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外周炎癥誘導(dǎo)下丘腦弓狀核神經(jīng)元c-fos表達(dá)及其機(jī)制

發(fā)布時(shí)間:2018-06-01 05:50

  本文選題:下丘腦弓狀核 + 痛覺(jué)過(guò)敏 ; 參考:《蘇州大學(xué)》2010年碩士論文


【摘要】:目的:本實(shí)驗(yàn)旨在觀察下丘腦弓狀核(hypothalamic arcuate nucleus, ARC)神經(jīng)元在外周炎癥時(shí)的激活狀態(tài)和被激活神經(jīng)元的化學(xué)性質(zhì),并探討NMDA受體和Src家族蛋白酪氨酸激酶在ARC神經(jīng)元激活及痛覺(jué)過(guò)敏中的作用。 方法:用完全弗氏佐劑建立大鼠外周炎癥模型;用輻射熱-縮腿法測(cè)定痛閾變化;免疫組織化學(xué)染色,檢測(cè)ARC中c-fos表達(dá),體視學(xué)無(wú)偏差測(cè)量系統(tǒng)計(jì)數(shù)Fos免疫反應(yīng)陽(yáng)性細(xì)胞;進(jìn)行酪氨酸羥化酶、谷氨酸囊泡轉(zhuǎn)運(yùn)體2或β-內(nèi)啡肽與Fos蛋白的雙重免疫組織化學(xué)染色,以明確ARC激活神經(jīng)元的化學(xué)性質(zhì)。用側(cè)腦室微量注射NMDA受體拮抗劑MK801或Src蛋白酪氨酸激酶抑制劑PP2,探討NMDA受體和Src蛋白酪氨酸激酶在下丘腦弓狀核神經(jīng)元激活中的作用。 結(jié)果:大鼠在注射佐劑后24小時(shí),即表現(xiàn)出熱縮腿潛伏期縮短(P0.01),出現(xiàn)痛覺(jué)過(guò)敏,注射佐劑后21天中ARC c-fos表達(dá)明顯上調(diào)(P0.01),神經(jīng)元處于激活狀態(tài)。在ARC中發(fā)現(xiàn)有酪氨酸羥化酶,β-內(nèi)啡肽或谷氨酸囊泡轉(zhuǎn)運(yùn)體2與Fos蛋白共表達(dá)的神經(jīng)元。側(cè)腦室注射MK801或者PP2可明顯延長(zhǎng)熱縮腿潛伏期,緩解痛覺(jué)過(guò)敏,并大幅減少ARC中c-fos表達(dá)。 結(jié)論:在外周炎癥引起痛覺(jué)過(guò)敏過(guò)程中,ARC神經(jīng)元明顯激活,激活狀態(tài)神經(jīng)元主要有β-內(nèi)啡肽、多巴胺與谷氨酸能神經(jīng)元。NMDA受體與Src蛋白酪氨酸激酶家族介導(dǎo)了ARC神經(jīng)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.
【學(xué)位授予單位】:蘇州大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2010
【分類號(hào)】:R363

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