短暫性腦缺血發(fā)作患者血清microRNA的水平變化及其臨床意義
發(fā)布時間：2018-08-17 16:11
【摘要】：短暫性腦缺血性發(fā)作(transient ischemic attacks,TIA)是指由多種原因引發(fā)局灶性腦缺血,進(jìn)而導(dǎo)致的突發(fā)性、短暫性、可逆性神經(jīng)功能障礙。TIA易反復(fù)發(fā)作,既往有一過性TIA病史的患者再次發(fā)生腦卒中的風(fēng)險明顯增加,致殘率、病死率更高。血清微小核糖核酸(microRNAs,miRNAs)是近年來的研究熱點,與缺血性腦血管疾病的發(fā)生、發(fā)展密切相關(guān),但有關(guān)TIA患者血清miRNAs表達(dá)水平及其變化尚缺乏系統(tǒng)性的研究,血清miRNAs對TIA預(yù)測及TIA后再發(fā)卒中風(fēng)險評估的臨床價值仍有待進(jìn)一步研究探討。目的:通過分析TIA患者血清miRNAs水平變化,篩選TIA患者血清特異變化的miRNAs,比較并探討血清miRNAs及現(xiàn)有腦損傷相關(guān)血清學(xué)標(biāo)志物,對TIA預(yù)測及TIA后再發(fā)卒中風(fēng)險評估的臨床價值,以期為臨床TIA患者的病情評估與監(jiān)測提供新的途徑與理論依據(jù)。方法:選取126例TIA患者和44例對照者,依據(jù)TIA患者再發(fā)卒中風(fēng)險評估體系A(chǔ)BCD3-I評分,將其分為低危(0～3分,46例)、中危(4～7分,45例)、高危(8～13 分,35 例)三組。采用實時熒光定量 PCR(quantitative reverse-transcription PCR,qRT-PCR)技術(shù),檢測候選的13種與缺血性腦血管疾病相關(guān)的miRNAs,在TIA患者和對照者血清中的相對表達(dá)水平(包括miR-15b、miR-30a、miR-21、miR-29b、miR-181 a、miR-124、miR-335、miR-146a、miR-499、miR-144、miR-208b、miR-215和miR-23b),以篩選TIA患者血清特異變化的miRNAs。同時,檢測TIA患者腦損傷相關(guān)血清學(xué)標(biāo)志物的水平,包括血清脂蛋白相關(guān)磷脂酶A2(Lipoprotein-associated phospholipase A2,Lp-PLA2)、氧化低密度脂蛋白(Oxidized low-density lipoprotein,ox-LDL)、神經(jīng)元特異性烯醇化酶(Neuron-Specific Enolase,NSE)和腦源性神經(jīng)營養(yǎng)因子(Brain Derived Neurotrophic Factor,BDNF)。采用 Spearman 相關(guān)性分析,探討血清 miRNAs 和腦損傷相關(guān)血清學(xué)標(biāo)志物之間的相關(guān)性。采用受試者工作曲線(receiver operating characteristic curves,ROC)分析和多元 Logistic 回歸分析,比較并探討血清miRNAs及腦損傷相關(guān)血清學(xué)標(biāo)志物應(yīng)用于TIA預(yù)測及TIA后再發(fā)卒中風(fēng)險評估的臨床價值。結(jié)果:一、qRT-PCR 結(jié)果顯示,TIA 患者組血清 miR-23b-3p、miR-208b、miR-215、miR-181a-5p水平較對照組均顯著升高(P均0.05);TIA患者中,高危組、中危組、低危組的血清 miR-23b-3p、miR-208b、miR-215、miR-181a-5p 水平也較對照組均顯著升高(P均0.05)。相關(guān)性分析顯示,上述四種miRNAs水平兩兩之間均呈顯著正相關(guān)(P均0.05)。二、TIA患者組血清Lp-PLA2、ox-LDL及NSE水平較對照組均顯著升高(P均0.05);TIA患者中,僅高危組患者血清Lp-PLA2、ox-LDL及NSE水平較對照組顯著升高(P均0.05)。相關(guān)性分析顯示,血清Lp-PLA2與ox-LDL水平呈顯著正相關(guān)(r= 0.264,P=0.002)、NSE與BDNF水平呈顯著正相關(guān)(r=0.197,P=0.041)。三、ROC曲線分析結(jié)果顯示,血清miR-23b-3p、miR-208b、miR-215和miR-181a-5p區(qū)分TIA患者與對照者的曲線下面積(area under the curve,AUC)分別為 0.784、0.795、0.768 和 0.779(P 均0.01),四種 miRNAs 的組合區(qū)分 TIA患者與對照者的AUC為0.812(P=0.001);血清Lp-PLA2和NSE區(qū)分TIA患者的AUC分別為0.725和0.743(P均0.05),兩指標(biāo)的組合區(qū)分TIA患者與對照者的AUC為0.817(P=0.001);四種miRNAs聯(lián)合Lp-PLA2和NSE的組合區(qū)分TIA患者與對照者的AUC為0.925(P0.001)。四、以TIA患者不同危險分層組及對照組作為獨立的四分類變量,以對照組作為參照類別,分別對血清miRNAs和腦損傷相關(guān)指標(biāo)進(jìn)行多元Logistic回歸分析。單因素Logistic回歸分析結(jié)果顯示,血清高miR-23b-3p、miR-208b、miR-215水平均與TIA患者發(fā)生卒中的各層風(fēng)險相關(guān);血清高Lp-PLA2、ox-LDL、NSE及BDNF水平均與TIA患者發(fā)生卒中的高風(fēng)險相關(guān),高NSE水平還與TIA患者發(fā)生卒中的中、低風(fēng)險相關(guān)。多因素Logistic回歸分析結(jié)果顯示,在調(diào)整年齡、性別、血壓和血脂參數(shù)的影響后,血清miR-23b-3p水平的升高仍與TIA患者發(fā)生卒中的高、中風(fēng)險密切相關(guān),miR-208b水平的升高仍與TIA患者發(fā)生卒中的高風(fēng)險密切相關(guān);血清Lp-PLA2、ox-LDL及NSE水平的升高仍與TIA患者發(fā)生卒中的高風(fēng)險密切相關(guān),Lp-PLA2、NSE水平的升高仍與TIA患者發(fā)生卒中的中、低風(fēng)險密切相關(guān)。結(jié)論:TIA 患者血清 miR-23b-3p、miR-181a-5p、miR-208b 及 miR-215 水平顯著增加,上述miRNAs有望成為TIA預(yù)測及TIA后卒中風(fēng)險評估的新型生物標(biāo)志物,為臨床TIA患者的病情評估與監(jiān)測提供新的途徑與理論依據(jù)。
[Abstract]:Transient ischemic attacks (TIA) refers to sudden, transient, reversible neurological dysfunction caused by focal cerebral ischemia caused by a variety of reasons. TIA is prone to recurrence. Patients with a history of transient TIA have a significantly increased risk of stroke recurrence, disability rate, and higher mortality. MicroRNAs (microRNAs) are the hotspots of research in recent years. They are closely related to the occurrence and development of ischemic cerebrovascular diseases. However, there is no systematic study on the expression and changes of serum microRNAs in TIA patients. The clinical value of serum microRNAs in predicting TIA and assessing the risk of recurrent stroke after TIA remains to be further studied. Objective: To analyze the changes of serum microRNAs levels in patients with TIA, screen serum microRNAs with specific changes, compare and explore the clinical value of serum microRNAs and existing serum markers related to brain injury in predicting TIA and assessing the risk of recurrent stroke after TIA, so as to provide a new way for clinical evaluation and monitoring of TIA patients. Methods: 126 TIA patients and 44 controls were divided into three groups according to the ABCD3-I score of TIA patients with recurrent stroke: low-risk group (0-3 points, 46 cases), medium-risk group (4-7 points, 45 cases) and high-risk group (8-13 points, 35 cases). The relative expression levels of 13 candidate microRNAs associated with ischemic cerebrovascular diseases (including microRNAs-15b, microRNAs-30a, microRNAs-21, microRNAs-29b, microRNAs-181a, microRNAs-124, microRNAs-335, microRNAs-146a, microRNAs-499, microRNAs-144, microRNAs-208b, microRNAs-215 and microRNAs-23b) in TIA patients and controls were measured to screen for serum-specific changes in microRNAs. Levels of serum biomarkers associated with brain injury, including Lipoprotein-associated phospholipase A2 (Lp-PLA2), oxidized low-density lipoprotein (ox-LDL), neuron-specific enolase (NSE) and brain-derived neurotrophic factor (Brain Der) Ived Neurotrophic Factor, BDNF. Spearman correlation analysis was used to explore the correlation between serum microRNAs and serum markers associated with brain injury. receiver operating characteristic curves (ROC) analysis and multiple logistic regression analysis were used to compare and explore serum microRNAs and brain injury related blood. Results: QRT-PCR results showed that serum levels of microRNAs-23b-3p, microRNAs-208 b, microRNAs-215, microRNAs-181a-5p in TIA patients were significantly higher than those in control group (all P 0.05); serum levels of microRNAs-23b-3p, microRNAs-208 b, microRNAs-215, and microRNAs-181a-5p in high-risk group, middle-risk group and low-risk group were significantly higher than those in TIA patients (all P 0.05). The levels of serum Lp-PLA2, ox-LDL and NSE in TIA patients were significantly higher than those in control group (all P 0.05). In TIA patients, the levels of serum Lp-PLA2, ox-LDL and NSE in high-risk group were higher than those in control group (all P 0.05). Correlation analysis showed that serum Lp-PLA2 and ox-LDL levels were positively correlated (r = 0.264, P = 0.002), NSE and BDNF levels were positively correlated (r = 0.197, P = 0.041). 3. ROC curve analysis showed that serum microRNA23b-3p, microRNA208b, microRNATI-215 and microRNA181a-5p could distinguish the area under the curve between A patients and controls (are A under the curve, AUC were 0.784, 0.795, 0.768 and 0.779 respectively (P 0.01). The combination of four microRNAs distinguished AUC between TIA patients and controls was 0.812 (P = 0.001); serum Lp-PLA2 and NSE distinguished AUC between TIA patients and controls was 0.725 and 0.743 (P 0.05), and the combination of the two indicators distinguished AUC between TIA patients and controls was 0.817 (P = 0.001). The AUC of TIA patients and controls was 0.925 (P 0.001). Fourth, the risk stratification group and control group of TIA patients were used as independent four classified variables. The control group was used as control group. Multiple logistic regression analysis was performed for serum microRNAs and brain injury related indicators. The results showed that high levels of serum microRNAs-23b-3p, microRNAs-208b, and microRNAs-215 were associated with the risk of stroke in TIA patients; high levels of serum Lp-PLA2, ox-LDL, NSE and BDNF were associated with high risk of stroke in TIA patients; high levels of NSE were also associated with moderate and low risk of stroke in TIA patients. After adjusting for the effects of age, sex, blood pressure and lipid parameters, the increase of serum microRNAs-23b-3p levels was still closely related to the high and moderate risk of stroke in TIA patients, the increase of microRNAs-208b levels was still closely related to the high risk of stroke in TIA patients, and the elevation of serum Lp-PLA2, ox-LDL and NSE levels was still closely related to the high risk of stroke in TIA patients. Conclusion: Serum levels of microRNAs - 23B - 3p, microRNAs - 181a - 5p, microRNAs - 208b and microRNAs - 215 in TIA patients are significantly increased. These microRNAs may be new biomarkers for predicting TIA and assessing the risk of stroke after TIA. And provide new ways and theoretical basis for monitoring.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R743.31
本文編號：2188185
[Abstract]:Transient ischemic attacks (TIA) refers to sudden, transient, reversible neurological dysfunction caused by focal cerebral ischemia caused by a variety of reasons. TIA is prone to recurrence. Patients with a history of transient TIA have a significantly increased risk of stroke recurrence, disability rate, and higher mortality. MicroRNAs (microRNAs) are the hotspots of research in recent years. They are closely related to the occurrence and development of ischemic cerebrovascular diseases. However, there is no systematic study on the expression and changes of serum microRNAs in TIA patients. The clinical value of serum microRNAs in predicting TIA and assessing the risk of recurrent stroke after TIA remains to be further studied. Objective: To analyze the changes of serum microRNAs levels in patients with TIA, screen serum microRNAs with specific changes, compare and explore the clinical value of serum microRNAs and existing serum markers related to brain injury in predicting TIA and assessing the risk of recurrent stroke after TIA, so as to provide a new way for clinical evaluation and monitoring of TIA patients. Methods: 126 TIA patients and 44 controls were divided into three groups according to the ABCD3-I score of TIA patients with recurrent stroke: low-risk group (0-3 points, 46 cases), medium-risk group (4-7 points, 45 cases) and high-risk group (8-13 points, 35 cases). The relative expression levels of 13 candidate microRNAs associated with ischemic cerebrovascular diseases (including microRNAs-15b, microRNAs-30a, microRNAs-21, microRNAs-29b, microRNAs-181a, microRNAs-124, microRNAs-335, microRNAs-146a, microRNAs-499, microRNAs-144, microRNAs-208b, microRNAs-215 and microRNAs-23b) in TIA patients and controls were measured to screen for serum-specific changes in microRNAs. Levels of serum biomarkers associated with brain injury, including Lipoprotein-associated phospholipase A2 (Lp-PLA2), oxidized low-density lipoprotein (ox-LDL), neuron-specific enolase (NSE) and brain-derived neurotrophic factor (Brain Der) Ived Neurotrophic Factor, BDNF. Spearman correlation analysis was used to explore the correlation between serum microRNAs and serum markers associated with brain injury. receiver operating characteristic curves (ROC) analysis and multiple logistic regression analysis were used to compare and explore serum microRNAs and brain injury related blood. Results: QRT-PCR results showed that serum levels of microRNAs-23b-3p, microRNAs-208 b, microRNAs-215, microRNAs-181a-5p in TIA patients were significantly higher than those in control group (all P 0.05); serum levels of microRNAs-23b-3p, microRNAs-208 b, microRNAs-215, and microRNAs-181a-5p in high-risk group, middle-risk group and low-risk group were significantly higher than those in TIA patients (all P 0.05). The levels of serum Lp-PLA2, ox-LDL and NSE in TIA patients were significantly higher than those in control group (all P 0.05). In TIA patients, the levels of serum Lp-PLA2, ox-LDL and NSE in high-risk group were higher than those in control group (all P 0.05). Correlation analysis showed that serum Lp-PLA2 and ox-LDL levels were positively correlated (r = 0.264, P = 0.002), NSE and BDNF levels were positively correlated (r = 0.197, P = 0.041). 3. ROC curve analysis showed that serum microRNA23b-3p, microRNA208b, microRNATI-215 and microRNA181a-5p could distinguish the area under the curve between A patients and controls (are A under the curve, AUC were 0.784, 0.795, 0.768 and 0.779 respectively (P 0.01). The combination of four microRNAs distinguished AUC between TIA patients and controls was 0.812 (P = 0.001); serum Lp-PLA2 and NSE distinguished AUC between TIA patients and controls was 0.725 and 0.743 (P 0.05), and the combination of the two indicators distinguished AUC between TIA patients and controls was 0.817 (P = 0.001). The AUC of TIA patients and controls was 0.925 (P 0.001). Fourth, the risk stratification group and control group of TIA patients were used as independent four classified variables. The control group was used as control group. Multiple logistic regression analysis was performed for serum microRNAs and brain injury related indicators. The results showed that high levels of serum microRNAs-23b-3p, microRNAs-208b, and microRNAs-215 were associated with the risk of stroke in TIA patients; high levels of serum Lp-PLA2, ox-LDL, NSE and BDNF were associated with high risk of stroke in TIA patients; high levels of NSE were also associated with moderate and low risk of stroke in TIA patients. After adjusting for the effects of age, sex, blood pressure and lipid parameters, the increase of serum microRNAs-23b-3p levels was still closely related to the high and moderate risk of stroke in TIA patients, the increase of microRNAs-208b levels was still closely related to the high risk of stroke in TIA patients, and the elevation of serum Lp-PLA2, ox-LDL and NSE levels was still closely related to the high risk of stroke in TIA patients. Conclusion: Serum levels of microRNAs - 23B - 3p, microRNAs - 181a - 5p, microRNAs - 208b and microRNAs - 215 in TIA patients are significantly increased. These microRNAs may be new biomarkers for predicting TIA and assessing the risk of stroke after TIA. And provide new ways and theoretical basis for monitoring.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R743.31
【參考文獻(xiàn)】
相關(guān)期刊論文 前6條
1 李睿;陳克研;金玉玲;;miRNA-29調(diào)節(jié)Wistar大鼠腦缺血再灌注損傷的研究[J];黑龍江醫(yī)藥科學(xué);2016年03期
2 馮長州;姚瀚鑫;馮玉潔;劉延青;孫淑艷;;急性冠脈綜合征患者血清IMARs與總抗氧化能力、超氧化物歧化酶的相關(guān)性[J];臨床檢驗雜志;2014年09期
3 許光;;急性腦梗死患者血清脂蛋白相關(guān)性磷脂酶A2水平的變化及意義[J];中國實用神經(jīng)疾病雜志;2013年21期
4 陶瑾;李素芳;徐明;;MicroRNA:新的心血管疾病生物標(biāo)志物[J];生理科學(xué)進(jìn)展;2011年05期
5 Maria-Giulia Perrelli;Pasquale Pagliaro;Claudia Penna;;Ischemia/reperfusion injury and cardioprotective mechanisms:Role of mitochondria and reactive oxygen species[J];World Journal of Cardiology;2011年06期
6 李立新,徐啟武,吳幼章,胡衛(wèi)星,顧培元,傅震;Combined therapy of methylprednisolone and brain-derived neurotrophic factor promotes axonal regeneration and functional recovery after spinal cord injury in rats[J];Chinese Medical Journal;2003年03期
相關(guān)碩士學(xué)位論文 前1條
1 李麗詩;高性能miRNA芯片技術(shù)SHUT assay平臺特異性研究[D];廣西師范大學(xué);2013年
，本文編號：2188185
本文鏈接：http://sikaile.net/yixuelunwen/shenjingyixue/2188185.html
最近更新
教材專著
