Alternate Day Calorie Restriction Improves Systemic Inflammation in a Mouse Model of Sepsis Induced by Cecal Ligation and Puncture
Alternate Day Calorie Restriction Improves Systemic Inflammation in a Mouse Model of Sepsis Induced by Cecal Ligation and Puncture
复制标题
DOI：
10.1016/j.jss.2010.11.883
复制
发表时间：
2012-05-01
影响因子：
2.2
通讯作者：
Noguchi, Takayuki
中科院分区：
文献类型：
--
作者：
Hasegawa, Akira;Iwasaka, Hideo;Noguchi, Takayuki
背景热量限制（CR）通过上调生存因子（如哺乳动物雷帕霉素靶蛋白（mTOR）、沉默调节蛋白和过氧化物酶体增殖物激活受体-g共激活因子1 α（PGC-1 α））发挥细胞保护作用。这些存活因子在减弱炎症反应中具有公认的作用。然而，目前尚不清楚CR是否影响脓毒症相关炎症。本研究的目的是确定CR是否影响盲肠结扎穿孔（CLP）诱导的脓毒症小鼠模型中脓毒症诱导的炎症。雄性C57 BL/6 N小鼠在CLP诱导的脓毒症之前进行隔日热量限制或正常喂养8天。诱导脓毒症后，检测肝、肺组织病理学变化，检测血清细胞因子和生存因子水平。血清细胞因子和高迁移率族蛋白1（HMGB 1）水平较低的动物进行隔日热量限制相比，正常喂养的小鼠CLP后。隔日卡路里限制也增加了sirtuin，PGC-1a和mTOR的水平。CLP组中80%的小鼠在CLP后48小时内死亡，而ACR D CLP组中50%的小鼠在CLP后48小时内死亡（P
Background. Calorie restriction (CR) exerts cyto-protective effects by up-regulating survival factors, such as mammalian target of rapamycin (mTOR), sirtuin, and peroxisome proliferator-activated receptor-g co-activator 1 alpha (PGC-1 alpha). These survival factors have well-established roles in attenuating the inflammatory response. However, it is unclear whether CR affects sepsis-related inflammation. The purpose of this study was to determine whether CR affects sepsis-induced inflammation in a cecal ligation and puncture (CLP)-induced mouse model of sepsis.Methods. Male C57BL/6N mice underwent alternate day calorie restriction or normal feeding for 8 d before CLP-induced sepsis. After induction of sepsis, liver and lung histopathology and serum levels of cytokines and survival factors were assessed.Results. Serum cytokine and high mobility group box protein 1 (HMGB1) levels were lower in animals that underwent alternate day calorie restriction compared with normally-fed mice after CLP. Alternate day calorie restriction also increased levels of sirtuin, PGC-1a, and mTOR. While 80% of mice in the CLP group died within 48 h after undergoing CLP, 50% of mice died in the ACR D CLP group (P