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目的探讨钙调蛋白激酶Ⅱ(CaMKⅡ)和细胞外信号调节激酶(ERK)在孤独症谱系障碍发病中的作用。方法孕12.5 d Sprague-Dawley孕鼠腹腔注射丙戊酸钠600mg/kg建立子代孤独症谱系障碍模型大鼠,对照组注射同等剂量生理盐水。利用HE染色、免疫组化和图像分析技术观察比较出生后1、7、14d和28d两组大鼠脑部CaMKⅡ、ERK表达情况。结果 HE染色:出生后1d、7d模型组神经元数量较少,出生14d后剧增,出生后28d仍高于对照组。免疫组化:出生后1~14d两组CaMKⅡ、ERK表达均显著升高(P<0.001),出生28d后表达趋于稳定(P>0.05);与对照组相比,模型组各日龄大鼠CaMKⅡ、ERK表达水平均增高(P<0.001);CaMKⅡ、ERK于出生后1d、7d表达显著升高(P<0.001),出生后14d表达量最多(P<0.001),出生28d后趋于稳定(P>0.05)。结论孤独症谱系障碍模型大鼠大脑皮层CaMKⅡ、ERK的表达增加,尤其是在出生后早期。
Objective To investigate the role of calcineurin Ⅱ (ERK) and extracellular signal-regulated kinase (ERK) in the pathogenesis of autism spectrum disorders. Methods Pregnant 12.5-d Sprague-Dawley pregnant rats were injected intraperitoneally with sodium valproate 600mg / kg to establish the model rats with autism spectrum disorder. The control group was injected with the same dose of saline. HE staining, immunohistochemistry and image analysis were used to observe the expressions of CaMKⅡ and ERK in the brain of rats at 1, 7, 14 and 28 days after birth. Results HE staining: The number of neurons on the 1st and 7th day after birth was less in the model group than in the control group after 14 days of birth, and was significantly higher on the 28th day after birth. Immunohistochemistry: The expressions of CaMKⅡ and ERK in both groups were significantly increased (P <0.001) between the 1st and 14th day after birth, and the expression tended to be stable after 28 days (P> 0.05). Compared with the control group, (P <0.001). The expression of CaMKⅡ and ERK at 1d and 7d after birth were significantly increased (P <0.001), and reached the highest at 14d after birth (P <0.001). After 28d, the expression of CaMKⅡ and ERK increased Stable (P> 0.05). Conclusions The expression of CaMKⅡ and ERK in the cerebral cortex of autism spectrum disorders is increased, especially in the early postnatal period.