本文選題：神經(jīng)管畸形(NTDs) + 血小板源性生長(zhǎng)因子受體　； 參考：《山西醫(yī)科大學(xué)》2005年碩士論文

【摘要】：目的 應(yīng)用全基因組表達(dá)芯片研究山西呂梁地區(qū)神經(jīng)管畸形(neural tube defects,NTDs)胚胎腦組織中狀念特異性表達(dá)基因;將差異表達(dá)基因從四氫葉酸代謝水平、基因表達(dá)調(diào)控蛋白、信號(hào)轉(zhuǎn)導(dǎo)途徑、凋亡等途徑分類;進(jìn)一步研究于神經(jīng)系統(tǒng)發(fā)育相關(guān)的血小板源性生長(zhǎng)因子受體α(platelet-derived growth factor receptor-alpha PDGFRα)及其調(diào)節(jié)因子PAX1、PAX3-FKHR、EGFR在神經(jīng)管畸形疾病中的作用機(jī)制。 方法 利用全基因組表達(dá)芯片高通量篩選出NTDs各發(fā)病階段的異常表達(dá)基因;并從生化與分子生物學(xué)的角度加以歸類,揭示出NTDs的異常基因表達(dá)譜;從中選擇出PDGFRα基因應(yīng)用半定量RT-PCR技術(shù)擴(kuò)增PDGFRα及其調(diào)節(jié)因子PAX1、PAX3-FKHR、EGFR并驗(yàn)證其改變,同時(shí)應(yīng)用免疫組化分析PDGFRα在蛋白質(zhì)水平的表達(dá)。 結(jié)果 芯片結(jié)果顯示出異常表達(dá)的基因22209個(gè),其中2倍表達(dá)增高的基因74個(gè),包括氧化磷酸化途徑中相關(guān)基因3個(gè),鋅指結(jié)構(gòu)基因7個(gè),與抗氧化谷光甘肽通路基因2個(gè),與花生四烯酸合成代謝相關(guān)的基因2個(gè),MMPs相關(guān)的基因4個(gè),G蛋白膜受體家族相關(guān)基因6個(gè)等。2倍表達(dá)降低的387個(gè),其中與核酸代謝通路相關(guān)基因8個(gè),炎癥反應(yīng)相關(guān)基因7個(gè),參與凋亡途徑的基因6個(gè),整合素家族信號(hào)系統(tǒng)相關(guān)基因2個(gè),三羧酸循環(huán)通路相關(guān)基因4個(gè),G蛋白膜受體家族相關(guān)基因9個(gè)等,PDGFRα呈2~(0.9)倍增高;半定量RT-PCR結(jié)果顯示NTDs胚胎中PDGFRα表達(dá)高于對(duì)照組(p0.01)結(jié)果顯示NTDs胚胎中其調(diào)節(jié)因子PAX1、PAX3-FKHR、EGFR表達(dá)高于對(duì)照組(p0.01),免疫組化結(jié)果顯示NTDs組PDGFRα蛋白表達(dá)高于對(duì)照組(p0.05)。 結(jié)論 基因芯片研究結(jié)果顯示NTDs腦組織與對(duì)照腦組織的基因表達(dá)譜相比存在很大差別,證明NTDs的發(fā)生和發(fā)展是一個(gè)復(fù)雜的多階段的過程,是多種相關(guān)基因表達(dá)失常所致,涉及核酸代謝、信號(hào)轉(zhuǎn)導(dǎo)、基因表達(dá)調(diào)控、凋亡等基因的異常改變;PDGFRα調(diào)節(jié)細(xì)胞的生長(zhǎng)、存活,并且對(duì)細(xì)胞的形態(tài)和細(xì)胞運(yùn)動(dòng)如細(xì)胞的分散、趨化、聚集、凋亡等有作用。PDGFRα的過度表達(dá)干擾了神經(jīng)上皮細(xì)胞正常的分化、遷移和凋亡,導(dǎo)致膜信號(hào)轉(zhuǎn)導(dǎo)系統(tǒng)紊亂,凋亡信號(hào)減弱,神經(jīng)上皮某些細(xì)胞持續(xù)生長(zhǎng)不分化(神經(jīng)膠質(zhì)、軟骨前細(xì)胞等),繼而影響正
[Abstract]:Objective to study the expression of specific genes in embryonic brain of neural tube defectsus NTDsin Lv Liang area of Shanxi province by using the whole genome expression chip, and to express the differentially expressed genes from the level of tetrahydrofolic acid metabolism and the expression of regulatory proteins. The signal transduction pathway and apoptosis pathway were classified, and the mechanism of PAX1-PAX3-FKHR-EGFR in neural tube malformation was further studied, which was related to the development of the nervous system, platelet-derived growth factor receptor-alpha PDGFR 偽) and its regulatory factor PAX1-PAX3-FKHR-EGFR. Methods the abnormal expression genes of NTDs were screened by high throughput genomic expression microarray, and the abnormal gene expression profiles of NTDs were revealed from biochemical and molecular biology. The PDGFR 偽 gene was selected to amplify PDGFR 偽 and its regulatory factor PAX1-PAX3-FKHR-EGFR by semi-quantitative RT-PCR technique. The expression of PDGFR 偽 at protein level was analyzed by immunohistochemistry. Results the microarray results showed that there were 22209 abnormal expression genes, among which 74 genes were double expressed, including 3 genes related to oxidative phosphorylation pathway, 7 genes related to zinc finger structure, and 2 genes related to antioxidation glutamate pathway. There were 4 genes related to arachidonic acid biosynthesis and 4 genes related to MMPs, and 387 genes whose expression was reduced by 2.2-fold, including 8 genes related to nucleic acid metabolism pathway and 7 genes related to inflammation. There were 6 genes involved in apoptotic pathway, 2 integrin family signal system related genes, 4 tricarboxylic acid cycle pathway related genes, and 9 G protein membrane receptor family related genes. The results of semi-quantitative RT-PCR showed that the expression of PDGFR 偽 in NTDs embryos was higher than that in control group (p0.01). The expression of PAX1-PAX3-FKHR-EGFR in NTDs embryos was higher than that in control group, and the expression of PDGFR 偽 protein in NTDs group was higher than that in control group. Conclusion the gene expression profile of NTDs brain tissue is different from that of control brain tissue, which indicates that the occurrence and development of NTDs is a complicated and multistage process, which is caused by the abnormal expression of many related genes. Abnormal changes in genes involved in nucleic acid metabolism, signal transduction, gene expression regulation, apoptosis, etc. PDGFR 偽 regulates cell growth, survival, and cell morphology and cell movement such as cell dispersion, chemotaxis and aggregation. The overexpression of PDGFR 偽 interferes with the normal differentiation, migration and apoptosis of neural epithelial cells, which leads to the disturbance of membrane signal transduction system, the weakening of apoptotic signal, and the persistent growth and undifferentiation of some cells of neural epithelium (glia, glia, glia, glia, etc.) Prechondral cells, etc., which in turn affect the positive
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：R361

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