JNK1/2通路蛋白及凋亡基因Caspase-3在高温致神经管畸形作用中的表达

Expressions of the JNK1/2 pathway and Caspase-3 in the development of neural tube defects caused by Hyperthermia

目的探讨高温致畸MAPKs中JNK1/2通路蛋白及凋亡基因Caspase-3的表达作用及其机理。方法孕鼠于受精第8天置42℃水浴,持续20min后,分别于2、8、16、24、48、72h经麻醉处死剖腹取胎,并分为高温组(2～72h,42℃)和对照组(2～72h,37℃)。采用Westernblot技术检测JNK1/2、P-JNK1/2及Caspase-3的表达量。结果高温组JNK1/2的表达量与对照组无明显差异,各组内不同时间的表达量无明显变化;P-JNK1/2在对照组中不表达,高温组8～48h时的表达量均高于相应的对照组(P<0.05),于16h时表达增加最为显著;Caspase-3在对照组中无表达,在高温组8～48h时表达增加(P<0.05),于8h时增加最为显著。结论高温刺激能促使JNK1/2发生磷酸化和凋亡基因Caspase-3的活化,这可能是高温致胚胎先天性畸形的原因之一。

Objective To study expressions and roles of the JNK1/2 pathway of MAPKs and Caspase-3 in the development of neural tube defects caused by hyperthermia.Methods Pregnant golden hamsters in the hyperthermia group were immersed in hot water（42 ℃）for 20 min on GD8.After treatment of 2,8,16,24,48 and 72 h,the hamsters were terminated after anesthesia and the embryos were removed from the fetal membrane,and divided into the hyperthermia group（2-72 h,42 ℃）and the control group（2-72 h,37 ℃）.Expressions of the JNK1/2 pathway and P-JNK1/2 and Caspase-3 were measured by Western blot.Results Expression of JNK1/2 had no significant changes in the two groups.However,P-JNK1/2 activity increased in the hyperthermia group at 8-48 h and the amount increased significantly compared with the control group（P〈0.05）,and the peak appeared at 16 h.Caspase-3 activity had no significant changes in the control group but increased in the hyperthermia group,and the amount of Caspase-3 increased compared with the control group at 8-48 h（P〈0.05）,and the peak appeared at 8 h.Conclusion The P-JNK1/2 pathway and Caspase-3 were stimulated by hyperthermia,which maybe one of the pathway that induces the development of neural tube defects.