海马NMDA受体调节严重烫伤应激后HPA轴兴奋性的相关机制研究  

Mechanisms of hippocampal NMDA receptor in regulating over-excitation of HPA axis in rats with scalding-induced stress

作　　者：叶建宁[1] 陆建华[2] 熊加祥[3] 

机构地区：[1]第三军医大学新桥医院神经内科,重庆400037 [2]广州军区总医院麻醉科,广州510010 [3]第三军医大学生理教研室,重庆400038

出　　处：《中华神经医学杂志》2006年第10期982-985,共4页Chinese Journal of Neuromedicine

摘　　要：目的探寻海马N-甲基-D-天冬氨酸(NMDA)受体调节严重创伤应激后HPA轴过度兴奋的可能机制。方法以30%总体表面积(TBSA)Ⅲ度烫伤应激作为严重创伤应激模型,先通过地塞米松抑制试验检测严重烫伤应激后糖皮质激素(GC)负反馈功能的变化,再利用RT-PCR技术检测烫伤应激后海马糖皮质激素受体(GR)mRNA水平(其水平与负反馈功能密切相关)的变化特点,并观察烫伤应激前腹腔注射NMDA受体拮抗剂MK-801对烫伤应激后2hGRmRNA水平的影响。结果30%TBSAⅢ度烫伤应激后地塞米松抑制试验阴性,GC负反馈功能下降;烫伤应激后0.5、2、8、24、48h海马GRmRNA水平皆明显降低,尤以伤后2h最明显;与烫伤应激组相比,MK-8013mg/kg组GRmRNA水平显著上升,MK-8016mg/kg组海马GRmRNA水平进一步上升,盐水组GRmRNA水平无明显变化。结论海马NMDA受体调节严重烫伤应激后HPA轴的亢进是通过下调海马GR从而影响了GC在海马水平的负反馈引起的。Objective To investigate the mechanism by which hippocampal NMDA receptor regulates the over-excitation of HPA axis following the stress caused by high temperature scalding. Methods Adult male Wistar rats were inflicted with 30% TBSA Ⅲ degree scalding, which was applied as severe trauma stress models. Negative feedback response of glucocorticoid （GC） to severe scalding was detected with dexamethasone suppression test. GC receptor （GR） mRNA levels in rat hippocampus of each group were detected with RT-PCR technique. What＇s more, the effect of the intraperitoneal injection of NMDA receptor antagonist （MK-801） before scalding on the GR mRNA level was observed 2 h after scalding-induced stress. Results Serum cortisol concentration did not change obviously in the model rats pretreated with the intraperitoneal injection of dexamethasone （artificial GC） as compared with the rats non-pretreated with the drug. Hippocampal GR mRNA level was markedly decreased at 0.5, 2, 8, 24,48 h after scalding. The decrease of GR mRNA levels which was most obvious at 2 h after scalding was significantly inhibited by administering 3 mg/kg MK-801, prior to exposure to burn, and more significantly inhibited by administering 6 mg/kg MK-801. Conclusion The roles of hippocampal NMDA receptor in HPA axis over-activation after scalding is partially via inhibiting GR gene expression which is responsible for disrupted negative feedback to severe scalding.

关 键 词：海马 烫伤 应激 NMDA受体 HPA轴 糖皮质激素受体 

分 类 号：R644[医药卫生—外科学]