SUBSTANCE P AND THE PATHOGENESIS OF CRYPTOSPORIDIOSIS IN AIDS

P 物质与艾滋病隐孢子虫病的发病机制

• 批准号: 7716217
• 负责人: PREMA ROBINSON
• 金额: $ 6.33万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716217
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Back; Computer Retrieval of Information on Scientific Projects Database; Cryptosporidiosis; Cryptosporidium; Cryptosporidium parvum; Diarrhea; Enzyme-Linked Immunosorbent Assay; Fluorescence; Funding; Glycine decarboxylase; Grant; Immunohistochemistry; Infection; Institution; Intestines; Life; Macaca; Measures; Messenger RNA; Methods; Microscopy; Modeling; Pathogenesis; Patients; Physiological; Propionibacterium acnes; Proteins; Research; Research Personnel; Resources; Role; SIV; Source; Substance P; Substance P Receptor; Techniques; Therapeutic Corynebacterium Parvum; Tissues; United States National Institutes of Health; jejunum; paraform

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Back ground: Cryptosporidium infection leads to life threatening diarrhea in AIDS patients. Pathogenesis of cryptosporidiosis is due to intestinal physiological alterations. We devised an ex-vivo model using ex-vivo C. parvum infection of jejunal tissues derived from SIV infected macaques and studied the role of substance P (SP) in the pathogenesis of cryptosporidiosis. Methods: We measured jejunal SP mRNA and protein levels using ELISA , and electrophysiological alterations using the Ussing chamber technique in an ex-vivo model of Cryptosporidium infection. Paraformaldehyde fixed jejunum from SIV infected macaques with and without naturally-occurring cryptosporidiosis was studied for SP expression by immunohistochemistry and fluorescence deconvolution microscopy. Results: Ex-vivo Cryptosporidium infected tissues and tissues from SIV infected macaques with naturally-occurring cryptosporidiosis demonstrated elevated SP protein levels compared to tissues from SIV-infected animals without ex-vivo C. parvum infection or tissues from SIV-infected animals that have no evidence of cryptosporidiosis. In our ex-vivo model of Cryptosporidium infection, we demonstrated pathophysiological alterations that were blocked by SP-receptor antagonist treatment. Conclusions: These studies suggest that SP-receptor antagonists could prove useful for treatment of AIDS related cryptosporidiosis.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 背景：隐孢子虫感染会导致艾滋病患者出现危及生命的腹泻。隐孢子虫病的发病机制是由于肠道生理改变。我们利用 SIV 感染的猕猴的空肠组织进行体外感染，设计了体外模型，并研究了 P 物质 (SP) 在隐孢子虫病发病机制中的作用。 方法：我们使用 ELISA 测量了空肠 SP mRNA 和蛋白质水平，并使用 Ussing 室技术在隐孢子虫感染的离体模型中测量了电生理变化。通过免疫组织化学和荧光解卷积显微镜研究了来自 SIV 感染的有或没有自然发生的隐孢子虫病的猕猴的多聚甲醛固定空肠的 SP 表达。 结果：离体隐孢子虫感染的组织和患有自然发生的隐孢子虫病的 SIV 感染猕猴的组织与未离体隐孢子虫感染的 SIV 感染动物的组织或未受离体隐孢子虫感染的 SIV 感染动物的组织相比，SP 蛋白水平升高。隐孢子虫病的证据。在隐孢子虫感染的离体模型中，我们证明了 SP 受体拮抗剂治疗可阻断的病理生理学改变。 结论：这些研究表明 SP 受体拮抗剂可用于治疗艾滋病相关的隐孢子虫病。