皮质激素受体在抑郁大鼠海马GIRK_(1-4) mRNA调控中的作用  

Glucocorticoid receptor in regulation of GIRK_(1-4) mRNA expression in hippocampus subfields in chronic stress-induced depression rat models

作　　者：刘世建[1] 马国昭 王雪琦[1] 高霄飞[1] 徐荷 何成[1] 路长林[1] 

机构地区：[1]第二军医大学基础医学部神经生物学教研室,上海200433 [2]卫生勤务学系流行病学教研室,上海200433

出　　处：《第二军医大学学报》2004年第10期1058-1061,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金重点项目 ( 3 993 0 0 80 )

摘　　要：目的 :侧脑室给予螺内酯和 (或 )米非司酮 ,观察大鼠海马 G蛋白偶联内向整流钾通道 1- 4 (GIRK1 - 4) m RNA的表达 ,初步探讨皮质激素受体在调控 GIRK m RNA中的作用。方法 :雄性 SD大鼠 ,随机分为 9组 (每组 5只 ) :对照组 (CON) ,生理盐水组 (NS) ,螺内酯组 (SPI) ,米非司酮组 (MIF) ,SPI+MIF组 ,抑郁 (DEP) +NS组 ,DEP+SPI组 ,DEP+MIF组 ,DEP+SPI+MIF组。用地高辛 (DIG)标记的 GIRK1 - 4c RNA探针进行原位杂交 ;切片贴于涂有铬矾明胶的载玻片上 ,37℃烘箱中过夜。常规脱水 ,透明 ,中性树胶封片。利用 L eica图像分析系统测定海马各区 GIRK1 - 4m RNA杂交阳性信号的平均灰度。使用SPSS进行统计学分析。 结果 :与 CON组相比 ,DEP+NS组海马 CA1- 3区和齿状回 GIRK1 - 4m RNA表达均明显下降 ;与DEP+NS组相比 ,DEP+SPI组和 DEP+SPI+MIF组海马各区 GIRK1 - 4m RNA表达均明显升高 ,DEP+MIF组变化不显著 ,SPI组、MIF组和 SPI+MIF组与 NS组相比 ,GIRK1 - 4m RNA表达无明显差异 ,表明 SPI和 MIF本身对正常大鼠 GIRK表达的影响不明显。 结论 :糖皮质激素受体通过与 GIRK1 中的糖皮质激素受体反应元件结合 ,使 GIRKs m RNA在海马的表达增加 ,皮质酮通过海马的 5 - HT1 A受体增加 GIRKs通道的通透性 。Objective:To observe the G-protein coupled inwardly rectifying potassium channels (GIRK) mRNA expression in hippocampus in chronic stress-induced depression rat models after intracerebroventricular injection of glucocorticoid receptor antagonist and/or mineralocorticoid receptor antagonist,providing information for the mechanism of glucocorticoid receptor regulating GIRK mRNA.Methods: Male Sprague-Dawley rats,weighing 160-180 g,were divided into 9 groups (n=5): control(CON),depression(DEP)+saline(NS),DEP+spironolactone(SPI),DEP+mifepristone(MIF),DEP+SPI+MIF,NS,SPI,MIF,SPI+MIF group.In situ hybridization was carried out with digoxin labeled GIRK 1-4 cRNA probe.The sections were mounted onto gelatin-coated slides and air dried before being mounted in glycerol phosphate.The GIRKs mRNA expression were measured by positive signal average gray using Leica imagination analysis system.Statistical analysis was carried out by SPSS.Results: The intensity of GIRK 1-4 mRNA hybridization positive signal in DEP+NS group was significantly decreased in the CA1-3 and dentate gyrus of hippocampus compared with that in CON group (P<0.05);GIRK 1-4 mRNA level of DEP+SPI group was higher than DEP+NS group (P<0.05);GIRK 1-4 mRNA signal intensity of DEP+MIF group was not significantly different compared to DEP+NS group;GIRK 1-4 mRNA expression of DEP+SPI+MIF was higher than that of DEP+NS group (P<0.05).Conclusion: Glucocorticoid receptor binding to glucocorticoid receptor element of GIRK 1 increases the expression of GIRKs mRNA and corticosterone enhances the GIRKs permeability through 5-HT 1A receptor.The above 2 factors regulate GIRK 1-4 mRNA expression in hippocampus in chronic stress-induced depression model of rats.

关 键 词：糖皮质激素受体 G蛋白偶联内向整流型钾通道 海马 应激型抑郁症 

分 类 号：R749.41[医药卫生—神经病学与精神病学]