EFFECTS OF MORPHINE ON A LIVE BACTERIAL INFECTION

吗啡对活细菌感染的作用

• 批准号: 6405545
• 负责人: Kelly A Carrigan-Simontacchi
• 金额: $ 2.48万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6405545
• 关键词: Bacteroides gingivalis; bacterial disease; bacterial vaccines; blood toxicology; enzyme activity; immunopharmacology; laboratory rat; microorganism immunology; morphine; naltrexone; nitrates; nitric oxide; nitric oxide synthase; nitrites; opioid receptor; polymerase chain reaction; western blottings

DESCRIPTION: (Provided by Applicant) The objective of the proposed experiments is to determine the effects of morphine treatment on the progression of a live bacterial infection in naive and immunized animals, and begin to understand the role of nitric oxide in that process. To achieve these goals, the proposed research uses a subcutaneous chamber model, whereby a stainless steel coil implanted subcutaneously in the rat serves as the site of injection of Porphyromonas gingivalis strain A7436 bacteria. In all studies, animals receive saline or morphine prior to introduction of live bacteria into the chamber. These studies investigate bacterial dissemination from the chamber to the blood, spleen, liver, and lung. The level of nitric oxide production will be determined by measuring the levels of inducible nitric oxide synthase mRNA and protein levels in the spleen, lung, and liver. Plasma nitrite/nitrate concentrations also will be determined. Specific Aim I determines the dose-dependent effect of morphine treatment on dissemination of P. gingivalis strain A7436 to blood and tissues and nitric oxide activity in naive animals. Specific Aim II determines the pharmacological specificity of morphine on bacterial dissemination and nitric oxide activity by assessing the effect of the opiate antagonist, naltrexone, administered prior to morphine treatment. Specific Aim III determines the effect of morphine on bacterial dissemination and nitric oxide activity in animals previously immunized with heat killed A7436 bacteria. The results of these studies will expand the known effects of morphine on immune function and provide a greater understanding of the effects of morphine on infection. The conduct of these experiments will afford the applicant with the opportunity to acquire research experience in the application of molecular and microbiological techniques to the study of the pharmacological effects of opioids on immune function and the study of infection.

描述：（由申请人提供） 所提出的实验的目的是确定的影响 吗啡治疗对幼稚活细菌感染进展的影响 和免疫动物，并开始了解一氧化氮在其中的作用 过程。为了实现这些目标，拟议的研究使用皮下注射 腔室模型，将不锈钢线圈植入皮下 大鼠作为牙龈卟啉单胞菌菌株 A7436 的注射部位 细菌。在所有研究中，动物在实验前接受盐水或吗啡。 将活细菌引入室内。这些研究调查 细菌从腔室传播到血液、脾脏、肝脏和肺。 一氧化氮产生的水平将通过测量水平来确定 诱导型一氧化氮合酶 mRNA 和蛋白水平在脾、肺、 和肝脏。血浆亚硝酸盐/硝酸盐浓度也将被测定。 具体目标 I 确定吗啡治疗的剂量依赖性效应 牙龈卟啉单胞菌菌株 A7436 传播到血液和组织以及硝酸盐 幼稚动物中的氧化物活性。具体目标 II 决定了药理学 吗啡对细菌传播和一氧化氮活性的特异性 评估阿片拮抗剂纳曲酮的效果，先给予 吗啡治疗。具体目标 III 确定吗啡对 先前动物体内的细菌传播和一氧化氮活性 热免疫杀死了 A7436 细菌。这些研究的结果将 扩大吗啡对免疫功能的已知影响并提供更大的作用 了解吗啡对感染的影响。这些行为的 实验将为申请人提供获得研究的机会 应用分子和微生物技术的经验 阿片类药物对免疫功能的药理作用及其作用的研究 感染研究。