發(fā)布時(shí)間：2019-06-05 16:26

【摘要】：目的 調(diào)查脂蛋白(a)[Lipoprotein(a),Lp(a)]在健康人群和疾病人群水平分布情況;探尋在各類疾病中的變化原因;比較臨床常用的免疫比濁法(Immune Turbidimetric Assay,ITA)和酶聯(lián)免疫吸附法(Enzyme-Linked Immuno Sorbent Assay,ELISA)檢測(cè)Lp(a)水平的實(shí)驗(yàn)診斷價(jià)值;建立一種檢測(cè)功能性Lp(a)[Lp(a)ly~+]水平的方法;并評(píng)價(jià)Lp(a)ly~+檢測(cè)對(duì)急性心血管事件和感染性肺炎的實(shí)驗(yàn)診斷價(jià)值。同時(shí)探討Lp(a)ly~+參與疾病發(fā)生發(fā)展的機(jī)制,為深入研究Lp(a)的病理生理作用提供有用工具。 方法 利用ITA法對(duì)健康和疾病人群的Lp(a)水平做橫斷面調(diào)查,利用Excel的篩選功能和SPSS17.0的統(tǒng)計(jì)功能判斷Lp(a)的水平分布。利用ELISA法和ITA法檢測(cè)的Lp(a)水平對(duì)疾病的診斷效果進(jìn)行評(píng)價(jià)。建立間接ELISA方法,檢測(cè)功能性Lp(a)[Lp(a)ly~+],并進(jìn)行實(shí)驗(yàn)診斷效果評(píng)價(jià)。 結(jié)果 1、大樣本橫斷面統(tǒng)計(jì)發(fā)現(xiàn):所調(diào)查人群Lp(a)水平離散程度很大,從0～1743.50mg/L。疾病人群:只有心血管系統(tǒng)、泌尿系統(tǒng)和神經(jīng)系統(tǒng)疾病3組略高于健康人群組(P0.05);感染組明顯高于健康人群組(P0.05);在年齡組間差異沒有顯著性意義(P0.05)。在性別組,女性組略高于男性組(P0.05)。 2、病例回顧性研究:急性心肌梗死(AMI)組比對(duì)照組偏高(P=0.03);不穩(wěn)定型心絞痛組(UA)也略高,但無(wú)顯著性差異(P0.05)。Lp(a)≥300mg/L的心血管病組患者比300mg/L的患者差異有顯著性意義(P0.05);在心血管疾病組Lp(a)≥300mg/L是300mg/L危險(xiǎn)性的1.44倍。 3、方法學(xué)評(píng)價(jià):用ITA和ELISA兩種方法分別檢測(cè)同一人的血漿Lp(a)總質(zhì)量,ITA法比ELISA法敏感數(shù)千倍,兩種方法沒有可比性。也無(wú)監(jiān)測(cè)UA、AMI和細(xì)菌性肺炎病情變化的臨床意義(P0.05)。 4、建立檢測(cè)Lp(a)ly~+方法:該方法能有效檢測(cè)Lp(a)ly~+,其精密度高,回收試驗(yàn)在80%～90%之間;線性檢測(cè)R~2值為0.84;高濃度總膽紅素、血紅蛋白和甘油三酯對(duì)結(jié)果影響較小。 5、Lp(a)ly~+對(duì)AMI的診斷價(jià)值:利用間接ELISA方法檢測(cè)Lp(a)ly~+能有效診斷AMI的發(fā)生(ROC曲線線下面積=1)。其診斷AMI的正確率、特異度和youden指數(shù)高于肌酸激酶同工酶(Creatine Kinase MB,CK-MB)。 6、Lp(a)ly~+對(duì)急性細(xì)菌性肺炎的診斷價(jià)值:急性細(xì)菌性肺炎患者Lp(a)ly~+水平明顯高于對(duì)照組(P0.05)。治療后Lp(a)ly~+的降低率比ITA法檢測(cè)的Lp(a)要快。檢測(cè)急性細(xì)菌性肺炎患者病程中Lp(a)ly~+水平的變化,對(duì)監(jiān)測(cè)病情、指導(dǎo)治療有積極意義。 結(jié)論 1、Lp(a)可能參與動(dòng)脈粥樣硬化的形成和發(fā)展過(guò)程。 2、Lp(a)可能參與機(jī)體的抗感染和炎癥反應(yīng);可能與惡性腫瘤的發(fā)生和發(fā)展有關(guān)。 3、目前臨床上采用的檢測(cè)Lp(a)的方法存在一定的局限,不能反映機(jī)體功能性Lp(a)的病理生理作用。 4、建立功能性Lp(a)[Lp(a)ly~+]的檢測(cè)方法,其精密度高、線性范圍廣,對(duì)溶血、黃疸、脂血影響較小。 5、Lp(a)ly~+是心肌損傷時(shí)的一種急性時(shí)相蛋白,能監(jiān)測(cè)AMI的發(fā)生和發(fā)展。 6、Lp(a)ly~+是一種抗感染免疫因子,參與了細(xì)菌感染免疫應(yīng)答,對(duì)急性細(xì)菌性肺炎的診斷和病情監(jiān)測(cè)具有重要意義。 7、建立的檢測(cè)Lp(a)ly~+的方法,為深入研究Lp(a)參與動(dòng)脈粥樣硬化、抗感染、抗腫瘤轉(zhuǎn)移和調(diào)整炎癥反應(yīng)的作用機(jī)制提供有用工具。該方法尚需進(jìn)一步完善,制備Lp(a)ly~+純品和抗體,建立敏感、特異的檢測(cè)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.
【學(xué)位授予單位】：遼寧醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R363

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