急性高台应激对大鼠神经内分泌激素、相关受体及脑神经递质的影响

目的 高台应激是一种不可逃避应激,是研究应激对机体神经生理病理变化的重要模型.本研究对急性高台应激后神经内分泌激素、受体表达、脑神经递质变化以及地西泮的干预作用进行探讨.方法 大鼠随机分为空白对照组、应激+地西泮(DAP)组与应激+溶剂组.后两组于应激前30 min分别腹腔注射地西泮2 mg/kg与等量生理盐水.采用酶联免疫法测量应激后各组的血浆促肾上腺皮质激素(ACTH)、血清皮质酮(CORT)水平;采用实时定量PCR测量下丘脑促肾上腺皮质激素分泌激素(CRH)mRNA、海马糖皮质激素受体(GR)mRNA、盐皮质激素受体(MR) mRNA、5-羟色胺1a受体(5-HT1aR)mRNA水平;采用高效液相色谱电化学法测量大脑皮层匀浆液中去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5-HIAA)水平.结果 与空白组相比,应激+溶剂组大鼠血浆ACTH、血清CORT以及海马5-HT1aR mRNA水平升高(P均＜0.05),此变化可由DAP逆转(P均＜0.05).此外,DAP还可降低应激后的下丘脑CRH mRNA,海马GR mRNA以及MR mRNA水平(P均＜0.05).然而大脑皮层匀浆液中NE、DA、5-HT、5-HIAA在应激后无变化.结论 急性高台应激可引起大鼠相关神经内分泌激素与受体表达变化,且该效应可被DAP逆转.

The impact of exposure to acute elevated platform on the expression of neuroendocrine hormones,receptors, and neurotransmitters of rats

Objects Elevated platform stress is an important model to study the acute stress-induced neurophysiologic changes of organisms.In this study,we investigated the effect of the elevated platform stress and/or diazepam (DAP) on the expression of neuroendocrine hormones,receptors,and neurotransmitters in rats.Methods Rats were randomly divided into three groups:na(i)ve group,stress + DAP group,and stress + vehicle group.The last two groups were given DAP (2 mg/kg in vehicle,i.p.) and vehicle (i.p.) 30 min ahead of stress,respectively.The levels of plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT) were determined by enzyme-linked immuno sorbent assay (ELISA).The mRNA level of hypothalamus corticotropin releasing hormone (CRH),hippocampus glucocorticoid receptors (GR),mineralocorticoid receptor (MR),and 5-hydroxytryptophan receptor (5-HT1 aR) were determined by quantitative real-time PCR.The amount of norepinephrine (NE),dopamine (DA),5-hydroxytryptophan (5-HT),and 5-hydroxyindoleacetic acid (5-HIAA) were determined by HPLC-Electrochemical Detection.Results Compared with the na(i)ve group,levels of plasma ACTH,serum CORT,and hippocampus 5-HT1aR mRNA in the last two groups increased after exposure to the stress (all p ＜ 0.05).Such increases could be reversed by DAP (all P ＜ 0.05).In additional,DAP could down-regulate the mRNA level of hypothalamus CRH,hippocampus GR and MR (all P ＜ 0.05).Meanwhile,elevated stress and DAP have no significant effect on the NE,DA,5-HT,and 5-HIAA level.Conclusion The acute elevated platform stress induces higher levels of neuroendocrine hormones and receptors in rats.This effect can be reversed by DAP.