發(fā)布時(shí)間：2018-04-30 09:18

  本文選題：延遲亞低溫 + 神經(jīng)發(fā)生�。� 參考：《浙江大學(xué)》2016年碩士論文

【摘要】：研究背景：對(duì)于缺血腦損傷,亞低溫治療是一種強(qiáng)大的神經(jīng)保護(hù)策略。但病人往往是發(fā)病后才運(yùn)送到醫(yī)療單位,延誤了“最佳”低溫治療時(shí)機(jī)。這種延遲亞低溫是否能促進(jìn)神經(jīng)功能恢復(fù)及其機(jī)制需要進(jìn)一步闡明。神經(jīng)發(fā)生(neurogenesis)是一種可能的低溫保護(hù)機(jī)制。腦缺血后側(cè)腦室室管膜下區(qū)(SVZ)和海馬齒狀回(DG)區(qū)細(xì)胞增殖增加；神經(jīng)祖細(xì)胞遷移途徑發(fā)生了改變,大量新增殖的細(xì)胞遷移至缺血損傷邊緣；一小部分細(xì)胞能存活并分化為成熟的神經(jīng)元或星形膠質(zhì)細(xì)胞。缺血后亞低溫能抑制氨基酸和單胺神經(jīng)遞質(zhì)的過(guò)度釋放、及炎癥反應(yīng),但是否調(diào)節(jié)缺血后神經(jīng)前體細(xì)胞的增殖和遷移還知之甚少。本課題首先探討缺血后延遲亞低溫對(duì)腦梗死面積和神經(jīng)功能恢復(fù)的影響；其次研究檢測(cè)腦缺血后延遲亞低溫對(duì)細(xì)胞增殖和分化的影響。方法：制備局灶性腦缺血再灌注模型,缺血再灌注后15mmin降低中心溫度到30℃維持3h來(lái)誘導(dǎo)延遲亞低溫。應(yīng)用行為學(xué)測(cè)試、溴脫氧尿苷(BrdU)標(biāo)記、激光共聚焦顯微鏡細(xì)胞譜分析等方法來(lái)探討延遲亞低溫治療對(duì)神經(jīng)功能恢復(fù)和神經(jīng)發(fā)生的影響。結(jié)果：延遲亞低溫不能降低缺血梗死面積,但能促進(jìn)神經(jīng)功能恢復(fù)。同常溫模型組相比,延遲亞低溫能顯著提高腦缺血后3h(缺血后立即給予BrdU標(biāo)記一次)缺血側(cè)SVZ區(qū)的新生細(xì)胞數(shù)(P0.05)。延遲亞低溫能顯著提高缺血后7和14d(缺血后給予BrdU連續(xù)7d標(biāo)記)缺血側(cè)SVZ區(qū)的新生細(xì)胞積聚數(shù)(P0.05)；延遲亞低溫能顯著提高缺血后7d缺血側(cè)DG區(qū)的新生細(xì)胞積聚數(shù)(P0.05),卻顯著降低14d缺血側(cè)DG區(qū)的新生細(xì)胞積聚數(shù)(P0.05)；對(duì)缺血半梗死區(qū)新生細(xì)胞聚集無(wú)明顯影響。另外,延遲亞低溫能提高缺血后一些時(shí)間點(diǎn)新生細(xì)胞與一些神經(jīng)細(xì)胞標(biāo)記物共定位的比例,包括DCX(未成熟神經(jīng)元標(biāo)記物)、Nestin(未成熟神經(jīng)元或膠質(zhì)細(xì)胞標(biāo)志物)、GFAP (成熟星形膠質(zhì)細(xì)胞標(biāo)記物)、NG2(少突膠質(zhì)細(xì)胞標(biāo)記物)和NeuN(成熟神經(jīng)元標(biāo)記物)。結(jié)論：(1)延遲亞低溫可促進(jìn)神經(jīng)功能恢復(fù)。(2)延遲亞低溫可通過(guò)促進(jìn)缺血后細(xì)胞增殖和新生細(xì)胞積聚、改變新生細(xì)胞的最終命運(yùn)來(lái)減輕缺血性損傷、促進(jìn)腦損傷的修復(fù)。
[Abstract]:Background: mild hypothermia therapy is a powerful neuroprotective strategy for ischemic brain injury. But patients are often transported to medical units after onset, delaying the "best" timing of hypothermia treatment. Whether this delayed mild hypothermia can promote the recovery of neural function and its mechanism need further clarification. Neurogenetics is a possible hypothermia protective mechanism. After cerebral ischemia, the proliferation of SVZ (subependymal area) and DGG (dentate gyrus) increased, the migration pathway of neural progenitor cells changed, and a large number of newly proliferated cells migrated to the edge of ischemic injury. A small number of cells can survive and differentiate into mature neurons or astrocytes. Mild hypothermia after ischemia can inhibit the excessive release of amino acids and monoamine neurotransmitters, and inflammatory response, but it is not known whether it regulates the proliferation and migration of neural precursor cells after ischemia. In this study, the effects of delayed mild hypothermia after ischemia on cerebral infarction size and neural function recovery were investigated, and the effects of delayed mild hypothermia on cell proliferation and differentiation after cerebral ischemia were studied. Methods: the focal cerebral ischemia-reperfusion model was established. 15mmin decreased the central temperature to 30 鈩，

本文編號(hào)：1823977