外周炎症诱导下丘脑弓状核神经元c-fos表达及其机制

发布时间：2018-06-01 05:50

本文选题：下丘脑弓状核 + 痛觉过敏　；参考：《苏州大学》2010年硕士论文

【摘要】：目的:本实验旨在观察下丘脑弓状核(hypothalamic arcuate nucleus, ARC)神经元在外周炎症时的激活状态和被激活神经元的化学性质,并探讨NMDA受体和Src家族蛋白酪氨酸激酶在ARC神经元激活及痛觉过敏中的作用。方法:用完全弗氏佐剂建立大鼠外周炎症模型;用辐射热-缩腿法测定痛阈变化;免疫组织化学染色,检测ARC中c-fos表达,体视学无偏差测量系统计数Fos免疫反应阳性细胞;进行酪氨酸羟化酶、谷氨酸囊泡转运体2或β-内啡肽与Fos蛋白的双重免疫组织化学染色,以明确ARC激活神经元的化学性质。用侧脑室微量注射NMDA受体拮抗剂MK801或Src蛋白酪氨酸激酶抑制剂PP2,探讨NMDA受体和Src蛋白酪氨酸激酶在下丘脑弓状核神经元激活中的作用。结果:大鼠在注射佐剂后24小时,即表现出热缩腿潜伏期缩短(P0.01),出现痛觉过敏,注射佐剂后21天中ARC c-fos表达明显上调(P0.01),神经元处于激活状态。在ARC中发现有酪氨酸羟化酶,β-内啡肽或谷氨酸囊泡转运体2与Fos蛋白共表达的神经元。侧脑室注射MK801或者PP2可明显延长热缩腿潜伏期,缓解痛觉过敏,并大幅减少ARC中c-fos表达。结论:在外周炎症引起痛觉过敏过程中,ARC神经元明显激活,激活状态神经元主要有β-内啡肽、多巴胺与谷氨酸能神经元。NMDA受体与Src蛋白酪氨酸激酶家族介导了ARC神经元的激活。
[Abstract]:Aim: to investigate the activation state and chemical properties of hypothalamic arcuate nucleus, ARC) neurons in hypothalamic arcuate nucleus during peripheral inflammation. To investigate the role of NMDA receptor and Src family protein tyrosine kinase in the activation of ARC neurons and hyperalgesia. Methods: the peripheral inflammatory model of rats was established with complete Freund's adjuvant, the pain threshold was measured by radiative heat contraction method, the expression of c-fos in ARC was detected by immunohistochemical staining, and the positive cells of Fos immunoreactive cells were counted by stereology without deviation measurement system. Double immunohistochemical staining of tyrosine hydroxylase, glutamate vesicle transporter 2 or 尾 -endorphin and Fos protein was performed to clarify the chemical properties of ARC activated neurons. NMDA receptor antagonist MK801 or Src protein tyrosine kinase inhibitor PP2were microinjected into the lateral ventricle to investigate the role of NMDA receptor and Src protein tyrosine kinase in the activation of arcuate nucleus neurons in the hypothalamus. Results: 24 hours after the injection of adjuvant, the rats showed that the latent period of heat contraction was shortened (P 0.01), and the hyperalgesia appeared. The expression of ARC c-fos was upregulated significantly in 21 days after the injection of adjuvant, and the neurons were activated. Tyrosine hydroxylase, 尾 -endorphin or glutamate vesicle transporter 2 were found to co-express with Fos protein in ARC. Intracerebroventricular injection of MK801 or PP2 significantly prolonged the latent period of heat contraction, alleviated hyperalgesia, and significantly reduced the expression of c-fos in ARC. Conclusion: during the process of hyperalgesia induced by peripheral inflammation, the neurons of the ARC were activated, and the activation state neurons were mainly 尾 -endorphin. The activation of ARC neurons was mediated by the family of dopamine and glutaminergic neurons. NMDA receptors and Src protein tyrosine kinase family.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R363

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