【摘要】：小膠質(zhì)細胞是中樞神經(jīng)系統(tǒng)中一種重要的細胞組分,在嚙齒類動物中,其數(shù)量占膠質(zhì)細胞總數(shù)的5%-20%。作為中樞神經(jīng)系統(tǒng)中特異性的免疫效應(yīng)細胞,小膠質(zhì)細胞在維持中樞神經(jīng)系統(tǒng)平衡中起到關(guān)鍵性的作用。在病理條件下,小膠質(zhì)細胞會快速活化,并在損傷區(qū)周圍聚集。在本實驗中,結(jié)合CX3CR1CreER/+:R26iDTO/+轉(zhuǎn)基因小鼠和光化學(xué)栓塞模型,探究了在特異性殺死小膠質(zhì)細胞后,新生小膠質(zhì)細胞的來源,并分析了在中風(fēng)損傷中小膠質(zhì)細胞和星形膠質(zhì)細胞的活化反應(yīng),并進一步研究了中風(fēng)后神經(jīng)元的死亡和存活。通過將攜帶Rosa26-stop-DTR (R26iDTR)等位基因的小鼠和在小膠質(zhì)細胞中表達他莫昔芬誘導(dǎo)Cre重組酶的CX3CR1CreER小鼠相雜交,獲得CX3CR1CreER/+:R26iDTR/+轉(zhuǎn)基因小鼠。通過他莫昔芬和白喉毒素(DT)的處理,使得CX3CR1CreER/+:R26iDTO/+轉(zhuǎn)基因小鼠表達白喉毒素受體(DTR),從而使小膠質(zhì)細胞對白喉毒素的敏感性加強,建立特異性殺死小膠質(zhì)細胞的體系。實驗結(jié)果表明,在進行他莫昔芬和白喉毒素的處理后,轉(zhuǎn)基因鼠中Iba-1陽性細胞的數(shù)量減少了90.7%；此后,小膠質(zhì)細胞的數(shù)量會逐漸增加,并在數(shù)周內(nèi)恢復(fù)至正常水平。本文的研究結(jié)果表明,新生小膠質(zhì)細胞來源于本地小膠質(zhì)細胞的增殖；選擇性殺死小膠質(zhì)細胞可導(dǎo)致海馬區(qū)域星形膠質(zhì)細胞的急性活化,但尼氏染色結(jié)果表明神經(jīng)元變化不明顯,而中風(fēng)后,不僅可引起星形膠質(zhì)細胞的活化,而且會導(dǎo)致退行性神經(jīng)元數(shù)量的增加。因而,小膠質(zhì)細胞的缺失對正常大腦神經(jīng)結(jié)構(gòu)的完整性影響不大,但在中風(fēng)條件下對膠質(zhì)細胞的激活和神經(jīng)元的退行性變化產(chǎn)生了一些影響。本論文的研究為腦中風(fēng)的治療提供了一些參考依據(jù)。
[Abstract]:Microglia is an important cellular component in the central nervous system. In rodents, the number of microglia accounts for 5- 20% of the total number of glial cells. As specific immune effector cells in the central nervous system, microglia play a key role in maintaining the central nervous system balance. Under pathological conditions, microglia are rapidly activated and congregate around the injured area. In this study, CX3CR1CreER/: R26iDTO/ transgenic mice and photochemical embolization model were used to investigate the origin of newborn microglia after specific killing of microglia. The activation of microglia and astrocytes in apoplectic injury was analyzed, and the death and survival of neurons after stroke were further studied. CX3CR1CreER/: R26iDTR/ transgenic mice were obtained by hybridization between mice carrying Rosa26-stop-DTR (R26iDTR) allele and CX3CR1CreER mice expressing tamoxifen induced Cre recombinant enzyme in microglia. Through the treatment of tamoxifen and diphtheria toxin (DT), CX3CR1CreER/: R26iDTO/ transgenic mice expressed diphtheria toxin receptor (DTR), which enhanced the sensitivity of microglia to diphtheria toxin and established a specific killing system for microglia. The results showed that after treatment with tamoxifen and diphtheria toxin, the number of Iba-1 positive cells in transgenic mice decreased 90.7 and the number of microglia increased gradually and returned to normal level within a few weeks. The results of this study indicate that the newborn microglia are derived from the proliferation of native microglia, and selective killing of microglia can lead to acute activation of astrocytes in the hippocampal region. However, the results of Nissl staining showed that the changes of neurons were not obvious. After stroke, not only the activation of astrocytes was induced, but also the number of degenerative neurons was increased. Therefore, the absence of microglia has little effect on the integrity of normal cerebral nerve structure, but has some effect on the activation of glial cells and the degeneration of neurons under stroke. This paper provides some references for the treatment of cerebral apoplexy.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R743.3

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