JAK/STAT信号转导通路在大鼠急性脊髓损伤中的异常激活及意义

Abnormal Activation of JAK/STAT Signaling Pathway in Rats after Spinal Cord Injury

目的研究JAK(Janus激酶)/STAT(信号转导和转录激活子)信号转导通路相关基因JAK2、STAT3在大鼠急性脊髓损伤中激活后的表达变化,并探讨其被异常激活的意义。方法采用健康雄性SD大鼠60只,分为假手术组和脊髓损伤组,随机分到4、12、24、72h和168h各个亚组(n=6)。脊髓损伤组应用Allen’s重物坠落法并加改良制作大鼠急性脊髓损伤模型,假手术组只切除椎板不损伤脊髓。术后在相应时间处死取脊髓,HE染色观察脊髓组织形态结构,免疫组织化学检测脊髓组织中P-JAK2(磷酸化JAK2)、P-STAT3(磷酸化STAT3)表达的动态变化。结果免疫组织化学检测显示假手术组大鼠脊髓组织中P-JAK2、P-STAT3阳性细胞较少,在脊髓损伤组各个时间点P-JAK2、P-STAT3的表达量明显高于假手术组(P<0.01)。损伤后4h迅速上升,12h达峰值(P<0.01),而后逐渐下降,168h仍有表达。结论大鼠急性脊髓损伤可异常激活JAK/STAT信号转导通路,它可能在继发性脊髓损伤中起着重要作用。

Objective To explore expression changes of JAK（Janus kinase）/STATsignaling pathways related genes JAK2、STAT3after being activated in acute spinal cord injury of rats.Methods 72 healthy male SD rats were divide into two groups,the sham operation group and the spinal cord injury group;then put them into the subgroups randomly,which were 4h,12h,24h,72h and 168h（n=6）.Acute spinal cord injury rat＇s model were established by the modified Allen＇s weight drop method.The sham operation group just underwent T9 laminectomy without injuring spinal cord.The rats were sacrificed at corresponding time after operation and spinal cord tissues were taken from them.Tissues morphological structure were observed by Hematoxylin and eosin staining and the expressions of P-JAK2（phosphorylated JAK2）,P-STAT3（phosphorylated STAT3） were detected immunohistochemistry method.Rseults The low expressions of P-JAK2 and P-STAT3 were observed in the sham operation group.In the spinal cord injury group,the expressions of P-JAK2 and P-STAT3 were significantly higher than the those in sham operation group at all time points（P〈0.01）.P-JAK2 and P-STAT3 significantly increased from the 4th hour,peaking at the 12th hour after injury,then gradually decreased（P〈0.01）.Conclusion These findings suggest that JAK/STAT signaling pathway is abnormally activated in spinal cord injury at the acute stage,and this pathway may play an important role in the secondary spinal cord injury.