肾上腺髓质素前体不同活性肽段在肺动脉高压大鼠肺内的变化  

Change of different active peptide fragments derived from proadreno medullin in pulmonary hypertension rats′ lung

作　　者：赵翠芬[1] 王丽娟[2] 王志宇[3] 夏伟[1] 王玉玮[1] 王荣[4] 

机构地区：[1]山东大学齐鲁医院小儿内科 [2]山东大学医学院,山东济南250012 [3]山东省医药生物技术研究中心,山东济南250062 [4]山东大学齐鲁医院卫生部教育部心血管重塑与功能研究重点实验室

出　　处：《中国病理生理杂志》2008年第4期655-660,共6页Chinese Journal of Pathophysiology

基　　金：山东省优秀中青年科学家科研奖励基金资助项目(No2005BS02003)

摘　　要：目的:检测肾上腺髓质素前体不同活性肽段在左向右分流肺动脉高压中肺内的分布和变化,探讨左向右分流肺动脉高压的发病机制。方法:选择30只雄性Wistar大鼠,随机分为实验组(n=15),对照组(n=15)。用自制套管将实验组大鼠左侧颈外静脉和颈总动脉连接,术后8周测定大鼠肺动脉收缩压(sPAP,用右心室收缩压来代替)、右心室与(左心室+室间隔)重量比[RV/(LV+SP)]、肺组织中等血管中膜厚度占血管直径百分比(MT%)。免疫组化法测定肺组织ADM、ADT、PAMP的分布,RT-PCR法测定肺组织PAMP、ADM、ADT、proADM45-92mRNA的表达。结果:①实验组大鼠肺动脉压高于对照组(P<0.05)。②ADM与ADT在肺内的分布较一致,但是2者相对含量的变化却相反。PAMP在大鼠肺内的分布与前2者差异显著。③左向右分流大鼠肺组织ADMmRNA表达水平高于对照组(P<0.01),ADTmRNA表达低于对照组(P<0.01)。结论:肾上腺髓质素前体不同活性肽段在左向右分流肺动脉高压大鼠肺组织中的变化为其分子内调控学说提供了有力的证据。AIM： To investigate the pathogenesis of pulmonary hypertension due to left to right shunt, the change and the distribution of active peptide fragments derived from proadrenomedullin was measured. METHODS ： Thirty male Wistar rats were selected and divided into 2 groups randomly, 15 of them were as control group, and the other as experiment group. A cervical left to right shunt pulmonary hypertension model was established by using a cuff technique, which connected the left jugular vein and the total cervical artery in experiment group. Eight weeks later,the systolic pulmonary artery pressure was measured （sPAP, replaced by right ventricular systolic pressure）. Morphologic assessments included the measurements of the weight ratio of right ventricle （RV） to left ventricle plus septum （LV ＋ SP） and the mean percentage of media wall thickness （ MT% ） in moderate size pulmonary arteries. The distributions of adrenomedullin （ ADM）, adrenotensin（ADT） and proadrenomedullin - N - peptide （PAMP） were measured by immunohistochemical staining. The mRNA expression levels of ADM, ADT, PAMP and proADM45 - 92 were tested by reverse transcription - polymerase chain reaction （RT- PCR）. RESULTS： ① The sPAP increased in experiment group （P 〈0. 05 ） compared with that of control group. ② The distribution of ADM and ADT in lung was almost the same, however, their protein content changed reversely; the distribution of PAMP was different from them. ③ The mRNA expression level of ADM increased （P 〈 0. 01 ）, but the expression level of ADT mRNA was decreased （P 〈 0. 01 ）. CONCLUSION： The change and distribution of different active peptide fragments derived from proadrenomedullin in pulmonary hypertension rats due to left tofight shunt provide powerful evidence for its intramolecular regulation theory.

关 键 词：肾上腺髓质素前体 肺动脉高压 

分 类 号：R363[医药卫生—病理学]