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	(Pro)renin receptor blocker improves survival of rats with sepsis.
掲載誌名	正式名：The Journal of surgical research 略　 称：J Surg Res ISSNコード：1095-8673(Electronic)0022-4804(Linking)
巻・号・頁	186(1),pp.269-77
著者・共著者	HIRANO Yuki†, TAKEUCHI Hiroya, SUDA Koichi, HAGIWARA Tomoko, MIYASYO Taku, KAWAMURA Yoshio, YAMADA Shingo, OYAMA Takashi, TAKAHASHI Tsunehiro, WADA Norihito, SAIKAWA Yoshiro, ICHIHARA Atsuhiro, KITAGAWA Yuko
発行年月	2014/01
概要	BACKGROUND:The renin-angiotensin system (RAS) affects inflammatory responses during sepsis. Nonproteolytic activation of prorenin by the (pro)renin receptor has recently been shown to stimulate the tissue RAS. In the present study, the effect of (pro)renin receptor blocker (PRRB) pretreatment on sepsis in a rat cecal ligation and puncture (CLP) model was investigated.MATERIALS AND METHODS:Male Sprague-Dawley rats underwent CLP and were randomly divided into two groups: PRRB-treated group and control peptide-treated group. Survival was analyzed for 7 d after CLP. The serum concentrations of cytokines and high-mobility group box chromosomal protein 1 (HMGB1) were measured at three time points (0, 3, and 6 h after CLP). Hematoxylin-eosin staining and immunohistochemical staining for nonproteolytically activated prorenin and HMGB1 were performed on the cecum to assess pathologic changes found 6 h after CLP.RESULTS:Treatment with PRRB improved the survival rate of the post-CLP septic rats (P = 0.023). PRRB also significantly reduced serum tumor necrosis factor-α, interleukin-1β, and HMGB1 levels 6 h after CLP. In CLP rats that were treated with control peptide, the expression of activated prorenin was elevated in peritoneal foam cells. Moreover, expression of HMGB1 was increased in peritoneal inflammatory cells. In contrast, bRESULTS:oth were markedly suppressed in CLP rats that were treated with PRRB.CONCLUSIONS:PRRB significantly improved the survival rate of rats with clinically relevant sepsis, possibly by attenuating a sepsis-induced systemic inflammatory response. We propose that overactivation of the RAS by activation of prorenin in foam cells may be a significant contributor to sepsis.
DOI	10.1016/j.jss.2013.08.004
文献番号	24011922