肾上腺髓质素抑制溶血磷脂酸诱导的大鼠主动脉外膜增殖  

Adrenomedullin inhibits proliferation of rat adventitia induced by lysophosphatidic acid

作　　者：杨靖辉[1] 蒋维[2] 潘春水[3] 齐永芬[2] 伍期专[1] 蔡大勇[2] 庞永正[1] 唐朝枢[1,4,5] 

机构地区：[1]北京大学第一医院心血管研究所 [2]北京大学医学部生理病理生理学系 [3]北京大学心血管分子生物学教育部重点实验室 [4]北京大学心血管分子生物学教育部重点实验室,北京100034 [5]北京大学医学部生理病理生理学系,北京100083

出　　处：《中国病理生理杂志》2005年第11期2091-2096,共6页Chinese Journal of Pathophysiology

基　　金：国家重大基础研究发展规划项目(973)基金资助项目(No.G2000056905)

摘　　要：目的观察溶血磷脂酸(LPA)和肾上腺髓质素(ADM)之间的相互作用对大鼠主动脉外膜增殖的影响。方法分别以放射免疫方法和RT-PCR方法检测主动脉外膜ADM的生成释放量及其mRNA水平的变化,同时用[3H]-TdR的掺入量表示血管外膜的增殖程度。结果5、10、20μmol/L的LPA呈浓度依赖性刺激血管外膜[3H]-TdR的掺入及ADM分泌,且高浓度和低浓度LPA均上调ADM基因表达。外源性ADM呈浓度依赖性抑制LPA的促外膜增殖作用,分别以ADM受体阻断剂ADM22-52及CGRP8-37与LPA共孵育可明显增强LPA的促增殖作用。结论LPA呈浓度依赖性刺激主动脉外膜合成分泌ADM,并上调其mRNA表达,生成的ADM反过来抑制了LPA诱导的外膜增殖效应。AIM： Lysophosphatidic acid （LPA） is a bioactive phospholipid known to have growth factor- like activity on fibroblasts, and is involved in cardiovascular diseases. Besides direct effects, usually, LPA can work together with other bioacrive factors to regulate cardiovascular homeostasis by induction of their expression and production, or increase in their activity. Among variety of bioactive factors, adrenomedullin （ADM） is a multifunctional peptide with an important cytoprotective effect against cardiovascular damage, but the interaction between ADM and LPA on adventitia remains unknown. METHODS： The experiment was performed on the bath of isolated rat aortic adventitia, ADM produced and secreted from adventitia stimulated by LPA was detected by using radioimmunoassay, proliferation in adventitia cells was evaluated by the level of [^3H] - thymine incorporation, and prepro ADM gene expression was measured by semi - quantitative reverse transcriptase polymerase chain reaction. RESULTS： It was found that LPA stimulated aorlic adventitia to secrete ADM and express its mRNA in a concentration - dependent manner. ADM inhibited LPA- induced proliferation in adventitial cells, and attenuated the activity of mitogen activated protein kinase （MAPK） stimulated by LPA. In contrast, the treatment with specific antagonists of ADM receptor potentiated the LPA - induced proliferation in adventitial cells. CONCLUSION： 12A stimulates adventitia to produce and secrete ADM, and in turn, ADM produced by adventitia regulates the vascular biological effects of LPA.

关 键 词：溶血磷脂酸 肾上腺髓质素 动脉 大鼠 

分 类 号：R363[医药卫生—病理学]