イチハラ　アツヒロ   ICHIHARA Atsuhiro   市原　淳弘    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade.
掲載誌名	正式名：Experimental lung research 略　 称：Exp Lung Res ISSNコード：01902148/15210499
巻・号・頁	41(4),pp.199-207
著者・共著者	ISHII Kenjiro†, TAKEUCHI Hiroya, FUKUNAGA Koichi, HIRANO Yuki, SUDA Koichi, HAGIWARA Tomoko, MIYASHO Taku, YAMADA Shingo, NAKAMURA Rieko, TAKAHASHI Tsunehiro, WADA Norihito, KAWAKUBO Hirofumi, SAIKAWA Yoshiro, OMORI Tai, BETSUYAKU Tomoko, ICHIHARA Atsuhiro, KITAGAWA Yuko
発行年月	2015/05
概要	PURPOSE/AIM:We performed a randomized, prospective animal study to investigate whether inhibiting the renin-angiotensin system with a (pro)renin receptor blocker (PRRB) prevents acute lung injury (ALI) in a rodent model.MATERIALS:We used Thirty-six male Sprague-Dawley rats. We administered lipopolysaccharide (LPS; 2 mg/kg) intratracheally with or without PRRB pretreatment (1 mg/kg/d).METHODS:We performed bronchoalveolar lavage (BAL) and lung removal at 4 h after LPS administration and measured levels of inflammatory cytokines, high mobility group box 1 (HMGB-1) protein, and total protein in bronchoalveolar lavage fluid (BALF). Myeloperoxidase (MPO) activity was detected in lung tissue homogenates using a sensitive ELISA. We performed hematoxylin and eosin staining and immunohistochemical staining for nonproteolytically activated prorenin in the left lung.RESULTS:The PRRB decreased leukocyte counts and total protein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, and IL-10 levels in the BALF and MPO activity in lung tissue. The PRRB reduced interstitial edema, hemorRESULTS:rhage, and the neutrophil count in the lung tissues. Consistent with the reduction in lung tissue damage, immunohistochemical staining showed that the PRRB decreased the amount of nonproteolytically activated prorenin.CONCLUSIONS:The PRRB blocked LPS-induced inflammatory response in the lung and protected against ALI. Therefore, it is a potential therapeutic agent for preventing ALI.
DOI	10.3109/01902148.2014.993444
PMID	25844689