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Intermedin/adrenomedullin 2及其受体在慢性低氧性肺动脉高压大鼠右心室的表达变化

龚永生, 范小芳, 吴小脉, 胡良冈, 唐朝枢, 庞永政, 齐永芬

温州医学院肺心病研究室,机能实验教学中心.浙江,温州 325035；北京大学第一医院心血管研究所.北京 100034

摘要

该研究探讨了新发现的小分子生物活性肽intermedin／adrenomedullin 2(IMD／ADM2)及其受体在慢性低氧性肺动脉高压大鼠右心室中的变化和可能作用。用放射免疫分析法测定正常对照组和常压低氧4周组Sprague--Dawley大鼠血浆、右心室匀浆IMD／ADM2和肾上腺髓质素(adrenomednllin,ADM)蛋白水平;逆转录--多聚酶链反应法测定右心室IMD／ADM2、ADM及受体:降钙素受体样受体(calcitonin receptor--like receptor,CRLR)、受体活性修饰蛋白1,2,3(receptor activity modifying protein 1,2,3,RAMP1,RAMP2,RAMP3)mRNA表达。结果显示:低氧组平均肺动脉压、右心室与左心室加室间隔重量比[RV／(LV+S)]显著高于对照组(均{sl P}<0.01);低氧组血浆和右心室组织匀浆ADM水平比对照组分别高1.26倍和1.68倍({sl P}<0.01),IMD／ADM2水平则较对照组分别高0.90倍和1.19倍({sl P}<0.01);与对照组相比,低氧组右心室IMD／ADM2、ADM mRNA表达均上调({sl P}<0.01),RAMP2 mRNA表达增强({sl P}<0.05),而两组间CRLR、RAMP1、RAMP3 mRNA的表达水平无显著性差异。结果表明,慢性低氧性肺动脉高压大鼠IMD/ADM2表达水平升高。

关键词： 肾上腺髓质素; intermedin; 受体; 低氧; 高血压; 肺性

Changes of intermedin/adrenomedullin 2 and its receptors in the right ventricle of rats with chronic hypoxic pulmonary hypertension

Gong Yongsheng, Fan Xiaofang, Wu Xiaomai, Hu Lianggang, Tang Chaoshu, Pang Yongzheng, Qi Yongfen

Institute of Cor Pulmonale and Teaching Centre of Functional Experiment,Wenzhou Medical College.Wenzhou 325035,Zhejiang；China

Abstract

The purpose of the present study was to explore the expression changes of intermedin/adrenomedullin 2 (IMD/ADM2), a novel small molecular bioactive peptide, and its receptors, calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMP1, RAMP2, RAMP3) in the right ventricle of rats with chronic hypoxia-induced pulmonary hypertension. Twenty male Sprague-Dawley rats were randomly divided into 4-week hypoxia group and normal control group (each n=10). The rats in hypoxia group were placed in an isobaric hypoxic chamber, in which O_(2) content was maintained at 9%--11% by delivering N_(2), and CO_(2) content was maintained at <3% for 4 weeks (8 h/d, 6 d/week). The rats in the control group were housed in room air. The protein levels of IMD/ADM2 and adrenomedullin (ADM) in blood plasma and right ventricular tissue were measured by radioimmunoassay. The mRNA expressions of IMD/ADM2, ADM and their receptors CRLR, RAMP1, RAMP2, RAMP3 in right ventricular tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the ratio of right ventricle weight to left ventricle plus septum weight［RV/(LV+S)］ and mean pulmonary arterial pressure (mPAP) were higher in hypoxia group than those in the control group (all P<0.01), suggesting that the successful rat model of pulmonary hypertension was established. However, the mean carotid arterial pressure (mCAP) between the two groups had no significant difference. Compared with that in the control group, ADM contents in plasma and right ventricular tissue in hypoxia group increased by 1.26 and 1.68 folds (all P<0.01), respectively. Likewise, the IMD/ADM2 contents in plasma and right ventricular tissue in hypoxia group increased by 0.90 and 1.19 folds (P<0.01), respectively, compared with that in the control group. The data of RT-PCR showed that mRNA levels of ADM, IMD/ADM2 and RAMP2 in hypoxia group increased by 155.1%(P<0.01), 80.9% (P<0.01) and 52.9% (P<0.05), respectively. compared with those in the control group. There were no significant differences in the mRNA expressions of CRLR, RAMP1 and RAMP3 between the two groups (all P>0.05). Taken together, the results show that the levels of IMD/ADM2 increase in the rats with chronic hypoxic-induced pulmonary hypertension.

Key words: Adrenomedullin;intermedin;Receptor;Hypoxia;Hypertension;pulmonary

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引用本文：

龚永生, 范小芳, 吴小脉, 胡良冈, 唐朝枢, 庞永政, 齐永芬. Intermedin/adrenomedullin 2及其受体在慢性低氧性肺动脉高压大鼠右心室的表达变化[J]. 生理学报 2007; 59 (2): 210-214.

Gong Yongsheng, Fan Xiaofang, Wu Xiaomai, Hu Lianggang, Tang Chaoshu, Pang Yongzheng, Qi Yongfen. Changes of intermedin/adrenomedullin 2 and its receptors in the right ventricle of rats with chronic hypoxic pulmonary hypertension. Acta Physiol Sin 2007; 59 (2): 210-214 (in Chinese with English abstract).