Murakami Shinsuke, Nagaya Noritoshi, Itoh Takefumi, Iwase Takashi, Fujisato Toshiya, Nishioka Keisuke, Hamada Kaoru, Kangawa Kenji, Kimura Hiroshi
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Am J Respir Crit Care Med. 2005 Sep 1;172(5):581-9. doi: 10.1164/rccm.200409-1280OC. Epub 2005 Jun 9.
Adrenomedullin, a potent vasodilator peptide, regulates cell growth and survival. However, whether adrenomedullin contributes to lung regeneration remains unknown.
To investigate whether adrenomedullin influences the kinetics of bone marrow cells, and whether adrenomedullin promotes regeneration of alveoli and vasculature and thereby improves lung structure and function in elastase-induced emphysema in mice.
Adrenomedullin or vehicle was randomly administered to C57BL/6 mice for 5 days. We counted the numbers of mononuclear cells and stem cell antigen-1-positive cells in circulating blood. After intratracheal injection of elastase or saline, mice were randomized to receive continuous infusion of adrenomedullin or vehicle for 14 days. Functional and histologic analyses were performed 28 days after treatment.
Twenty-eight days after elastase injection, destruction of the alveolar walls was observed. However, adrenomedullin infusion significantly inhibited the increase in lung volume, static lung compliance, and mean linear intercept in mice given elastase. Adrenomedullin increased the numbers of mononuclear cells and stem cell antigen-1-positive cells in circulating blood. Adrenomedullin significantly increased the number of bone marrow-derived cells incorporated into the elastase-treated lung. Some of these cells were positive for cytokeratin or von Willebrand factor. Infusion of adrenomedullin after the establishment of emphysema also had beneficial effects on lung structure and function. In vitro, addition of adrenomedullin attenuates elastase-induced cell death in alveolar epithelial cells and endothelial cells.
Adrenomedullin improved elastase-induced emphysema at least in part through mobilization of bone marrow cells and the direct protective effects on alveolar epithelial cells and endothelial cells.
肾上腺髓质素是一种强效血管舒张肽，可调节细胞生长和存活。然而，肾上腺髓质素是否有助于肺再生仍不清楚。
研究肾上腺髓质素是否影响骨髓细胞动力学，以及肾上腺髓质素是否促进肺泡和血管再生，从而改善弹性蛋白酶诱导的小鼠肺气肿的肺结构和功能。
将肾上腺髓质素或赋形剂随机给予C57BL/6小鼠5天。我们计算循环血液中单核细胞和干细胞抗原-1阳性细胞的数量。气管内注射弹性蛋白酶或生理盐水后，将小鼠随机分组，连续输注肾上腺髓质素或赋形剂14天。治疗28天后进行功能和组织学分析。
弹性蛋白酶注射28天后，观察到肺泡壁破坏。然而，输注肾上腺髓质素显著抑制了给予弹性蛋白酶的小鼠肺体积、静态肺顺应性和平均线性截距的增加。肾上腺髓质素增加了循环血液中单核细胞和干细胞抗原-1阳性细胞的数量。肾上腺髓质素显著增加了整合到弹性蛋白酶处理的肺中的骨髓来源细胞的数量。其中一些细胞细胞角蛋白或血管性血友病因子呈阳性。肺气肿形成后输注肾上腺髓质素对肺结构和功能也有有益影响。在体外，添加肾上腺髓质素可减轻弹性蛋白酶诱导的肺泡上皮细胞和内皮细胞死亡。
肾上腺髓质素至少部分通过动员骨髓细胞以及对肺泡上皮细胞和内皮细胞的直接保护作用改善弹性蛋白酶诱导的肺气肿。
