SURGERY AND IV NUTRITION MODULATE MACROPHAGE FUNCTION

手术和静脉营养调节巨噬细胞功能

• 批准号: 2392216
• 负责人: W SCOTT HELTON
• 金额: $ 10.4万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2392216
• 关键词: alveolar macrophages; cytokine; dietary lipid; disease /disorder proneness /risk; immunocytochemistry; injury /disease stressor; laboratory rat; macrophage; multiple organ failure; neuroendocrine system; nutrition related tag; parenteral feedings; postoperative complications; superoxides; surgery; wound infection

The long term objectives of this application are to improve host defense in critically ill surgical patients as a means for preventing or attenuating the deleterious consequences of infection during intravenous feeding (TPN). TPN is immunosuppressive and predisposes to hospital acquired infection by unclear mechanisms. Infection in TPN-fed patients results in an altered neuroendocrine and catabolic response which may contribute to multiple organ failure and increased mortality during surgical critical illness. The roles that the macrophage (Mphi) sympathetic and hypothalamic- pituitary-adrenal axis play in mediating these pathophysiologic events during TPN are incompletely understood. Studies are proposed to investigate the hypothesis that TPN activates the sympathoadrenal, sympathetic nervous and hypothalamic pituitary -adrenal axis play in mediating these pathophysiologic events during TPN are incompletely understood. Studies are proposed to investigate the hypothesis that TPN activates the sympathoadrenal, sympathetic nervous and hypothalamic pituitary adrenal axis and impairs Mphi function. Mphis will be isolated from the mesenteric lymph nodes, peritoneal cavity, lung, and spleen and their function studied. Mphi functions to be studied include: 1) ability to kill bacteria, 2) production of superoxide anion; and 3) basal and lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor (TNF), Prostaglandin E2 (PGE2), and procoagulant activity (PCA). Immunohistochemistry will be used to count the number of Mphis in the gut wall. Quantitative northern assays of Mphi TNF and PCA mRNA will be performed on unsolicited mphis from the peritoneal cavity, lung, spleen and mesenteric lymph nodes and used as an indirect marker of Mphi activation and exposure to LPS. Mphi fatty acid composition will be measured and correlated with specific functions and alterations in cytokine responses to LPS. Mesenteric lymph nodes will be cultured for bacteria. Sympathoadrenal and sympathetic nervous activity will be assessed by measuring urinary catecholamine excretion and tissue norepinephrine content and turnover respectively. Activation of the hypothalamic-pituitary- adrenal axis will be indirectly assessed by measuring serum corticosterone. Mphi functions and bacterial translocation to mesenteric lymph nodes will be correlated with plasma corticosterone, urinary catecholamine excretion, tissue norepinephrine content and tissue norepinephrine turnover. Studies will investigate several mechanisms of TPN-induced stress a d macrophage dysfunction and include: oral antibiotic gut decontamination, intravenous polymixin B, partial duodenal nutrition, ingestion of a non digestible non-nutritious meal, chewing on a metal spoon, and anatomic sympathectomy. It is hypothesized that all of these interventions will improve Mphi function decrease bacterial translocation to MLN, and attenuate sympathetic, sympathoadrenal, and hypothalamic-pituitary adrenal activation during TPN. Fundamental knowledge of the physiologic effects of TPN on Mphi function and the neuroendocrine system are potentially useful in the development of therapies for the prevention of sepsis and multiple organ failure in TPN-fed critically ill surgical patients.

此应用程序的长期目标是改善主机防御 重症手术患者作为预防或衰减的手段 静脉喂养过程中感染的有害后果（TPN）。 TPN是免疫抑制性的，易于接受医院的感染 不清楚的机制。 TPN喂养患者的感染导致改变 神经内分泌和分解代谢反应可能有助于多重 器官衰竭和手术危重疾病期间的死亡率增加。 巨噬细胞（MPHI）交感神经和下丘脑的作用 垂体 - 肾上腺轴在介导这些病理生理事件中发挥作用 在TPN期间未完全理解。 提出了研究以研究TPN激活的假设 交感神经，交感神经和下丘脑垂体 - 肾上腺 轴在TPN期间介导这些病理生理事件的轴是 不完全理解。 提出了研究以研究TPN激活的假设 交感神经，交感神经和下丘脑垂体肾上腺 轴并损害MPHI功能。 MPHI将从肠系膜中分离出来 淋巴结，腹膜腔，肺和脾脏及其功能 研究。 MPHI函数要研究的功能包括：1）杀死的能力 细菌，2）产生超氧化阴离子； 3）基础和 脂多糖（LPS）刺激的肿瘤坏死因子（TNF）的释放， Prostaglandin E2（PGE2）和Procogulant活性（PCA）。 免疫组织化学将用于计算肠道中的MPHI数量 墙。 MPHI TNF和PCA mRNA的定量北部测定法将是 从腹膜腔，肺，脾和 肠系膜淋巴结，用作MPHI激活的间接标记 和暴露于LPS。 将测量mphi脂肪酸成分，并 与特定功能和细胞因子反应的改变相关 LPS。 肠系膜淋巴结将用于细菌。 交感神经和交感神经活动将由 测量儿茶酚胺排泄和组织去甲肾上腺素含量 和营业额分别。 下丘脑 - 垂体激活 肾上腺轴将通过测量血清皮质酮间接评估。 MPHI功能和细菌易位到肠系膜淋巴结将 与等离子体皮质酮，尿尿catecholamine排泄相关， 组织去甲肾上腺素含量和组织去甲肾上腺素的周转率。 研究将研究TPN诱导的应力A D的几种机制 巨噬细胞功能障碍，包括：口服抗生素肠道污染， 静脉注射多晶蛋白B，部分十二指肠营养，摄入非 可易消化的非肉餐，咀嚼金属勺和解剖学 交感神经切除术。 假设所有这些干预措施将 提高MPHI功能可将细菌易位降低到MLN，并 衰减交感神经，交感神经和下丘脑垂体肾上腺 TPN期间的激活。 对生理影响的基本知识 TPN在MPHI功能和神经内分泌系统上可能有用 在开发预防败血症和多重疗法方面 TPN喂养的重症手术患者的器官衰竭。