血清8-异构前列腺素变化与川崎病相关性的研究

发布时间：2018-06-17 02:16

本文选题：川崎病 + 8-异构前列腺素　；参考：《吉林大学》2012年硕士论文

【摘要】：KD是一种以全身血管炎变为主要病理特点的急性发热性出疹性小儿疾病，可病发冠状动脉损害，成为后天获得性心脏病最常见的原因。近几十年来，KD的发病率呈逐年升高趋势，虽然KD冠状动脉改变比例有所下降，但丙种球蛋白治疗无反应型KD比例升高，KD的病因及发病机制研究一直是医学家研究的热点和难点。现在的观点趋向于：外界环境及各种致病因子作用于具有遗传易感性的个体，导致机体免疫失衡，释放细胞因子、化学分子、活性氧等一系列炎症因子，引起全身非特异性的血管炎，尤其以冠状动脉为著。8-ISO-PGF2a具有化学稳定性，是过氧化反应特异的产物，能在体内形成，由于该物质的生成不需酶的参与（与环氧化酶无关），在体液中能够稳定存在，被认为是判断活体内自由基氧化强度和临床上评价抗氧化剂疗效的最理想的生化指标。近年又有研究发现血管炎、心血管系统疾病的发病与氧化损伤和抗氧化防护的失衡有关[69]。8-ISO-PGF2a具有明显的收缩血管作用[70]，且与去甲肾上腺素和血管紧张素协同促进血管收缩；刺激血管内皮细胞分化、增值；促使血小板的聚集和变形；引起成纤维细胞和心肌细胞的增殖；氧化损伤后细胞膜上酯化的8-异构前列腺素数量增多，细胞膜的完整性被破坏，流动性发生改变，从而导致细胞的结构、功能受损，甚至导致细胞死亡。研究证实8-ISO-PGF2a与冠状动脉粥样硬化、高血压、心肌肥厚、川崎病等心血管系统疾病密切相关。KD血管内皮功能障碍与氧化应激水平升高有关。其机制是机体的炎症以及损伤可以产生活性氧（ROS），ROS在低水平时，参与信号传导来调节细胞生长、细胞适应性反应等细胞功能，，当ROS过多时，它可以通过DNA损伤以及细胞信号传导、脂质过氧化反应、蛋白质变性等途径引起细胞损伤甚至坏死，促进单核巨噬细胞及淋巴细胞从血管内膜及外膜渗透迁移，导致血管全层炎症，导致内皮细胞及平滑肌细胞破坏，导致冠脉扩张。本实验选取2010年3月至2011年10月吉林大学白求恩第一医院小儿心血管科确诊川崎病的住院患儿35例为KD组，其中男21例，女14例，年龄4个月至5岁不等，平均年龄（2.35±1.52）岁，中位数为2岁。同期住院的排除KD后的发热性疾病患儿25例为发热对照组，其中男孩15例，女孩10例，平均年龄（2.27±1.65）岁。同期在我院儿科门诊进行体检排除炎症性疾病的健康儿童25例为正常对照组，男14例，女11例，平均年龄（1.98±1.45）岁，化验检查未见异常。经过酶联免疫吸附试验，检测三组患儿血清8-ISO-PGF2a素水平，通过统计学方法对结果进行分析，探讨氧化应激与KD的发病机制的关系，观察8-异构前列腺素与冠状动脉损害及丙种球蛋白治疗效果的相关性。研究结果发现KD急性期与KD恢复期、发热对照组比较血清8-ISO-PGF2a水平升高明显，且KD恢复期患儿血清8-ISO-PGF2a水平较发热对照组升高明显，差异有统计学意义。KD急性期、KD恢复期、发热对照组较正常对照组升高明显，差异有统计学意义。表明8-ISO-PGF2a为标志的氧化应激可能参与KD患儿急性期血管炎的发病机制，且在相当时间的恢复期中，有可能继续参与冠脉的损伤。急性期KD合并CAL组患儿血清8-ISO-PGF2a较NCAL组明显升高，差异有统计学意义。急性期KD冠脉扩张量和血清8-ISO-PGF2a含量呈正相关，R=0.937，P＜0.05。8-异构前列腺素水平与KD冠状动脉损伤的并发症有相关性，可能对于评估KD冠状动脉损伤发生的概率及远期预后有一定价值。IVIG无反应型KD组患儿血清8-ISO-PGF2a较IVIG敏感组相比升高显著，但P=0.05，需进一步研究。因此，8-异构前列腺素参与KD非特性血管炎的病理生理过程。其恢复期水平仍较高，有望成为评估KD冠状动脉损伤的危险度及其预后。为抗氧化剂在冠状动脉病变中的应用提供了广阔的前景。但将异构前列腺素作为治疗冠状动脉病变靶点的研究有待进一步研究。
[Abstract]:KD is an acute febrile eruptive infantile disease with systemic vasculitis as the main pathological feature, which can cause coronary artery damage and become the most common cause of acquired acquired heart disease. In recent decades, the incidence of KD is increasing year by year, although the proportion of coronary artery change in KD has declined, but the treatment of gamma globulin is not reverse. The increase in the proportion of KD, the cause and pathogenesis of KD has always been a hot and difficult point in the research of the medical family. The present view tends to be that the external environment and various pathogenic factors act on individuals with genetic susceptibility, causing immune imbalance, releasing cytokines, chemical molecules, active oxygen and other inflammatory factors and causing the whole body. Nonspecific vasculitis, especially the coronary artery, is a chemical stability of.8-ISO-PGF2a, which is a peroxidation specific product and can be formed in the body. Because the formation of the substance does not require enzyme involvement (irrelevant with cyclooxygenase), it can be stable in body fluid and is considered to be a judgement of the free radical oxidation intensity and clinical evaluation in vivo. The most ideal biochemical indicators for the efficacy of anti oxidants. Recent studies have found vasculitis, the pathogenesis of cardiovascular system diseases and the imbalance of oxidative damage and antioxidant protection. [69].8-ISO-PGF2a has an obvious vasoconstrictor effect of [70], and promotes vasoconstriction in conjunction with norepinephrine and vasotensioning; stimulates the intravascular injection. The differentiation and increment of the skin cells promote the aggregation and deformation of platelets; the proliferation of fibroblasts and cardiomyocytes; the increase in the number of 8- isomeric prostaglandins on the membrane of the cells after oxidative damage, the destruction of the integrity of the cell membrane, and the change of the fluidity, resulting in the structure of the cells, the impairment of the function, and even the death of the cells. Studies have confirmed that 8-ISO-PGF2a is closely related to cardiovascular system diseases such as coronary atherosclerosis, hypertension, cardiac hypertrophy, Kawasaki disease, and other cardiovascular diseases, such as.KD vascular endothelial dysfunction and elevated oxidative stress levels. The mechanism is that inflammation and injury can produce ROS, and ROS is involved in signal transduction to regulate cells in low water level. Growth, cell adaptive response and other cell functions, when ROS is too much, it can cause cell damage and necrosis through DNA damage and cell signaling, lipid peroxidation, protein denaturation and so on, promoting the infiltration of mononuclear macrophages and lymphocytes from the intima and outer membrane of blood vessels, leading to the whole layer of blood vessels and causing endothelium. Destruction of cells and smooth muscle cells leads to coronary artery dilatation.
In this experiment, 35 hospitalized children with Kawasaki disease in Bethune's First Hospital of Jilin University from March 2010 to October 2011 were selected as group KD, including 21 males and 14 females, ranging from 4 months to 5 years old, with the average age of (2.35 + 1.52) years and the median of 2 years. In the same period, 25 children with febrile diseases after the exclusion of KD in the residential hospital were fever pairs. In the group, there were 15 boys and 10 girls, with an average age of (2.27 + 1.65) years old. 25 healthy children in the outpatient department of Pediatrics, which excluded inflammatory diseases in the outpatient department of Pediatrics, were in the normal control group, 14 men and 11 women. The average age was (1.98 + 1.45) years old, and the test was not unusual. After enzyme linked immunosorbent assay, the serum 8-ISO-PGF was detected in three groups of children. 2A level, the results were analyzed by statistical methods, and the relationship between oxidative stress and the pathogenesis of KD was explored, and the correlation between 8- isomeric prostaglandin and the effect of coronary artery damage and gamma globulin treatment was observed.
The results showed that the level of serum 8-ISO-PGF2a in the KD acute phase and the KD recovery period was significantly higher than that of the fever control group, and the serum 8-ISO-PGF2a level in the KD recovery period was significantly higher than that in the fever control group. The difference was statistically significant in the acute phase of.KD, in the KD recovery period and in the control group as compared with the normal control group, the difference was statistically significant. The oxidative stress marked by 8-ISO-PGF2a may be involved in the pathogenesis of acute vasculitis in children with KD, and may continue to participate in coronary injury during the period of considerable recovery. The serum 8-ISO-PGF2a of children with KD combined with CAL in acute phase is significantly higher than that in the NCAL group. The difference is statistically significant. The acute phase of KD coronary extensor and serum 8-ISO-P The content of GF2a is positively correlated, R=0.937, P < 0.05.8- isomer prostaglandin level is associated with the complications of KD coronary artery injury. It may be valuable for evaluating the probability and long-term prognosis of KD coronary artery injury. The serum 8-ISO-PGF2a in the.IVIG non reactive KD group is significantly higher than that in the IVIG sensitive group, but P=0.05, it needs to be further studied. Research.
Therefore, 8- isomeric prostaglandin participates in the pathophysiological process of KD non characteristic vasculitis. Its recovery level is still high, and it is expected to be a risk assessment of KD coronary artery injury and its prognosis. The research needs to be further studied.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.4

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