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应激性高血压大鼠脑干及下丘脑--垂体--肾上腺轴中肾上腺髓质素及其受体mRNA表达的改变

李霞, 李良, 沈霖霖, 钱源, 曹银祥, 朱大年

复旦大学上海医学院生理与病理生理教研室.上海 200032

摘要

采用逆转录--聚合酶链式反应检测了慢性足底电击结合噪声应激致高血压大鼠下丘脑、延髓、中脑、垂体和肾上腺等组织中编码肾上腺髓质素的肾上腺髓质素前肽原(preproadrenomedullin,ppADM)基因以及ADM的特异性受体组件降钙素受体样受体(calcitonin-receptor-like receptor,CRLR)和受体活性调节蛋白2和3(receptor--activty--modifying proteins,RAMP2和RAMP3)表达的变化。作者观察到:与对照组相比,以3-磷酸甘油醛脱氢酶作为内参照,15 d足底电击结合噪声应激引起下丘脑、垂体和肾上腺中ppADM mRNA表达上调,而在延髓和中脑表达明显下调({sl P}＜0.01或{sl P}＜0.05);CRLR基因表达量正常时在下丘脑相对较高,应激15 d后CRLR表达在延髓、中脑和下丘脑下调({sl P}＜0.01或{sl P}＜0.05),而在垂体和肾上腺的表达无明显变化;应激后RAMP2基因在延髓和下丘脑表达上调,而在肾上腺表达显著下调({sl P}＜0.01),其他部位无明显变化;RAMP3基因在对照组大鼠的中脑和下丘脑表达较高,在应激性高血压大鼠的下丘脑和垂体表达上调({sl P}＜0.01或{sl P}＜0.05),而在中脑和肾上腺表达下调({sl P}＜0.05),在延髓中的表达变化无统计学差异。上述结果提示:慢性足底电击结合噪声应激引起明显的中枢和下丘脑--垂体--肾上腺轴ADM及其受体组件CRLR/RAMP2或CRLR/RAMP3基因的表达变化。但慢性应激后中枢源性ADM及其受体的表达变化对应激和血压的调节以及在应激致高血压中的确切作用及机制尚待进一步研究。

关键词： 肾上腺髓质素; 受体; 脑干; 下丘脑-垂体-肾上腺轴; 逆转录-聚合酶链式反应; 应激; 高血压大鼠

Changes of adrenomedullin and its receptor components mRNAs expression in the brain stem and hypothalamus--pituitary--adrenal axis of stress--induced hypertensive rats

Li Xia, Li Liang, Shen Linlin, Qian Yuan, Cao Yinxiang, Zhu Danian

Department of Physiology and Pathophysiology,Shanghai Medical College of Fudan University.Shanghai 200032

Abstract

In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the changes in mRNAs levels of preproadrenomedullin (ppADM) gene encoding adrenomedullin (ADM) and the essential receptor components of ADM, calcitonin receptor-like receptor (CRLR), and the receptor activity modifying protein 2 and 3 (RAMP2 and RAMP3) in the medulla oblongata,hypothalamus, midbrain, pituitary gland and adrenal gland of the stress-induced hypertensive rats. It was shown that chronic footshock and noise stress for 15 consecutive days induced a significant increase in systolic blood pressure (SBP) and unique changes in ppADM and its receptor components mRNAs in all areas studied. As compared with the control group, the level of ppADM mRNA,normalized against a glyceraldehydes-3-phosphate dehydrogenase (GAPDH) control, was up-regulated in the hypothalamus-pituitary-adrenal (HPA) axis, but down-regulated in the medulla oblongata and midbrain (P＜0.01 and P＜0.05, respectively). The relative amount of CRLR mRNA was higher in the hypothalamus than that in other areas. The level of CRLR mRNA expression was significantly increased in the medulla oblongata of the stress group (P＜0.01), but decreased in the midbrain (P＜0.01) as well as hypothalamus(P＜0.05), as compared with that of the control group. Chronic stress for 15 consecutive days produced an increase in the level of RAMP2 mRNA expression in the medulla oblongata (P＜0.01) and a decrease in the adrenal gland (P＜0.01), as compared with the control. No significant stress-related changes in RAMP2 mRNA were observed in the midbrain, hypothalamus and pituitary gland.The amount of RAMP3 mRNA was relatively higher in the midbrain and hypothalamus than that in the medulla oblongata, adrenal gland and adrenal gland. Stress-induced hypertensive rats exhibited an increased RAMP3 mRNA expression in the hypothalamus and pituitary gland (P＜0.01 and P＜0.05, respectively) and a decrease in the adrenal gland and midbrain (P＜0.05). No significant stressrelated change in RAMP3 mRAN was observed in the medulla oblongata. Taken together, our results indicate that the significant changes in ppADM and its receptor components mRNAs expression in the HPA axis and autonomic centers may be related to the development of the stress-induced hypertension. Nevertheless, the pathophysiological significance of brain-derived ADM and its receptors in stress and blood pressure regulation and their roles in stress-induced hypertension still await further investigation.

Key words: adrenomedullin;Receptor;brain stem;HPA axis;RT-PCR;Stress;hypertensive rats

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引用本文：

李霞, 李良, 沈霖霖, 钱源, 曹银祥, 朱大年. 应激性高血压大鼠脑干及下丘脑--垂体--肾上腺轴中肾上腺髓质素及其受体mRNA表达的改变[J]. 生理学报 2004; 56 (6): .

Li Xia, Li Liang, Shen Linlin, Qian Yuan, Cao Yinxiang, Zhu Danian. Changes of adrenomedullin and its receptor components mRNAs expression in the brain stem and hypothalamus--pituitary--adrenal axis of stress--induced hypertensive rats. Acta Physiol Sin 2004; 56 (6): (in Chinese with English abstract).