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与多聚赖氨酸结合的脂蛋白(a)病理生理作用初步研究

发布时间:2019-06-05 16:26
【摘要】:目的 调查脂蛋白(a)[Lipoprotein(a),Lp(a)]在健康人群和疾病人群水平分布情况;探寻在各类疾病中的变化原因;比较临床常用的免疫比浊法(Immune Turbidimetric Assay,ITA)和酶联免疫吸附法(Enzyme-Linked Immuno Sorbent Assay,ELISA)检测Lp(a)水平的实验诊断价值;建立一种检测功能性Lp(a)[Lp(a)ly~+]水平的方法;并评价Lp(a)ly~+检测对急性心血管事件和感染性肺炎的实验诊断价值。同时探讨Lp(a)ly~+参与疾病发生发展的机制,为深入研究Lp(a)的病理生理作用提供有用工具。 方法 利用ITA法对健康和疾病人群的Lp(a)水平做横断面调查,利用Excel的筛选功能和SPSS17.0的统计功能判断Lp(a)的水平分布。利用ELISA法和ITA法检测的Lp(a)水平对疾病的诊断效果进行评价。建立间接ELISA方法,检测功能性Lp(a)[Lp(a)ly~+],并进行实验诊断效果评价。 结果 1、大样本横断面统计发现:所调查人群Lp(a)水平离散程度很大,从0~1743.50mg/L。疾病人群:只有心血管系统、泌尿系统和神经系统疾病3组略高于健康人群组(P0.05);感染组明显高于健康人群组(P0.05);在年龄组间差异没有显著性意义(P0.05)。在性别组,女性组略高于男性组(P0.05)。 2、病例回顾性研究:急性心肌梗死(AMI)组比对照组偏高(P=0.03);不稳定型心绞痛组(UA)也略高,但无显著性差异(P0.05)。Lp(a)≥300mg/L的心血管病组患者比300mg/L的患者差异有显著性意义(P0.05);在心血管疾病组Lp(a)≥300mg/L是300mg/L危险性的1.44倍。 3、方法学评价:用ITA和ELISA两种方法分别检测同一人的血浆Lp(a)总质量,ITA法比ELISA法敏感数千倍,两种方法没有可比性。也无监测UA、AMI和细菌性肺炎病情变化的临床意义(P0.05)。 4、建立检测Lp(a)ly~+方法:该方法能有效检测Lp(a)ly~+,其精密度高,回收试验在80%~90%之间;线性检测R~2值为0.84;高浓度总胆红素、血红蛋白和甘油三酯对结果影响较小。 5、Lp(a)ly~+对AMI的诊断价值:利用间接ELISA方法检测Lp(a)ly~+能有效诊断AMI的发生(ROC曲线线下面积=1)。其诊断AMI的正确率、特异度和youden指数高于肌酸激酶同工酶(Creatine Kinase MB,CK-MB)。 6、Lp(a)ly~+对急性细菌性肺炎的诊断价值:急性细菌性肺炎患者Lp(a)ly~+水平明显高于对照组(P0.05)。治疗后Lp(a)ly~+的降低率比ITA法检测的Lp(a)要快。检测急性细菌性肺炎患者病程中Lp(a)ly~+水平的变化,对监测病情、指导治疗有积极意义。 结论 1、Lp(a)可能参与动脉粥样硬化的形成和发展过程。 2、Lp(a)可能参与机体的抗感染和炎症反应;可能与恶性肿瘤的发生和发展有关。 3、目前临床上采用的检测Lp(a)的方法存在一定的局限,不能反映机体功能性Lp(a)的病理生理作用。 4、建立功能性Lp(a)[Lp(a)ly~+]的检测方法,其精密度高、线性范围广,对溶血、黄疸、脂血影响较小。 5、Lp(a)ly~+是心肌损伤时的一种急性时相蛋白,能监测AMI的发生和发展。 6、Lp(a)ly~+是一种抗感染免疫因子,参与了细菌感染免疫应答,对急性细菌性肺炎的诊断和病情监测具有重要意义。 7、建立的检测Lp(a)ly~+的方法,为深入研究Lp(a)参与动脉粥样硬化、抗感染、抗肿瘤转移和调整炎症反应的作用机制提供有用工具。该方法尚需进一步完善,制备Lp(a)ly~+纯品和抗体,建立敏感、特异的检测Lp(a)ly~+的方法。
[Abstract]:Purpose To investigate the distribution of lipoprotein (a)[Lippotein (a), Lp (a)] in the healthy population and the population of the disease; to explore the causes of the change in various diseases; to compare the immunoturbidimetric Assay (ITA) and the enzyme-linked immunosorbent assay (Enzyme-Linked Immuno Sorbent Asa), which are commonly used in clinical practice. The diagnostic value of Lp (a) was measured by y (ELISA), a method for detecting the level of Lp (a)[Lp (a) ly ~ +] was established, and the diagnostic value of Lp (a) ly ~ + was evaluated for acute cardiovascular events and infectious pneumonia. The mechanism of the development of Lp (a) ly ~ + involved in the development of the disease was also discussed. A tool. Methods The level of Lp (a) in health and disease population was investigated by a method of ITA, and Lp (a) was determined by using the statistical function of Excel and the statistical function of SPSS17.0. The diagnostic effect of Lp (a) level detected by ELISA and ITA method in the diagnosis of disease The fruit was evaluated. The indirect ELISA method was established to detect the functional Lp (a)[Lp (a) ly ~ +] and to carry out the experiment. cut-off Results 1. The statistical finding of large sample cross-section showed that the level of Lp (a) in the investigated population was very large, from 0 to 17. 43.50 mg/ L. The disease group: only the cardiovascular system, the urinary system and the nervous system disease group were slightly higher than those in the healthy group (P0.05); the infection group was significantly higher than that in the healthy group (P0.05); there was no significant difference between the age groups. Significance (P0.05). In the sex group, the female group was slightly higher than that of the male The patients with acute myocardial infarction (AMI) were higher (P = 0.03) than in the control group (P = 0.03). The patients with unstable angina (UA) were slightly higher, but there was no significant difference (P0.05). significance (P0.05); in the cardiovascular disease group, Lp (a) and 300 mg/ L were 300 mg / L risk 1.44 times.3. Methodological evaluation: The total mass of plasma Lp (a) of the same person was detected by ITA and ELISA, and the ITA method was more sensitive than the ELISA method. Thousands of times, the two methods were not comparable. There was no monitoring of UA, AMI, and bacterial pneumonia. The clinical significance of the detection of Lp (a) ly ~ + was established: the method can effectively detect the Lp (a) ly ~ +, its precision is high, the recovery test is between 80% and 90%, the linear detection of R ~ 2 value is 0.84, and the high concentration of total bilirubin and blood The effect of red protein and triglyceride on AMI was small. The diagnostic value of Lp (a) ly ~ + for AMI: the detection of Lp (a) ly ~ + can be effectively diagnosed by indirect ELISA. The incidence of AMI (line area under the ROC curve = 1). The correct rate, the specificity and the youden index of the AMI were higher than that of the creatine kinase (Creati). The diagnostic value of ne Kinase MB (CK-MB).6, Lp (a) ly ~ + on acute bacterial pneumonia: Lp (a) l in patients with acute bacterial pneumonia The level of y ~ + was significantly higher than that in the control group (P0.05). The reduction rate of Lp (a) is faster than that of the ITA method. Lp (a) ly ~ + in the course of acute bacterial pneumonia is detected. change Conclusion:1. Lp (a) may be involved in the formation and development of atherosclerosis. Lp (a) may be involved in the body anti-infection and inflammatory response; may be related to the occurrence and development of malignant tumor.3. The current method for detecting Lp (a) is present The functional Lp (a) (a)[Lp (a) ly ~ +] is established. The method has the advantages of high precision, wide linear range, small effect on hemolysis, yellow blood fat and blood fat, and 5, Lp (a) l Y ~ + is an acute phase protein in myocardial injury, which can monitor the occurrence and development of AMI. It is of great significance to diagnose and monitor the acute bacterial pneumonia with the immune response of bacterial infection. And provides a useful tool for the mechanism of the action of atherosclerosis, anti-infection, anti-tumor metastasis and the regulation of the inflammatory reaction.
【学位授予单位】:辽宁医学院
【学位级别】:硕士
【学位授予年份】:2011
【分类号】:R363

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