SUBSTANCE P AND THE PATHOGENESIS OF CRYPTOSPORIDIOSIS IN AIDS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景： 隐孢子虫感染导致危及生命的腹泻艾滋病患者。隐孢子虫病的发病机制是由于肠道生理改变。我们设计了一个离体模型，使用离体C。本研究通过对SIV感染猕猴空肠组织进行隐孢子虫感染的研究，探讨了P物质（SP）在隐孢子虫病发病机制中的作用。 研究方法： 我们测量空肠SP的mRNA和蛋白质水平，采用ELISA和电生理学的改变，使用Ussing室技术在隐孢子虫感染的离体模型。通过免疫组织化学和荧光去卷积显微镜研究了SIV感染猕猴的空肠（有和没有自然发生的隐孢子虫病）的SP表达。 结果如下： 离体隐孢子虫感染的组织和来自具有天然存在的隐孢子虫病的SIV感染的猕猴的组织与来自没有离体隐孢子虫感染的SIV感染的动物的组织相比显示出升高的SP蛋白水平。细小孢子虫感染或来自SIV感染动物的组织，没有隐孢子虫病的证据。在我们的隐孢子虫感染的离体模型中，我们证明了SP受体拮抗剂治疗所阻断的病理生理学改变。 结论： 这些研究表明，SP受体拮抗剂可能被证明是有用的治疗艾滋病相关的隐孢子虫病。

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.