本文選題：缺血預(yù)處理 + 腦缺血耐受�。� 參考：《北京協(xié)和醫(yī)學(xué)院》2009年博士論文

【摘要】：背景和目的：腦缺血耐受是指腦組織在經(jīng)過預(yù)處理以后,獲得了抵抗嚴(yán)重缺血的能力。HIF-1α是腦缺血耐受過程中的重要轉(zhuǎn)錄因子,涉及多種基因的表達(dá)調(diào)控。miRNA是近年來發(fā)現(xiàn)的一類21-23個(gè)核苷酸的非編碼小RNA分子,在轉(zhuǎn)錄后水平上調(diào)控目標(biāo)基因的表達(dá)。研究表明,在心肌細(xì)胞內(nèi),低氧預(yù)處理誘導(dǎo)HIF-1α的表達(dá)上調(diào),且依賴于miR-199a的表達(dá)下調(diào)。本研究的目的是用小劑量3-硝基丙酸(3-NPA)預(yù)處理建立大鼠腦缺血耐受模型,探究大鼠腦缺血耐受過程中miR-199a的表達(dá)。 實(shí)驗(yàn)方法：1、建立大鼠腦缺血耐受模型：大鼠隨機(jī)分為2組,分別經(jīng)腹腔注射3-NPA或生理鹽水,3天后實(shí)施MCAO手術(shù),術(shù)后第2天測(cè)定2組大鼠的腦梗死體積,并進(jìn)行雙側(cè)t檢驗(yàn)比較分析。2、檢測(cè)miR-199a和HIF-1α在大鼠腦缺血耐受過程中的表達(dá)：大鼠隨機(jī)分為4組,分別接受生理鹽水腹腔注射、3-NPA腹腔注射、生理鹽水腹腔注射+MCAO手術(shù)和3-NPA腹腔注射+MCAO手術(shù)。第4天同時(shí)處死,取腦皮質(zhì)標(biāo)本,用實(shí)時(shí)定量PCR法檢測(cè)miR-199a和HIF-1α mRNA的水平,并進(jìn)行雙側(cè)t檢驗(yàn)比較分析。 實(shí)驗(yàn)結(jié)果：1、3-NPA組大鼠的腦梗死體積(245.43±25.24mm3)相比對(duì)照組的(313.67±26.29mm3)下降21.76%,具有統(tǒng)計(jì)學(xué)顯著性差異(p=0.003)。2、3-NPA組miR-199a的相對(duì)表達(dá)量(1.20±0.55)相比對(duì)照組(3.39±0.78)下降64.3%。3-NPA處理+MCAO組和MCAO組miR-199a的相對(duì)表達(dá)量較正常對(duì)照組無顯著差異。各組HIF-1α mRNA水平無顯著差異。 實(shí)驗(yàn)結(jié)論：在大鼠腦缺血耐受過程中,miR-199a在腦皮質(zhì)的表達(dá)水平明顯下調(diào),它與HIF-1α表達(dá)的相關(guān)性有待進(jìn)一步研究。
[Abstract]:Background and objective: cerebral ischemic tolerance is the ability of brain tissue to resist severe ischemia after pretreatment. HIF-1 偽 is an important transcription factor in the process of cerebral ischemic tolerance. MiRNAs involved in the regulation of the expression of multiple genes are a class of non-coding small RNA molecules with 21-23 nucleotides found in recent years, which regulate the expression of target genes at the post-transcriptional level. The results showed that hypoxia preconditioning induced the up-regulation of HIF-1 偽 expression in cardiomyocytes and was dependent on the down-regulation of miR-199a expression. The aim of this study was to establish a rat model of cerebral ischemic tolerance by preconditioning with low dose 3-nitropropionate (3-NPA), and to investigate the expression of miR-199a during cerebral ischemia tolerance in rats. Methods: the model of cerebral ischemia tolerance was established in rats. Rats were randomly divided into two groups. The rats were treated with MCAO after intraperitoneal injection of 3-NPA or saline for 3 days. The infarct volume of the rats in the two groups was measured on the second day after operation. The expression of miR-199a and HIF-1 偽 during cerebral ischemic tolerance in rats was detected by bilateral t test. The rats were randomly divided into 4 groups and received saline intraperitoneal injection of 3-NPA intraperitoneally respectively. Normal saline intraperitoneal injection of MCAO operation and 3-NPA intraperitoneal injection of MCAO operation. On the 4th day, the cortical samples were taken and the levels of miR-199a and HIF-1 偽 mRNA were detected by real-time quantitative PCR, and the results were compared with those of bilateral t-test. Results compared with control group, the infarct volume of rats in the 1: 1 + 3-NPA group (245.43 鹵25.24mm3) decreased by 21.76mm), and the relative expression of miR-199a in the MCAO group and MCAO group was significantly lower than that in the control group (1.20 鹵0.55). The relative expression of miR-199a in MCAO group and MCAO group was significantly lower than that in the control group (3.39 鹵0.78), and the relative expression of miR-199a in the MCAO group and MCAO group was significantly lower than that in the control group (P < 0.05), and the relative expression of miR-199a in the MCAO group and the MCAO group was significantly lower than that in the control group (P < 0.05). There was no significant difference in normal control group. There was no significant difference in the level of HIF-1 偽 mRNA in each group. Conclusion: the expression of miR-199a in cerebral cortex is down-regulated during the course of cerebral ischemia tolerance in rats. The correlation between the expression of miR-199a and the expression of HIF-1 偽 needs further study.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2009
【分類號(hào)】：R741;R3411

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相關(guān)期刊論文 前1條

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本文編號(hào)：1943021