关键词: 孤独症谱系障碍, 发病机制, 信号通路, 钙调蛋白激酶Ⅱ, 细胞外信号调节激酶, 鼠模型

Abstract: Objective To explore the role of calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ )and extracellular signal-regulated kinase ( ERK) in the pathogenesis of autism spectrum disorders. Methods Female Sprague-Dawley rats were given a single intraperitoneal injection of sodium valproate (VPA,600 mg/kg) on 12.5 d after pregnancy,and their offspring were as the model group; while the other pregnancy rats were given normal saline,and their offspring were as the control group.Both groups were observed with the HE staining,immunohistochemistry of CaMK Ⅱ and ERK and image analysis 1,7,14 d and 28 d after birth. Results Compared with the control group,HE staining showed the number of cortical neurons decreased on 1 d and 7 d after birth in the model group,rapidly increased on 14 d after birth,and maintained in high level on 28d after birth.For immunohistochemistry,the integrated optical density (IOD) of CaMKⅡ and ERK were increased in cortex on 1~14 d after birth (P<0.001) in both groups,and were stable 28 d after birth (P>0.05).Compared with the control group,the IOD of CaMK Ⅱ and ERK increased much more at every time point (P<0.001) in the model group.CaMK Ⅱ and ERK were increased on 1 d,7 d (P<0.001),significantly increased on 14 d (P<0.001),and tended to be stable on 28 d after birth (P>0.05). Conclusion The expression of CaMKⅡ and ERK of cerebral cortex neurons increases in the autism model rats,especially in the early time.

Key words: autistic spectrum disorders, pathogenesis, signal pathway, calmodulin-dependent protein kinase Ⅱ, extracellular signal-regulated kinase, rat model