中介素及其受体系统在油酸致大鼠急性肺损伤中的变化和意义

目的:观察油酸(OA)致大鼠急性肺损伤(ALI)模型中,血管活性肽中介素(Intermedin,IMD)及其受体系统--降钙素受体样受体(CL)与受体活性修饰蛋白(RAMPs) 在肺组织中含量的变化及其病理意义.方法:尾静脉注射OA(0.2 mL/kg)制备大鼠ALI模型为OA组,测定大鼠动脉血氧分压(PaO2)、支气管肺泡灌洗液(BALF)中白细胞计数及中性粒细胞百分比(%PMN);放射免疫法测定血浆和肺组织匀浆IMD1-53含量; 半定量RT-PCR方法测定肺组织IMD,CL 和RAMP1,-2,-3 mRNA水平; 受体放射配体结合实验检测肺浆膜125I-IMD1-53受体结合力.结果:与正常对照组比较,油酸组大鼠血浆及肺组织匀浆中IMD1-53含量分别下降20.8%和74.5%(均P＜0.05);肺组织IMD,CL,RAMP1,RAMP2的mRNA表达水平分别下降30%,38%,26%和37.9%(均P＜0.01),肺组织中IMD与其受体系统mRNA变化水平有一定的相关性.125I- IMD1-53受体最大结合位点增加.肺组织、血浆中IMD浓度与PaO2呈正相关,与BALF中%PMN呈负相关(P＜0.01或0.05).结论:油酸致急性肺损伤大鼠肺组织IMD1-53含量降低,IMD,CL 和RAMP1,-2,-3基因表达有不同程度的降低,提示IMD及其受体系统参与了OA致急性肺损伤的发病过程.

Alterations of intermedin and its receptor system in oleic acid-induced acute lunginjury of rats

Objective:To investigate the changes of pulmonary IMD and its receptor system - calcitonin receptor-like receptor (CL) and receptor activity modifying proteins (RAMPs) mRNA in acute lung injury(ALI) induced by oleic acid of rats. Methods: Contents of IMD in plasma and lung homogenates were measured by radioimmunoassay(RIA). The lung mRNA of IMD, CL and RAMPs was determined by semi-quantitative RT-PCR. Results: Compared with control group, in ALI group, the contents of IMD_ 1-53 in plasma and lung homogenates were decreased by 20.8% and 74.5% (all P<0.05) , respectively. Furthermore , it was found that the levels of IMD, CL, RAMP1 and RAMP2 mRNA in lung were decreased by 30%,38%,26% and 37.9%(all P<0. 05) , respectively. The levels of CL , RAMP1 or RAMP2 mRNA were positively correlated with down-regulations of IMD mRNA in ALI. However, compared with control group, the maximum binding capacity of IMD_ 1-53 to plasma membranes was significantly increased in ALI group, and the affinity of IMD_ 1-53 for its receptor almost had no change. Conclusion: The amount of IMD_ 1-53 is down-regulated and IMD receptor system also down-regulated in Oliec acid induced ALI of rats. These changes suggest that IMD and its receptor system probably are involved in the development of ALI.