Fan Xiao-fang, Huang Ping, Gong Yong-sheng, Wu Xiao-mai, Hu Liang-gang, Tian Li-xian, Tang Chao-shu, Pang Yong-zheng
Institute of Cor Pulmonale, Wenzhou Medical College, Wenzhou 325035, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2007 Nov;23(4):467-71.
To investigate the changes and probable roles of adrenomedullin2/intermedin (AIDM2/IMD), a novel micromolecular bioactive peptide, in the lungs of rats with chronic hypoxic pulmonary hypertension.
Twenty male SD rats were randomly divided into normal control group (NC) and normobaric hypoxia group (4H). The protein levels of ADM and ADM2/IMD) in the plasma and lung were measured by radioimmunoassay and immunohistochemistry. The mRNA expressions of ADM, ADM2/IMD and their receptors C (RLR, RAMP1, RAMP2 and RAMP3 in the lung tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR).
(1) The rat model of chronic pulmonary hypertension was confirmed by the increased mean pulmonary arterial pressure (mPAP) and weight ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] in 4H group compared to NC group. (2) The concentrations of ADM in the plasma and lung homogenate of 4H group were 2.3 and 3.2 folds of NC group, respectively (all P < 0.01). The levels of ADM2/IMD were higher 89.6% and 45.0% in the plasma and lung homogenate of 4H group than those of NC group (respectively, P < 0.01, P < 0.05). (3) The mRNA expressions of ADM2/IMD and ADM in the lung of 4H group were up-regulated (respectively, P < 0.01, P < 0.05 vs. NC group). The expressions of CRLR and RAMP1 mRNAs were down-regulated (all P < 0.01 vs. NC group), while the levels of RAMP2 and RAMP3 mRNAs were no significant difference between the two groups. (4) The strong ADM2/IMD immunostaining was detected in the endothelial and adventitial cells of the rat pulmonary arteriole.
ADM2/IMD, like its paralog ADM, might be closely related to the chronic hypoxic pulmonary hypertension in rats. The disorders of the gene expression and/or the synthesis and metabolism of ADM2/IMD and its receptor CRLR/RAMP1 possibly take part in the pathogenesis of chronic hypoxic pulmonary hypertension in rats.
研究一种新型小分子生物活性肽肾上腺髓质素2/中间介质（ADM2/IMD）在慢性缺氧性肺动脉高压大鼠肺组织中的变化及可能作用。
将20只雄性SD大鼠随机分为正常对照组（NC）和常压缺氧组（4H）。采用放射免疫分析法和免疫组织化学法检测血浆和肺组织中ADM及ADM2/IMD的蛋白水平。采用逆转录-聚合酶链反应（RT-PCR）检测肺组织中ADM、ADM2/IMD及其受体CRLR、RAMP1、RAMP2和RAMP3的mRNA表达。
（1）与NC组相比，4H组大鼠平均肺动脉压（mPAP）及右心室与左心室加室间隔重量比[RV/（LV+S）]升高，证实慢性肺动脉高压大鼠模型建立。（2）4H组血浆和肺匀浆中ADM浓度分别为NC组的2.3倍和3.2倍（均P<;0.01）。4H组血浆和肺匀浆中ADM2/IMD水平分别比NC组高89.6%和45.0%（分别为P<;0.01，P<;0.05）。（3）4H组肺组织中ADM2/IMD和ADM的mRNA表达上调（与NC组相比，分别为P<;0.01，P<;0.05）。CRLR和RAMP1 mRNA表达下调（与NC组相比，均P<;0.01），而RAMP2和RAMP3 mRNA水平在两组间无显著差异。（4）在大鼠肺小动脉内皮细胞和外膜细胞中检测到强ADM2/IMD免疫染色。
ADM2/IMD与其同源物ADM一样，可能与大鼠慢性缺氧性肺动脉高压密切相关。ADM2/IMD及其受体CRLR/RAMP1的基因表达和/或合成代谢紊乱可能参与大鼠慢性缺氧性肺动脉高压的发病机制。
