肾上腺髓质素及其受体系统在维生素D(3)加尼古丁诱导的大鼠心血管钙化中的作用。
The role of adrenomedullin and its receptor system in cardiovascular calcification of rat induced by Vitamin D(3) plus nicotine.
作者信息
Pan C S, Qi Y F, Wu S Y, Jiang W, Li G Z, Tang C S
机构信息
Institute of Cardiovascular Diseases, Peking University First Hospital, Beijing 100034, China.
出版信息
Peptides. 2004 Apr;25(4):601-8. doi: 10.1016/j.peptides.2004.02.020.
Adrenomedullin (ADM) is a potent vasodilatory peptide which regulates blood pressure, cell growth and bone formation. Our work was aimed to explore the production of ADM, changes and pathophysiological significance of ADM mRNA and ADM receptor components--calcitonin receptor like receptor (CRLR) and receptor activity modifying proteins (RAMPs) mRNA in calcified myocardium and aorta of rats induced by Vitamin D3 plus nicotine. Contents of ADM in plasma, myocardium and aorta were measured by radioimmunoassay (RIA). The amount of ADM, CRLR and RAMPs mRNA was determined by semi-quantitative RT-PCR. The calcium content and alkaline phosphatase activity in myocardium and aorta of rats were measured. The results showed that the contents of calcium in calcified myocardium and aorta were increased by 3.5- and 6-fold (all P < 0.01), respectively, and alkaline phosphatases activity in calcified myocardium and aorta were increased by 66.5 and 82.7% (all P < 0.01 ), respectively, compared with control. Contents of ADM in plasma, myocardium and aorta were increased by 58% (P < 0.01), 14.3% (P < 0.01) and 27.8% P < 0.05). Furthermore, it was found that the amount of ADM, CRLR and RAMP2 mRNA in calcified myocardium was elevated by 90.6, 157.5 and 119.6% (all P < 0.01), RAMP3 mRNA was decreased by 14.1% (P < 0.01), respectively, compared with control. The amount of ADM, CRLR, RAMP2 and RAMP3 mRNA in calcified aorta was elevated by 37.7% (P < 0.01), 41.4% (P < 0.01), 60.1% (P < 0.05) and 13% P < 0.01), respectively, compared with control. The elevated level of CRLR and RAMP2 mRNA were in positive correlation with that of ADM mRNA (r = 0.992 and 0.882, respectively, P < 0.01) in calcified myocardium. The elevated level of CRLR and RAMP3 mRNA were also in positive correlation with that of ADM mRNA (r = 0.727, P < 0.05 and 0.816, P < 0.01, respectively) in calcified aorta. These results demonstrated that calcified myocardium and aorta generated an increased amount of ADM, up-regulated gene expressions of ADM, CRLR and RAMP2 mRNA. While the alteration of RAMP3 mRNA in calcified myocardium and aorta was different. These suggested that ADM and its receptor system might involve in the regulation of calcification in heart and aorta.
肾上腺髓质素（ADM）是一种强效血管舒张肽，可调节血压、细胞生长和骨形成。我们的研究旨在探讨维生素D3加尼古丁诱导的大鼠钙化心肌和主动脉中ADM的产生、ADM mRNA以及ADM受体成分——降钙素受体样受体（CRLR）和受体活性修饰蛋白（RAMPs）mRNA的变化及其病理生理意义。采用放射免疫分析法（RIA）测定血浆、心肌和主动脉中ADM的含量。通过半定量逆转录聚合酶链反应（RT-PCR）测定ADM、CRLR和RAMPs mRNA的量。测定大鼠心肌和主动脉中的钙含量及碱性磷酸酶活性。结果显示，与对照组相比，钙化心肌和主动脉中的钙含量分别增加了3.5倍和6倍（均P<0.01），钙化心肌和主动脉中的碱性磷酸酶活性分别增加了66.5%和82.7%（均P<0.01）。血浆、心肌和主动脉中ADM的含量分别增加了58%（P<0.01）、14.3%（P<0.01）和27.8%（P<0.05）。此外，发现与对照组相比，钙化心肌中ADM、CRLR和RAMP2 mRNA的量分别升高了90.6%、157.5%和119.6%（均P<0.01），RAMP3 mRNA减少了14.1%（P<0.01）。与对照组相比，钙化主动脉中ADM、CRLR、RAMP2和RAMP3 mRNA的量分别升高了37.7%（P<0.01）、41.4%（P<0.01）、60.1%（P<0.05）和13%（P<0.01）。钙化心肌中CRLR和RAMP2 mRNA的升高水平与ADM mRNA的升高水平呈正相关（r分别为0.992和0.882，P<0.01）。钙化主动脉中CRLR和RAMP3 mRNA的升高水平也与ADM mRNA的升高水平呈正相关（r分别为0.727，P<0.05和0.816，P<0.01）。这些结果表明，钙化心肌和主动脉产生了更多的ADM，上调了ADM、CRLR和RAMP2 mRNA的基因表达。而钙化心肌和主动脉中RAMP3 mRNA的变化不同。这些提示ADM及其受体系统可能参与心脏和主动脉钙化的调节。
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