钙化大鼠心血管组织肾上腺髓质素及其受体系统的变化

Alterations of adrenomedullin and its receptor system in calcified myocardium and aorta of rats

目的 :探讨钙化大鼠心血管组织肾上腺髓质素 (adrenomedullin ,ADM)生成和ADM及其受体系统———降钙素受体样受体 (calcitoninreceptor likereceptor,CRLR)与受体活性修饰蛋白 (receptoractivitymodifyingprotein ,RAMPs)基因表达的改变及其病理意义。方法 :放射免疫法测定血浆、心肌和血管组织ADM含量 ;半定量RT PCR方法测定心肌和血管ADM、降钙素受体样受体 (CRLR)和RAMP2 / 3mRNA水平。结果 :与对照组大鼠比较 ,钙化大鼠心肌和主动脉钙含量分别高 342 %和 6 0 6 % (P <0 .0 1) ;心肌和主动脉碱性磷酸酶活性分别高 6 6 .5 % (P <0 .0 5 )和 82 .7% (P <0 .0 1)。钙化组大鼠血浆、心肌和血管ADM含量分别较对照组高 5 8% (P <0 .0 1) ,14 .3% (P <0 .0 1)和 2 7.8% (P <0 .0 5 ) ;心肌ADM、CRLR和RAMP2的mRNA水平较对照组分别高 90 .6 % ,15 7.5 %和 119.6 % (均P <0 .0 1) ,而RAMP3mRNA水平较对照组低 14 .1% (P <0 .0 1) ;血管组织ADM、CRLR、RAMP2和RAMP3的mRNA水平较对照组分别高 37.7% (P <0 .0 1) ,4 1.4 % (P <0 .0 1) ,6 0 .1% (P <0 .0 5 )和 13% (P <0 .0 1)。心血管组织中ADM与其受体系统mRNA变化水平有一定的相关性。结论 :钙化大鼠心血管组织ADM生成增加 ,ADM、CRLR和RAMP2 /

Objective: To explore the production of ADM, changes and significance of adrenomedullin (ADM) mRNA and ADM receptor system-calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) mRNA in calcified myocardium and aorta of rats. Methods: Contents of ADM in plasma, myocardium and vessel were measured by radioimmunoassay (RIA). The amount of ADM, CRLR and RAMPs mRNA was determined by semi-quantitative RT-PCR. Results: The contents of calcium in calcified myocardium and aorta were increased by 342 % and 606 % (all P<0.01), respectively, and alkaline phosphatase activities in calcified myocardium and vessel were increased by 66.5 % and 82.7 % (all P<0.01), respectively, compared with the 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 levels of ADM, CRLR and RAMP2 mRNA in calcified myocardium were elevated by 90.6 %,157.5 % and 119.6 %(all P<0.01), respectively, but RAMP3 mRNA was decreased by 14.1 %(P<0.01). The levels of ADM, CRLR, RAMP2 and RAMP3 mRNA in calcified aorta were 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 the control. The elevated levels of CRLR, RAMP2 or RAMP3 mRNA were positively correlated with up-regulations of ADM mRNA in calcified myocardium and aorta. Conclusion: Calcified myocardium and aorta may generate an increased amount of ADM, different alterations of gene expressions of ADM and its receptor system. These results suggest that ADM and its receptor system might participate in the regulation of calcification in heart and vessel.