本文選題：腦缺血 + 蛋白組學(xué)　； 參考：《華南理工大學(xué)》2015年碩士論文

【摘要】：缺血性腦卒中是死亡率最高的第三大疾病。其病理變化的信號(hào)傳導(dǎo)通路尚不明確,本文采用基于LC-MS/MS的高通量鳥(niǎo)槍法蛋白組學(xué)研究方法對(duì)局灶性腦缺血大鼠的血漿和腦組織中的蛋白進(jìn)行測(cè)定,并對(duì)涉及不同信號(hào)通路的相關(guān)蛋白進(jìn)行了鑒定和分析。此外,異甜菊醇鈉(isoteviol sodium,STVNa)被證實(shí)具有腦保護(hù)作用,我們同時(shí)研究了STVNa對(duì)上述通路變化的調(diào)控作用。研究?jī)?nèi)容主要如下:將雄性成年Sprague-Dawley大鼠分為正常組、腦缺血(MCAO)組及缺血給藥(STVNa)組,分別收集腦組織胞漿及血漿。建立基于陽(yáng)離子交換的蛋白分級(jí)方法和基于LC-MS/MS的蛋白鑒定方法。1)分析正常組與缺血組的血漿中特異性表達(dá)的蛋白。質(zhì)譜鑒定到176個(gè)只在正常組特異性表達(dá)的蛋白,和200個(gè)只在缺血組特異性表達(dá)的蛋白。進(jìn)一步對(duì)缺血組中特異性表達(dá)的蛋白進(jìn)行基因表達(dá)組織特異性分析,得到6個(gè)具有高度腦組織特異性的蛋白。2)分析正常組與缺血組的腦組織中特異性表達(dá)的蛋白。質(zhì)譜鑒定到648個(gè)只在正常組特異性表達(dá)的蛋白,和147個(gè)只在缺血組特異性表達(dá)的蛋白。進(jìn)一步對(duì)缺血組中特異性表達(dá)的蛋白進(jìn)行通路分析,發(fā)現(xiàn)大量與炎癥、細(xì)胞死亡及自我修復(fù)相關(guān)的通路。3)分析正常組、缺血組及給藥組的腦組織中鑒定到的蛋白。質(zhì)譜鑒定到279個(gè)只在給藥組中特異性表達(dá)的蛋白。通過(guò)進(jìn)一步的通路分析發(fā)現(xiàn),STVNa抑制了腦缺血后炎癥通路的增強(qiáng)和細(xì)胞生長(zhǎng)通路的降低,同時(shí)促進(jìn)碳水化合物代謝通路與脂肪酸代謝通路。結(jié)論:1)在缺血大鼠血漿中鑒定到6個(gè)具有高度腦特異性的蛋白可為腦卒中生物標(biāo)志物的篩選提供基礎(chǔ);2)腦缺血后(4h)腦組織中與炎癥、細(xì)胞凋亡、自我修復(fù)相關(guān)的通路相對(duì)活躍;3)STVNa能抑制炎癥、促進(jìn)細(xì)胞生長(zhǎng)、促進(jìn)代謝重構(gòu),在腦缺血損傷中發(fā)揮調(diào)節(jié)作用。
[Abstract]:Ischemic stroke is the third most fatal disease. The signal transduction pathway of its pathological changes is not clear. In this paper, the protein in plasma and brain tissue of rats with focal cerebral ischemia was determined by high-throughput birdshot proteomics based on LC-MS / MS. The related proteins involved in different signal pathways were identified and analyzed. In addition, sodium isoteviol sodiferol (STVNa) has been proved to have brain protective effect. We also studied the regulation of STVNa on the changes of these pathways. The main contents of the study were as follows: adult Sprague-Dawley rats were divided into normal group, cerebral ischemia (MCAO) group and ischemic administration group (STVNa). A cationic exchange based protein classification method and a LC-MS / MS protein identification method were established to analyze the specific expression of proteins in the plasma of normal and ischemic groups. A total of 176 proteins specifically expressed in normal group and 200 in ischemic group were identified by mass spectrometry. Furthermore, six proteins with high brain tissue specificity were obtained by tissue specific analysis of the specific expression of the proteins in the ischemic group and in the ischemic group. (2) the specific expression of the protein in the brain tissue of the normal group and the ischemic group was analyzed. 648 proteins were specifically expressed in normal group and 147 proteins in ischemic group were identified by mass spectrometry. A large number of pathways related to inflammation, cell death and self-repair were found to analyze the proteins identified in brain tissues of normal group, ischemic group and administration group. A total of 279 proteins were identified by mass spectrometry and expressed only in the administration group. It was found that STVNa inhibited the increase of inflammatory pathway and the decrease of cell growth pathway after cerebral ischemia, and promoted carbohydrate metabolism pathway and fatty acid metabolic pathway. Conclusion: 1) six highly brain-specific proteins were identified in the plasma of ischemic rats to provide a basis for the screening of biomarkers for stroke. 2) inflammation and apoptosis were observed in the brain tissue (4 h after cerebral ischemia). STVNa can inhibit inflammation, promote cell growth, promote metabolic remodeling, and play a regulatory role in cerebral ischemia injury.
【學(xué)位授予單位】：華南理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R743.3

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相關(guān)期刊論文 前2條

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本文編號(hào)：2108434