本文選題：缺血性腦卒中 + 出血性腦卒中　； 參考：《泰山醫(yī)學(xué)院》2014年碩士論文

【摘要】：目的 腦卒中是嚴重影響人類健康的疾病，其發(fā)病受遺傳和外在環(huán)境等多因素的共同作用。大量流行病學(xué)調(diào)查顯示:腦血管病發(fā)病呈現(xiàn)明顯的家族聚集性，具有遺傳傾向，且遺傳因素對其發(fā)病的作用顯著。為做好家族聚集性腦卒中的診斷和防治工作，，從基因角度研究家族性腦卒中的發(fā)病機制十分必要。本課題將家族聚集性的腦卒中病人按照卒中類型進行分類，利用全基因組分析(DNA chiP)技術(shù)，根據(jù)表達量的顯著差異，篩選出與不同類型的家族聚集性腦卒中高度相關(guān)的基因，擬確定為腦卒中差異表達候選基因，在此基礎(chǔ)上，使用實時定量PCR技術(shù)進一步驗證差異表達，試圖找出與家族聚集性腦卒中發(fā)病高度相關(guān)的易感基因，并分析這些易感基因的特征，以求成為家族性腦卒中個體化防治的有力理論依據(jù)。 方法 本實驗兩個病例組選自2012年12月至2013年12月在泰山醫(yī)學(xué)院附屬醫(yī)院神經(jīng)內(nèi)科及外科住院的腦卒中病人，每個研究對象的家族內(nèi)均有包括先癥者在內(nèi)2名以上的同類型腦卒中患者，包括10位均有缺血性腦卒中家族史(缺血性腦卒中人數(shù)超過該家族患者腦卒中總數(shù)的75%)的缺血性腦卒中患者，10位有出血性腦卒中家族史(出血性腦卒中人數(shù)超過該家族患者腦卒中總數(shù)的75%)的出血性腦卒中患者。另外選取6名同期在本院健康查體無腦血管病家族史的正常者作為對照組，對照組與實驗組同民族，男女性別比例均衡，年齡相差不超過5歲，且在同一年齡組。病例組和對照組共26例。使用統(tǒng)一的調(diào)查表對選定家系的先證者以及其親屬進行調(diào)查，記錄所有研究對象的一般臨床資料，在征得所有受檢對象同意后進行采樣，采用DNA chiP技術(shù)，分別篩選出與缺血性腦卒中患者和出血性腦卒中患者高度相關(guān)的家族聚集性候選基因，在此結(jié)果的基礎(chǔ)上，利用實時定量PCR技術(shù)進一步驗證這些基因的差異表達。 結(jié)果 1、腦出血組和腦缺血組在年齡、吸煙史、飲酒史、糖尿病病史、收縮壓、舒張壓、空腹血糖、血脂水平與對照組相比較，未見統(tǒng)計學(xué)差異(P＞0.05)。 2、RXRα基因的表達量在缺血性腦卒中組較正常對照組顯著下調(diào)，且這種差異具有統(tǒng)計學(xué)意義； 3、EVL基因的表達量在缺血性腦卒中組較正常對照組顯著上調(diào)，在出血性腦卒中組較正常對照組顯著上調(diào)，且這種差異具有統(tǒng)計學(xué)意義； 4、SYK基因的表達量在缺血性腦卒中組較正常對照組顯著下調(diào)，且這種差異具有統(tǒng)計學(xué)意義；在出血性腦卒中組變化不大； 5、LCK基因的表達量在缺血性腦卒中組較正常對照組顯著下調(diào)，且這些差異具有統(tǒng)計學(xué)意義； 6、ID3基因的表達量在缺血性腦卒中組和出血性腦卒中組較正常對照組均顯著上調(diào)，且這些差異具有統(tǒng)計學(xué)意義。結(jié)論 1、腦出血組和腦缺血組在年齡、吸煙史、飲酒史、糖尿病病史、收縮壓、舒張壓、空腹血糖、血脂水平與對照組相比較，未見統(tǒng)計學(xué)差異(P㧐0.05)。 2、RXRα基因可能與缺血性腦卒中的發(fā)病有關(guān)。缺失或低表達會增加缺血性腦卒中的易患性。 3、EVL基因可能與缺血性腦卒中和出血性腦卒中的發(fā)病均有關(guān)。其表達上調(diào)會增加腦卒中的易患性。 4、SYK基因可能與缺血性腦卒中的發(fā)病有關(guān)，但是具體的關(guān)系尚不清楚。 5、LCK基因可能與缺血性腦卒中的發(fā)病有關(guān)，低表達可能會增加缺血性腦卒中的易患性。 6、ID3基因與腦卒中的發(fā)病有關(guān)，高表達會增加缺血性與出血性腦卒中的易患性。ID3基因可能為缺血性與出血性腦卒中的易感基因。
[Abstract]:objective
Cerebral apoplexy is a disease which seriously affects human health. Its incidence is affected by many factors such as heredity and external environment. A large number of epidemiological investigations show that the incidence of cerebrovascular disease shows obvious familial aggregation, hereditary tendency, and the effect of hereditary factors on the disease. It is necessary to study the pathogenesis of familial apoplexy from a gene perspective. This topic classifies stroke patients with familial aggregation according to the type of stroke, and uses DNA chiP technology to screen out genes highly related to different types of familial aggregation of stroke according to the significant difference in expression. It is proposed to be a candidate gene for differential expression of stroke. On this basis, real time quantitative PCR technique is used to further verify the differential expression, trying to find the susceptible genes associated with familial aggregation of stroke, and analyze the characteristics of these susceptible genes in order to become a powerful theoretical basis for the individualized prevention and control of familial stroke.
Method
In this study, two cases of stroke patients were selected from December 2012 to December 2013 in the Department of Neurology and surgery in Affiliated Hospital of Tai'an Medical College. There were more than 2 stroke patients in each of the subjects including 10 of the family history of ischemic stroke (the number of ischemic stroke). 10 stroke patients with hemorrhagic stroke family history (bleeding cerebral apoplexy more than 75% of the total stroke in the family) were more than 75% of the total stroke in the family. In addition, 6 patients with normal cerebral vascular disease family history in our hospital were selected as the control group. In the control group and the experimental group, the sex ratio of men and women was balanced, the difference of age was not more than 5 years old, and in the same age group, 26 cases in the case group and the control group. A unified questionnaire was used to investigate the selected family members and their relatives, to record the general clinical data of all the subjects, and to obtain the consent of all the subjects. DNA chiP technique was used to screen out the family clustered candidate genes highly related to patients with ischemic stroke and hemorrhagic stroke. On the basis of the results, the differential expression of these genes was further verified by real-time quantitative PCR technique.
Result
1, there was no statistically significant difference in age, smoking history, drinking history, diabetes history, systolic pressure, diastolic pressure, fasting blood pressure, fasting blood glucose and blood lipid level compared with the control group (P > 0.05).
2, the expression of RXR alpha gene was significantly lower in the ischemic stroke group than in the normal control group, and the difference was statistically significant.
3, the expression of EVL gene was significantly up-regulated in the ischemic stroke group than in the normal control group, and the difference was significantly higher in the hemorrhagic stroke group than in the normal control group, and the difference was statistically significant.
4, the expression of SYK gene was significantly lower in the ischemic stroke group than in the normal control group, and the difference was statistically significant, and there was no significant change in the hemorrhagic stroke group.
5, the expression of LCK gene in ischemic stroke group was significantly lower than that in normal control group, and these differences were statistically significant.
6, the expression of ID3 gene in ischemic stroke group and hemorrhagic stroke group was significantly higher than that in normal control group, and these differences were statistically significant.
1, there was no statistically significant difference in age, smoking history, drinking history, diabetes history, systolic pressure, diastolic pressure, fasting blood pressure, fasting blood glucose and blood lipid level compared with the control group (P? 0.05).
2, RXR alpha gene may be associated with ischemic stroke. Loss or low expression will increase the susceptibility of ischemic stroke.
3, the EVL gene may be associated with the onset of ischemic stroke and hemorrhagic stroke.
4, the SYK gene may be related to the pathogenesis of ischemic stroke, but the specific relationship is not yet clear.
5, the LCK gene may be associated with ischemic stroke, and low expression may increase the risk of ischemic stroke.
6, the ID3 gene is associated with the onset of stroke. High expression may increase the susceptibility of ischemic and hemorrhagic stroke to susceptible.ID3 genes, which may be susceptible genes for ischemic and hemorrhagic stroke.
【學(xué)位授予單位】：泰山醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R743.3

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