老年髋部骨折患者环状RNA差异表达的研究
发布时间：2018-08-03 10:44
【摘要】：髋部骨折是老年人最易发生的骨折之一,国内外很多研究都显示与同年龄正常人群相比老年髋部骨折患者的死亡率以及死亡风险都明显更高。老年髋部骨折后出现的过度全身炎性反应导引发多种器官功能损害,是导致死亡事件的独立危险因素。目前临床已经运用一些评分系统和多种生物标记物,以期更精准的评估病情以及高危风险程度,减轻器官损害程度,改善患者的预后。但目前全身炎症反应导致的多脏器功能衰竭的精准诊治及相应的机制研究仍存在一定的不足,需要进一步完善,特别是需要寻找更加可靠、特异性强、灵敏度高的生物标志物用于该领域疾病的进程监测以及治疗评价。随着对环状RNA系统深入的研究,发现其在该领域具有很强的创新与现实性意义,为临床诊疗提供了新的思路和方向。第一部分:环状RNA在老年髋部骨折患者中差异表达的研究目的:应用环状RNA芯片技术分析老年髋部骨折患者外周血血浆中环状RNA的差异表达,为老年髋部骨折后初期病情进展及后期转归预测提供的有效的生物标志物及其调控机制研究奠定基础。方法:选择符合条件的研究对象3例普通老年髋部骨折患者(实验组)、3例体检健康老年人(对照组)。分别收集研究对象外周静脉血4-5ml,分离出血浆,提取总RNA,利用circRNA芯片技术,筛查老年髋部骨折患者血浆中差异性表达的环状RNA,利用生物信息学方法预测各项差异表达的环状RNA的相关miRNA。结果:实验组和对照组根据circRNA表达水平的不同,两组之间折叠倍率(Fold Change, FC)2.0或-2.0, P0.05的有统计学差异的显著差异表达的circRNA数据。circRNA表达水平在实验组和对照组中的差异性表达相比,共得到2169种circRNA显著差异性表达,其中包括1173种表达上调,差异倍数大于5倍有213种,996种表达下调,差异倍数大于5倍有151种。生物信息学统计结果显示环状RNA可以通过与miRNA相互作用参与调控老年髋部骨折后初期病程的发展过程。结论:老年髋部骨折患者外周血血浆内环状RNA的表达较普通健康老年人具有异性,经生物信息学统计差异性表达的环状RNA有助于老年髋部骨折患者初期病情进展及后期转归预测的研究,为相应的机制研究提供有益的参考和补充。第二部分:环状RNA在老年髋部骨折后死亡患者中差异表达的研究目的:应用环状RNA芯片技术分析老年髋部骨折后死亡患者外周血血浆中环状RNA的差异表达,为进一步研究差异性表达的环状RNA作为老年髋部骨折后死亡风险评估、以及病情进展转归的生物标志物及其调控机制研究奠定基础。方法:研究对象为老年髋部骨折患者30例,其中男性12例,女性18例,经过骨折后一年的随访,3例因肺部感染死亡。3例髋部骨折后一年内死亡的患者(死亡组)、3例普通老年髋部骨折患者(对照组),分别收集研究对象外周静脉血4-5ml,分离出血浆,提取总RNA,利用circRNA芯片技术,筛查老年髋部骨折后死亡患者血浆中差异性表达的环状RNA,利用生物信息学方法预测各项差异表达的环状RNA的相关miRNA,最后对部分感兴趣的环状RNA采用实时定量PCR进行验证。结果:死亡组和对照组根据circRNA表达水平的不同,两组之间折叠倍率(Fold Change, FC)2.0或-2.0, P0.05的有统计学差异的显著差异表达的circRNA数据。circRNA表达水平在死亡组和对照组中的差异性表达相比,共得到1263种circRNA显著差异性表达,其中包括670种表达上调,差异倍数大于5倍有131种,593种表达下调,差异倍数大于5倍有119种。其中对hsa-circRNA-103637、hsa-circRNA-092417两种环状RNA经实时定量PCR验证呈上调趋势;另外3种环状 RNA: hsa-circRNA-100035、hsa-circRNA-045308、hsa-circRNA-001057 经实时定量PCR验证表达呈下调趋势,和芯片结果一致。生物信息学统计结果显示环状RNA可以通过与miRNA相互作用参与调控老年髋部骨折后导致死亡主要并发症的发生和发展过程。结论:老年髋部骨折后死亡患者外周血血浆内环状RNA的表达较普通骨折患者具有差异性,显著差异的和特异性表达的环状RNA有望成为老年髋部骨折后死亡事件发生潜在的诊断标志物。此外,经生物信息学统计差异性表达的环状RNA有助于老年髋部骨折患者死亡事件机制的研究,为机制研究提供有益的参考和补充。
[Abstract]:Hip fractures are one of the most likely fractures in the elderly. Many studies at home and abroad have shown that the mortality and death risk of hip fractures in the elderly are significantly higher than those of the normal age group. The excessive systemic inflammatory response to the elderly hip fracture leads to multiple organ dysfunction, which is the only one that causes death. At present, some scoring systems and several biomarkers have been used to evaluate the severity of the disease and the risk of risk, reduce the degree of organ damage and improve the prognosis of the patients. However, there are still some studies on the accurate diagnosis and treatment of multiple organ failure caused by systemic inflammatory response and the corresponding mechanism research. It needs further improvement, especially the need to find more reliable, specific and sensitive biomarkers for the process monitoring and treatment evaluation of the disease in this field. With the in-depth study of the circular RNA system, it is found that it has a strong innovative and practical significance in this field, and provides a new way of thinking for clinical diagnosis and treatment. Part 1: Study of differential expression of annular RNA in elderly hip fracture patients: analysis of the differential expression of ring RNA in peripheral blood plasma in elderly hip fracture patients by circular RNA chip technology, and to provide effective biomarkers and regulation for the early progression and prognosis of the elderly hip fracture. Methods: 3 cases of common elderly hip fracture (experimental group) and 3 healthy aged people (control group) were selected. The 4-5ml of peripheral venous blood was collected, the bleeding plasma was separated and the total RNA was extracted. The differential table of plasma in the elderly patients with hip fracture was screened by circRNA chip technology. The cyclic RNA of Da was used to predict the related miRNA. results of different expressions of cyclic RNA using bioinformatics methods: the experimental group and the control group based on the difference of the circRNA expression level, the two groups of folding rates (Fold Change, FC) 2 or -2.0, and the significant difference in the statistical difference expressed in P0.05, the.CircRNA expression level of the circRNA data was true Compared with the difference expression in the test group and the control group, 2169 different expressions of circRNA were obtained, including 1173 kinds of expression up regulation, the difference multiplier is more than 5 times 213, the 996 kinds of expressions are down, the difference multiple is more than 5 times 151. The bioinformatics statistics show that the ring RNA can participate in the regulation of the aged by interacting with miRNA. The development process of the initial course after hip fracture. Conclusion: the expression of annular RNA in peripheral blood plasma in elderly hip fracture patients is more heterosexual than that of normal healthy old people. The circular RNA expressed differently by bioinformatics is helpful to the study of the early progression and prognosis of the elderly hip fracture patients, which is the corresponding mechanism. The study provides useful references and supplements. The second part: the study of differential expression of annular RNA in elderly patients with hip fracture. Objective: to analyze the differential expression of cyclic RNA in peripheral blood plasma in elderly patients with hip fracture after the aged hip fracture, and to further study the differential expression of circular RNA as the elderly hip. The risk assessment of post fracture death, and the study of biomarkers and regulatory mechanisms of the progression of the disease were established. Methods: 30 elderly patients with hip fractures were studied, including 12 males and 18 females. After one year of follow-up after fracture, 3 patients died within one year of.3 cases of hip fracture due to pulmonary infection and death (death group). 3 cases of common aged hip fracture (control group) were collected, the peripheral venous blood 4-5ml was collected, the hemorrhagic pulp was separated and the total RNA was extracted. The differential expression of circular RNA in the plasma of the dead patients after the hip fracture was screened by circRNA chip technology, and the related miR related to the differential expression of annular RNA was predicted by the method of bioinformatics. NA, at last, some interesting circular RNA were verified by real time quantitative PCR. Results: the death and control groups based on the difference of the circRNA expression level, the two groups of folding rates (Fold Change, FC) 2 or -2.0, and the statistically significant difference expressed in P0.05, the.CircRNA expression of circRNA data was in the death and control groups There were 1263 different expressions of circRNA, including 670 up-regulated expressions, 131 different multiplier than 5 times, 593 down-regulation and 119 different multiplier than 5 times, of which hsa-circRNA-103637, hsa-circRNA-092417 two ring RNA showed up trend by real-time quantitative PCR verification; the other 3 rings were up. The expression of RNA: hsa-circRNA-100035, hsa-circRNA-045308, and hsa-circRNA-001057 was down regulated by real-time quantitative PCR. The results of bioinformatics statistics show that ring RNA can participate in the occurrence and development of the major complications of death and death through the interaction with miRNA in the regulation of hip fracture in the elderly. The expression of annular RNA in the peripheral blood plasma of the elderly patients with hip fracture is different from that of the common fracture patients. The significant difference and specific expression of cyclic RNA may be a potential diagnostic marker for the death events of the elderly hip fracture. Furthermore, the cyclic RNA expressed by bioinformatics statistics is helpful to the elderly. The study on the mechanism of death in patients with hip fracture in the year provides useful reference and supplement for mechanism research.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R683
本文编号：2161498
[Abstract]:Hip fractures are one of the most likely fractures in the elderly. Many studies at home and abroad have shown that the mortality and death risk of hip fractures in the elderly are significantly higher than those of the normal age group. The excessive systemic inflammatory response to the elderly hip fracture leads to multiple organ dysfunction, which is the only one that causes death. At present, some scoring systems and several biomarkers have been used to evaluate the severity of the disease and the risk of risk, reduce the degree of organ damage and improve the prognosis of the patients. However, there are still some studies on the accurate diagnosis and treatment of multiple organ failure caused by systemic inflammatory response and the corresponding mechanism research. It needs further improvement, especially the need to find more reliable, specific and sensitive biomarkers for the process monitoring and treatment evaluation of the disease in this field. With the in-depth study of the circular RNA system, it is found that it has a strong innovative and practical significance in this field, and provides a new way of thinking for clinical diagnosis and treatment. Part 1: Study of differential expression of annular RNA in elderly hip fracture patients: analysis of the differential expression of ring RNA in peripheral blood plasma in elderly hip fracture patients by circular RNA chip technology, and to provide effective biomarkers and regulation for the early progression and prognosis of the elderly hip fracture. Methods: 3 cases of common elderly hip fracture (experimental group) and 3 healthy aged people (control group) were selected. The 4-5ml of peripheral venous blood was collected, the bleeding plasma was separated and the total RNA was extracted. The differential table of plasma in the elderly patients with hip fracture was screened by circRNA chip technology. The cyclic RNA of Da was used to predict the related miRNA. results of different expressions of cyclic RNA using bioinformatics methods: the experimental group and the control group based on the difference of the circRNA expression level, the two groups of folding rates (Fold Change, FC) 2 or -2.0, and the significant difference in the statistical difference expressed in P0.05, the.CircRNA expression level of the circRNA data was true Compared with the difference expression in the test group and the control group, 2169 different expressions of circRNA were obtained, including 1173 kinds of expression up regulation, the difference multiplier is more than 5 times 213, the 996 kinds of expressions are down, the difference multiple is more than 5 times 151. The bioinformatics statistics show that the ring RNA can participate in the regulation of the aged by interacting with miRNA. The development process of the initial course after hip fracture. Conclusion: the expression of annular RNA in peripheral blood plasma in elderly hip fracture patients is more heterosexual than that of normal healthy old people. The circular RNA expressed differently by bioinformatics is helpful to the study of the early progression and prognosis of the elderly hip fracture patients, which is the corresponding mechanism. The study provides useful references and supplements. The second part: the study of differential expression of annular RNA in elderly patients with hip fracture. Objective: to analyze the differential expression of cyclic RNA in peripheral blood plasma in elderly patients with hip fracture after the aged hip fracture, and to further study the differential expression of circular RNA as the elderly hip. The risk assessment of post fracture death, and the study of biomarkers and regulatory mechanisms of the progression of the disease were established. Methods: 30 elderly patients with hip fractures were studied, including 12 males and 18 females. After one year of follow-up after fracture, 3 patients died within one year of.3 cases of hip fracture due to pulmonary infection and death (death group). 3 cases of common aged hip fracture (control group) were collected, the peripheral venous blood 4-5ml was collected, the hemorrhagic pulp was separated and the total RNA was extracted. The differential expression of circular RNA in the plasma of the dead patients after the hip fracture was screened by circRNA chip technology, and the related miR related to the differential expression of annular RNA was predicted by the method of bioinformatics. NA, at last, some interesting circular RNA were verified by real time quantitative PCR. Results: the death and control groups based on the difference of the circRNA expression level, the two groups of folding rates (Fold Change, FC) 2 or -2.0, and the statistically significant difference expressed in P0.05, the.CircRNA expression of circRNA data was in the death and control groups There were 1263 different expressions of circRNA, including 670 up-regulated expressions, 131 different multiplier than 5 times, 593 down-regulation and 119 different multiplier than 5 times, of which hsa-circRNA-103637, hsa-circRNA-092417 two ring RNA showed up trend by real-time quantitative PCR verification; the other 3 rings were up. The expression of RNA: hsa-circRNA-100035, hsa-circRNA-045308, and hsa-circRNA-001057 was down regulated by real-time quantitative PCR. The results of bioinformatics statistics show that ring RNA can participate in the occurrence and development of the major complications of death and death through the interaction with miRNA in the regulation of hip fracture in the elderly. The expression of annular RNA in the peripheral blood plasma of the elderly patients with hip fracture is different from that of the common fracture patients. The significant difference and specific expression of cyclic RNA may be a potential diagnostic marker for the death events of the elderly hip fracture. Furthermore, the cyclic RNA expressed by bioinformatics statistics is helpful to the elderly. The study on the mechanism of death in patients with hip fracture in the year provides useful reference and supplement for mechanism research.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R683
【参考文献】
相关期刊论文 前2条
1 李绍光;刘智;孙天胜;任继鑫;;老年髋部骨折术后1年死亡率及危险因素分析[J];北京医学;2015年11期
2 夏世金;高文;胡明冬;刘露梅;邰先桃;;环状RNA的研究现状及展望[J];中华肺部疾病杂志(电子版);2014年06期
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