SP600125对新生期母婴分离后成年大鼠行为改变的保护作用及机制.docVIP

SP600125对新生期母婴分离后成年大鼠行为改变的保护作用及机制 　　摘要：目的 探讨JNK特异性抑制剂SP600125对新生期母婴分离后成年大鼠行为改变的保护作用及机制。方法 复制新生期母婴分离动物模型。随机分三组：对照组、母婴分离组与母婴分离+SP600125干预组。在2个月时，用三桶互通脑功能仪测定成年后大鼠行为的改变，并采用免疫组化法检测caspase-3在成年大鼠脑组织海马中的表达。结果 SP600125组成年后大鼠自发活动的总路程与平均速度较母婴分离组有所增加，但尚未恢复到对照组水平；海马组织caspase-3表达量母婴分离组较对照组明显增加（P0.05），SP600125组较母婴分离组明显减少（P0.05），但未恢复至对照组水平。结论 SP600125可能通过抑制JNK信号通路，降低caspase-3的表达，从而改善新生期母婴分离后成年大鼠的认知障碍。 　　关键词：新生期母婴分离；C-Jun蛋白氨基末端激酶；半胱氨酸天冬氨酸蛋白酶3 　　Protective Effects and Mechanism of SP600125 on the Behavior Change in Adult Rats after Neonatal Maternal Separation 　　DANG Jia-wen， DONG Wen-bin， GUO Lin， KANG Lan 　　（Luzhou Medical College Affiliated Hospital Neonatology Department， Luzhou Sichuan 646000， China） 　　Abstract：Objective To investigate the protective effect and mechanism of SP600125 on the behavior change in adult rats after neonatal maternal separation. Methods Neonatal rats were divided into three groups：control group，neonatal maternal separation group，neonatal maternal separation group+SP600125 group. On the two months old，by three links exchange apparatus of brain function the changes of adult rat behavior were tested； the expression of caspase-3 in hippocampus were detected by immunohistochemical method. Results Compared with neonatal maternal separation group，both the total distance and average speed of locomotor activity were increased in SP600125 group，but not to the same as that of control group. The expression of hippocampus caspase-3 in neonatal maternal separation group increased compared with control group （P0.05） and that decreased in SP600125 group compared with neonatal maternal separation group （P0.05），but not to the same as that of control group. Conclusion SP600125 can suppress JNK signal pathway， reduce the expression of caspase-3，so that it improves the cognitive impairment. 　　Key words：Neonatal mother separation； JNK； Caspase-3 　　新生儿期母婴分离是人类生命早期最为常见的应激事件。本课题组前期研究发现，新生期母婴分离后可引起成年大鼠自发活动减少，导致新生鼠成年后认知障碍，学习记忆能力减退[1]。而海马组织是学习和记忆的关键部位。为此，本研究在前期建立新生期母婴分离模型