黄芪甲苷在盲肠末端结扎穿孔诱导脓毒症小鼠中的保护作用研究  

Study on protective effect of astragaloside Ⅳ in septic mice

作　　者：袁保红 黄萍 邓鑫梦 王柯英 戴良成[3] 尹辉 

机构地区：[1]广东药科大学基础学院广东省生物活性药物研究重点实验室,广东广州510006 [2]广东工业大学环境科学与工程学院,广东广州510006 [3]广东药科大学附属第一医院重症医学科,广东广州510080

出　　处：《中国药理学通报》2017年第10期1452-1456,共5页Chinese Pharmacological Bulletin

基　　金：广东省医学科学技术研究基金(No A2016226);广东省自然科学基金资助项目(No 2014A030313581;2015A030313581)

摘　　要：目的研究黄芪甲苷(astragaloside,AS-Ⅳ)在盲肠末端结扎穿孔(cecal ligation and puncture,CLP)诱导脓毒症小鼠中的免疫保护作用。方法将C57BL/6小鼠随机分成假手术组、CLP组、CLP+AS-Ⅳ组。造模术前2 d,CLP+AS-Ⅳ组灌胃给予AS-Ⅳ(10 mg·kg^(-1)),对照组给予等量生理盐水。建立小鼠CLP诱导的脓毒血症模型,在6、24 h分别取血液、腹腔液和组织器官进行细菌总数测定;采用Percoll密度梯度分离纯化外周血中性粒细胞,用Transwell法检测小鼠中性粒细胞的趋化功能;与E.coli混合培养检测中性粒细胞的杀菌功能。结果 AS-Ⅳ预处理的脓毒症小鼠存活率明显上升,腹腔液中性粒细胞数目明显增加;AS-Ⅳ处理后小鼠腹腔液、血液及肝、肺、肾等脏器中细菌负荷量明显降低;AS-Ⅳ预处理的中性粒细胞趋化和杀菌功能增强。结论黄芪甲苷对CLP诱导脓毒症小鼠具有免疫保护作用,其机制与上调中性粒细胞趋化因子受体CXCR2表达,增加中性粒细胞抗菌功能相关。Aim To study the effect of astragaloside（ AS-Ⅳ） in CLP-induced septic mice. Methods C57BL/6 mice were randomly divided into the sham group,CLP group and CLP ＋ AS-Ⅳ group. Two days before operation,AS-Ⅳ（ 10 mg·kg（-1）） solution was intragastrically administered into CLP ＋ AS-Ⅳ group,and the other groups were treated with normal saline.A sepsis model was established by cecal ligation and puncture（ CLP）. Blood,peritoneal fluid and tissue organs were collected at 6 h and 24 h. Neutrophils of blood were purified by Percoll density gradient. Transwell was used to detect the chemotaxis function of neutrophils. The killing activity of neutrophils was detected by coculture with E. coli. Results The survival rate of AS-Ⅳ-pretreated septic mice significantly increased. The number of neutrophils in peritoneal fluid was enhanced markedly. The number of bacteria in the peritoneal fluid,blood and tissue organs such as liver,lung and kidney significantly decreased after AS-Ⅳpretreatment. The chemotaxis and killing activity of neutrophils increased significantly in AS-Ⅳ-treated mice（ P〈 0. 05）. Conclusion Astragaloside displays an immunoprotective effect in CLP-induced septic mice,which is related to the upregulation of CXCR2 expression on neutrophils and the increase of neutrophil antibacterial activity.

关 键 词：黄芪甲苷 脓毒血症 中性粒细胞 CLP CXCR2 免疫调节 

分 类 号：R-332[医药卫生] R284.1