本文選題：缺血預處理 + 腦缺血耐受　； 參考：《北京協(xié)和醫(yī)學院》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)過預處理以后,獲得了抵抗嚴重缺血的能力。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調(diào)控。miRNA是近年來發(fā)現(xiàn)的一類21-23個核苷酸的非編碼小RNA分子,在轉(zhuǎn)錄后水平上調(diào)控目標基因的表達。研究表明,在心肌細胞內(nèi),低氧預處理誘導HIF-1α的表達上調(diào),且依賴于miR-199a的表達下調(diào)。本研究的目的是用小劑量3-硝基丙酸(3-NPA)預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。 實驗方法：1、建立大鼠腦缺血耐受模型：大鼠隨機分為2組,分別經(jīng)腹腔注射3-NPA或生理鹽水,3天后實施MCAO手術(shù),術(shù)后第2天測定2組大鼠的腦梗死體積,并進行雙側(cè)t檢驗比較分析。2、檢測miR-199a和HIF-1α在大鼠腦缺血耐受過程中的表達：大鼠隨機分為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天同時處死,取腦皮質(zhì)標本,用實時定量PCR法檢測miR-199a和HIF-1α mRNA的水平,并進行雙側(cè)t檢驗比較分析。 實驗結(jié)果：1、3-NPA組大鼠的腦梗死體積(245.43±25.24mm3)相比對照組的(313.67±26.29mm3)下降21.76%,具有統(tǒng)計學顯著性差異(p=0.003)。2、3-NPA組miR-199a的相對表達量(1.20±0.55)相比對照組(3.39±0.78)下降64.3%。3-NPA處理+MCAO組和MCAO組miR-199a的相對表達量較正常對照組無顯著差異。各組HIF-1α mRNA水平無顯著差異。 實驗結(jié)論：在大鼠腦缺血耐受過程中,miR-199a在腦皮質(zhì)的表達水平明顯下調(diào),它與HIF-1α表達的相關性有待進一步研究。
[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.
【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2009
【分類號】：R741;R3411

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本文編號：1943021