脑室周围白质软化新生大鼠酪氨酸蛋白激酶-信号转导和转录激活因子信号转导与神经再生的关系

Relationship of Janus Kinase-Signal Transducers and Activator of Transcription Signal Transduction and Neurogenesis in Neonatal Rats with Periventricular Leukomalacia

目的观察新生大鼠脑室周围白质软化(PVL)模型侧脑室室管膜下区和脉络丛酪氨酸蛋白激酶(JAKs)-信号转导和转录激活因子(STATs)信号转导途径与神经再生的关系。方法采用右侧颈总动脉结扎并60mL/L氧气处理4h,建立2日龄SD大鼠脑缺氧缺血(HI)PVL模型;对照组仅予分离右侧颈总动脉,不进行结扎和缺氧处理。HI后0h、3h、6h、12h、1d、3d、7d处死动物,用免疫组织化学方法检测其侧脑室室管膜下区和脉络丛磷酸化的STAT3(P-STAT3)、巢蛋白(Nestin)表达。Image-Pro Plus6.0图像分析系统测定积分光密度(IOD)、总表达面积,计算平均光密度(MOD),高倍镜下行Nestin阳性细胞计数。结果对照组大鼠侧脑室室管膜下区和脉络丛P-STAT3、Nestin表达量少。实验组大鼠HI后,P-STAT3、Nestin水平表达明显升高,P-STAT3、Nestin在HI后即刻就有表达,分别于1d和3d达到高峰,7d仍高于对照组水平,各时间点组间比较差异有统计学意义(Pa<0.01)。结论HI后侧脑室室管膜下区和脉络丛JAKs-STATs信号转导途径被激活,该途径可能参与PVL的神经再生过程。

Objective To observe the relationship of the Janus kinasc - signal transducers and activator of transcription pathway and neurogenesis in the lateral ventricle subventrieular zone（SVZ） and ehoroid plexus of neonatal rats with periventricular leukomalacia（PVL）. Methods PVL models were established by right common carotid artery ligation followed by 4 h 60 mL/L oxygen exposure in 2 - day - rat; the neonatal rats performed a sham operation, without hypoxia -ischemia were used as control group. The rats were sacrificed at 0 h ,3 h ,6 h, 12 h, 1 d ,3 d and 7 d after hypoxic -ischemic （HI） , and brain tissues were collected ,immunohistochemistry was used to detect the expression of P - STAT3 and Nestin in the subventricular zone and choroid plexus. Results Very low expressions of P - STAT3 and Nestin were ob- served in lateral ventricle SVZ and choroid plexus in control group. The expression levels of P- STAT3 and Nestin increased：significantly after HI,peaked at I d and 3 d separately, and remained at a higher level at 7 d after HI, demonstrating significant differences at each time point compared with those in control group （ Pa 〈 0.01 ）. Conclusions HI resulted in the activation of JAKs - STATs pathway in the subventricular zone and choroid plexus,and this pathway might participate in the neurogenesis process of periventrieular leukomalacia.