本文選題：精神分裂癥　切入點(diǎn)：BDNF　出處：《南京醫(yī)科大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：從BDNF基因rs6265多態(tài)性及外周血BDNF基因mRNA表達(dá)兩方面探究BDNF基因是否參與了精神分裂癥的發(fā)病機(jī)制；并通過分析精神分裂癥患者外周血中miR-124-3p, miR-206, miR-132的表達(dá),來初步探討B(tài)DNF參與精神分裂癥潛在的分子調(diào)控機(jī)制；探討精神分裂癥的生物學(xué)標(biāo)志與抗精神病藥物治療靶點(diǎn)。方法：本研究分為兩部分試驗(yàn),采用病例-對(duì)照研究。第一部分研究對(duì)象取自全基因組關(guān)聯(lián)分析樣本庫(包括精神分裂癥患者1407例,正常對(duì)照組1136例),利用SHE. sis軟件,用擬合度χ2檢驗(yàn)比較精神分裂癥組與正常對(duì)照組之間BDNF基因rs6265多態(tài)性的基因型分布與等位基因頻率分布。第二部分研究共收集符合入組標(biāo)準(zhǔn)的精神分裂癥患者32例,正常健康樣本48例,抽取所有樣本外周靜脈血5m1,利用反轉(zhuǎn)錄實(shí)時(shí)定量聚合酶連反應(yīng)(RT-qPCR)方法測(cè)定兩組樣本BDNF, miR-124-3p, miR-206, miR-132的mRNA表達(dá)水平。對(duì)精神分裂癥組進(jìn)行PANSS量表評(píng)估,然后對(duì)所有精神分裂癥患者進(jìn)行單一抗精神病藥物治療,隨訪服用抗精神病藥物12周后的精神分裂癥患者,再次對(duì)其進(jìn)行PANSS量表評(píng)定,然后收集樣本外周靜脈血,測(cè)定服藥12周后精神分裂癥患者BDNF,miR-124-3p, miR-206, miR-132的mRNA表達(dá)水平。本部分研究數(shù)據(jù)分析利用R軟件,用t檢驗(yàn)分析比較精神分裂癥組與正常對(duì)照組,精神分裂癥組與藥物治療組,以及藥物組與正常對(duì)照組之間的表達(dá)水平差異。結(jié)果：1.基因表達(dá)研究樣本的人口學(xué)特征無統(tǒng)計(jì)學(xué)差異(P0.05)。2. BDNF基因rs6265多態(tài)性基因型分布符合Hardy-Weinberg遺傳平衡,精神分裂癥組與正常對(duì)照組相比,rs6265多態(tài)性等位基因頻率存在統(tǒng)計(jì)學(xué)差異(P=0.037)進(jìn)一步進(jìn)行性別分層,男性樣本中基因型頻率與等位基因頻率存在統(tǒng)計(jì)學(xué)差異(P=0.009,P=0.003)。3.精神分裂癥組與正常對(duì)照組兩組外周血BDNF基因及miR-124-3p表達(dá)數(shù)據(jù)存在統(tǒng)計(jì)學(xué)差異(P=5.169e-05, P=5.241e-05),精神分裂癥患者外周血中BDNF基因mRNA表達(dá)量顯著減少,miR-124-3p表達(dá)量增多。另外兩條miRNA(miR-206,miR-132)在兩組樣本中并未發(fā)現(xiàn)統(tǒng)計(jì)學(xué)差異(P=0.114,P=0.307)。4.經(jīng)過抗精神病藥物治療12周后,精神分裂癥患者經(jīng)過PANSS量表評(píng)估,與基線水平相比,陰性癥狀與陽性癥狀都有了有效改善。(P0.05)5.服用抗精神病藥物治療后的患者與治療前的基線水平相比,BDNF表達(dá)水平上調(diào)(P=1.874e-04),miR-124-3p的表達(dá)水平下調(diào)(P=0.016)。而且藥物組BDNF與miR-124-3p的表達(dá)水平與正常對(duì)照組相比無統(tǒng)計(jì)學(xué)差異(P=0.719,P=0.183)。6.經(jīng)抗精神病藥物治療的患者與治療前的基線水平相比, miR-206,miR-132表達(dá)水平下調(diào)(P=2.863e-04,P=0.009)結(jié)論：1.BDNF基因rs6265多態(tài)性可能與中國漢族精神分裂癥有一定相關(guān)性,尤其是在男性人群中。2. BDNF基因mRNA表達(dá)可能參與了精神分裂癥的發(fā)病機(jī)制。BDNF基因可以作為精神分裂癥診斷的候選生物學(xué)標(biāo)志物和精神分裂癥潛在的治療靶點(diǎn)。3. miR-124-3p可以作為BDNF基因表達(dá)參與精神分裂癥調(diào)控機(jī)制的強(qiáng)有力的預(yù)測(cè)因子。4.miR-206與miR-132表達(dá)可能未參與精神分裂癥的發(fā)病機(jī)制。它們經(jīng)過抗精神病藥物治療后的表達(dá)水平發(fā)生變化可能與BDNF基因表達(dá)水平變化原因無關(guān)。
[Abstract]:Objective: from the mRNA BDNF gene BDNF gene rs6265 polymorphism and expression of peripheral blood in two aspects to explore the pathogenesis of the BDNF gene is involved in schizophrenia and schizophrenia; through the analysis of miR-124-3p in peripheral blood of the patients with miR-206, the expression of miR-132, to investigate BDNF in schizophrenia molecular potential disease control mechanism; to explore the biomarker of schizophrenia and antipsychotic drug targets. Methods: This study is divided into two parts: test, a case-control study. The first part of the research object from genome-wide association analysis samples (including 1407 schizophrenic patients, 1136 cases of normal control group), using SHE. SIS software. With the chi square test to compare the fitting degree between the 2 schizophrenia group and normal control group genotype BDNF gene rs6265 polymorphism distribution and allele frequency distribution. The second part of the total collection In line with the 32 cases of schizophrenic patients group spirit, healthy 48 samples collected from all samples of peripheral venous blood 5m1, even using real time quantitative reverse transcription polymerase reaction (RT-qPCR) method for the determination of two samples of BDNF, miR-124-3p, miR-206, miR-132 mRNA expression level. The schizophrenia group PANSS table of assessment, then all schizophrenia patients were single antipsychotic treatment, follow-up of antipsychotic drugs after 12 weeks of schizophrenic patients were again PANSS scale on it, then collect samples of peripheral blood were measured after 12 weeks of therapy in patients with schizophrenia, BDNF, miR-124-3p, miR-206 the expression level of miR-132 and mRNA. The part of data analysis using R software, using t test analysis of schizophrenia group and normal control group, schizophrenia group and drug treatment group, and drug group and normal The expression difference between the control group. Results: 1. gene expression in demographic characteristics of the study sample. There were no significant differences in the distribution of.2. (P0.05) BDNF gene rs6265 polymorphisms with Hardy-Weinberg genetic equilibrium, the schizophrenia group compared with normal control group, there was significant difference in rs6265 allele frequency (P=0.037) further gender there was a significant difference between the genotype stratification, male sample frequency and allele frequency (P=0.009, P=0.003).3. schizophrenia group and normal control group two group of peripheral blood BDNF gene expression of miR-124-3p and there was a significant difference between the data (P=5.169e-05, P=5.241e-05), patients with schizophrenia BDNF gene in peripheral blood mRNA expression significantly reduced expression of miR-124-3p increased. The other two miRNA (miR-206, miR-132) did not find statistical differences in the two groups (P=0.114, P=0.307) by.4. Antipsychotic medication after 12 weeks of treatment, patients with schizophrenia by PANSS were evaluated, compared with baseline, negative and positive symptoms have been effectively improved. (P0.05) compared to the baseline level 5. antipsychotic drugs patients after the treatment and before treatment, up regulate the expression level of BDNF (P=1.874e-04), the expression level of miR-124-3p decreased (P=0.016). And the expression level of BDNF and miR-124-3p of the drug group compared with the normal control group showed no significant difference (P=0.719, P=0.183).6. after baseline in patients treated with antipsychotic treatment than before, miR-206, miR-132 expression (P=2.863e-04, P=0.009) conclusion: 1.BDNF gene rs6265 polymorphism may be associated with China schizophrenia, especially in males in the.2. BDNF mRNA gene expression.BDNF gene may be involved in the pathogenesis of schizophrenia can be As a diagnosis of schizophrenia candidate biomarkers for schizophrenia and potential therapeutic targets in.3. miR-124-3p can be used as the expression of BDNF gene in schizophrenia is a strong predictor of the regulation mechanism of.4.miR-206 and miR-132 expression may not participate in the pathogenesis of schizophrenia. Unrelated to their expression level after antipsychotic drugs after treatment the change may be related to the expression level of BDNF gene changes.

【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R749.3

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本文編號(hào)：1646190