本文選題：川崎病 + 8-異構(gòu)前列腺素��； 參考：《吉林大學(xué)》2012年碩士論文

【摘要】：KD是一種以全身血管炎變?yōu)橹饕±硖攸c(diǎn)的急性發(fā)熱性出疹性小兒疾病，可病發(fā)冠狀動(dòng)脈損害，成為后天獲得性心臟病最常見的原因。近幾十年來(lái)，KD的發(fā)病率呈逐年升高趨勢(shì)，雖然KD冠狀動(dòng)脈改變比例有所下降，但丙種球蛋白治療無(wú)反應(yīng)型KD比例升高，KD的病因及發(fā)病機(jī)制研究一直是醫(yī)學(xué)家研究的熱點(diǎn)和難點(diǎn)�，F(xiàn)在的觀點(diǎn)趨向于：外界環(huán)境及各種致病因子作用于具有遺傳易感性的個(gè)體，導(dǎo)致機(jī)體免疫失衡，釋放細(xì)胞因子、化學(xué)分子、活性氧等一系列炎癥因子，引起全身非特異性的血管炎，尤其以冠狀動(dòng)脈為著。8-ISO-PGF2a具有化學(xué)穩(wěn)定性，是過(guò)氧化反應(yīng)特異的產(chǎn)物，能在體內(nèi)形成，由于該物質(zhì)的生成不需酶的參與（與環(huán)氧化酶無(wú)關(guān)），在體液中能夠穩(wěn)定存在，被認(rèn)為是判斷活體內(nèi)自由基氧化強(qiáng)度和臨床上評(píng)價(jià)抗氧化劑療效的最理想的生化指標(biāo)。近年又有研究發(fā)現(xiàn)血管炎、心血管系統(tǒng)疾病的發(fā)病與氧化損傷和抗氧化防護(hù)的失衡有關(guān)[69]。8-ISO-PGF2a具有明顯的收縮血管作用[70]，且與去甲腎上腺素和血管緊張素協(xié)同促進(jìn)血管收縮；刺激血管內(nèi)皮細(xì)胞分化、增值；促使血小板的聚集和變形；引起成纖維細(xì)胞和心肌細(xì)胞的增殖；氧化損傷后細(xì)胞膜上酯化的8-異構(gòu)前列腺素?cái)?shù)量增多，細(xì)胞膜的完整性被破壞，流動(dòng)性發(fā)生改變，從而導(dǎo)致細(xì)胞的結(jié)構(gòu)、功能受損，甚至導(dǎo)致細(xì)胞死亡。研究證實(shí)8-ISO-PGF2a與冠狀動(dòng)脈粥樣硬化、高血壓、心肌肥厚、川崎病等心血管系統(tǒng)疾病密切相關(guān)。KD血管內(nèi)皮功能障礙與氧化應(yīng)激水平升高有關(guān)。其機(jī)制是機(jī)體的炎癥以及損傷可以產(chǎn)生活性氧（ROS），ROS在低水平時(shí)，參與信號(hào)傳導(dǎo)來(lái)調(diào)節(jié)細(xì)胞生長(zhǎng)、細(xì)胞適應(yīng)性反應(yīng)等細(xì)胞功能，，當(dāng)ROS過(guò)多時(shí)，它可以通過(guò)DNA損傷以及細(xì)胞信號(hào)傳導(dǎo)、脂質(zhì)過(guò)氧化反應(yīng)、蛋白質(zhì)變性等途徑引起細(xì)胞損傷甚至壞死，促進(jìn)單核巨噬細(xì)胞及淋巴細(xì)胞從血管內(nèi)膜及外膜滲透遷移，導(dǎo)致血管全層炎癥，導(dǎo)致內(nèi)皮細(xì)胞及平滑肌細(xì)胞破壞，導(dǎo)致冠脈擴(kuò)張。 本實(shí)驗(yàn)選取2010年3月至2011年10月吉林大學(xué)白求恩第一醫(yī)院小兒心血管科確診川崎病的住院患兒35例為KD組，其中男21例，女14例，年齡4個(gè)月至5歲不等，平均年齡（2.35±1.52）歲，中位數(shù)為2歲。同期住院的排除KD后的發(fā)熱性疾病患兒25例為發(fā)熱對(duì)照組，其中男孩15例，女孩10例，平均年齡（2.27±1.65）歲。同期在我院兒科門診進(jìn)行體檢排除炎癥性疾病的健康兒童25例為正常對(duì)照組，男14例，女11例，平均年齡（1.98±1.45）歲，化驗(yàn)檢查未見異常。經(jīng)過(guò)酶聯(lián)免疫吸附試驗(yàn)，檢測(cè)三組患兒血清8-ISO-PGF2a素水平，通過(guò)統(tǒng)計(jì)學(xué)方法對(duì)結(jié)果進(jìn)行分析，探討氧化應(yīng)激與KD的發(fā)病機(jī)制的關(guān)系，觀察8-異構(gòu)前列腺素與冠狀動(dòng)脈損害及丙種球蛋白治療效果的相關(guān)性。 研究結(jié)果發(fā)現(xiàn)KD急性期與KD恢復(fù)期、發(fā)熱對(duì)照組比較血清8-ISO-PGF2a水平升高明顯，且KD恢復(fù)期患兒血清8-ISO-PGF2a水平較發(fā)熱對(duì)照組升高明顯，差異有統(tǒng)計(jì)學(xué)意義。KD急性期、KD恢復(fù)期、發(fā)熱對(duì)照組較正常對(duì)照組升高明顯，差異有統(tǒng)計(jì)學(xué)意義。表明8-ISO-PGF2a為標(biāo)志的氧化應(yīng)激可能參與KD患兒急性期血管炎的發(fā)病機(jī)制，且在相當(dāng)時(shí)間的恢復(fù)期中，有可能繼續(xù)參與冠脈的損傷。急性期KD合并CAL組患兒血清8-ISO-PGF2a較NCAL組明顯升高，差異有統(tǒng)計(jì)學(xué)意義。急性期KD冠脈擴(kuò)張量和血清8-ISO-PGF2a含量呈正相關(guān)，R=0.937，P＜0.05。8-異構(gòu)前列腺素水平與KD冠狀動(dòng)脈損傷的并發(fā)癥有相關(guān)性，可能對(duì)于評(píng)估KD冠狀動(dòng)脈損傷發(fā)生的概率及遠(yuǎn)期預(yù)后有一定價(jià)值。IVIG無(wú)反應(yīng)型KD組患兒血清8-ISO-PGF2a較IVIG敏感組相比升高顯著，但P=0.05，需進(jìn)一步研究。 因此，8-異構(gòu)前列腺素參與KD非特性血管炎的病理生理過(guò)程。其恢復(fù)期水平仍較高，有望成為評(píng)估KD冠狀動(dòng)脈損傷的危險(xiǎn)度及其預(yù)后。為抗氧化劑在冠狀動(dòng)脈病變中的應(yīng)用提供了廣闊的前景。但將異構(gòu)前列腺素作為治療冠狀動(dòng)脈病變靶點(diǎn)的研究有待進(jìn)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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R725.4

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 陳琳;匡希斌;;異構(gòu)前列腺素與臨床氧化應(yīng)激性損傷疾病[J];中國(guó)動(dòng)脈硬化雜志;2005年05期

本文編號(hào)：2029158