jun mRNA and neurons apoptosis following perinatal ischemic hypoxia

目的探讨围产期缺血缺氧脑损伤后即刻早期基因（ｃｊｕｎ）的表达变化规律及其与神经元凋亡的关系。方法通过结扎Ｗｉｓｔａｒ孕鼠一侧子宫角血管（其宫内胎鼠作为对照），建立围产期缺血缺氧脑损伤动物模型。采用原位杂交及原位末端标记法观察剖宫产后存活不同时间大鼠大脑ｃｊｕｎｍＲＮＡ的表达及神经元凋亡的情况。结果缺血后１５分钟，大脑皮层和海马ＣＡ３区即出现ｃｊｕｎｍＲＮＡ的表达，随时间延长，表达量逐渐增加，至１～２小时，杂交信号最强，４小时后逐渐减弱，但到２４小时，ｃｊｕｎｍＲＮＡ表达又出现第二次高峰，以后逐渐减弱，至３天基本消失；对照组仅在生后２４小时海马有较少量的表达。并发现缺血后２天神经细胞凋亡数明显多于对照组。结论宫内缺血缺氧可使ｃｊｕｎ的表达增强和凋亡细胞增加，ｃｊｕｎ的改变可能引起了其后续与细胞凋亡相关基因的转录，从而导致细胞凋亡的发生。

Objective To investigate the relationship between c jun mRNA and neurons apoptosis following perinatal ischemic hypoxia. Methods The authors set up a fetal rat model of perinatal ischemic hypoxia by ligating unilateral uterine horn vessel of pregnant Wistar rats . The contralateral horn vessel was not ligated and those fetuses served as controls. Rat pups were delivered by cesarean section at the end of ischemic hypoxic insult and then the rats' brain tissues were collected at different time. In situ hybridization and in situ end labeling methods were used to detect c jun mRNA and neurons apoptosis separately. Results The results showed that the expression of c jun mRNA began at 15 minutes, peaked at 1 2 hours after ischemic hypoxic insult and reduced gradually by 4 hours. The expression of c jun mRNA reached another peak at 24 hours after the insult and then disappeared gradually till 72 hours. Only a slight hybrid signals could be found at the time of one day in hippocampus in the control group. Meanwhile, the number of cells with apoptosis at two days after ischemic hypoxia was much more than that in the control group. Conclusion These results indicated that the increase in expression of immediate early gene c jun and then the cell apoptosis could be induced by perinatal ischemic hypoxia. The expression of c jun mRNA might induce the transcription of its target gene, especially, some “genes promoting apoptosis”.