本文選題：慢性心力衰竭　切入點(diǎn)：嗜鉻粒蛋白A　出處：《鄭州大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景慢性心力衰竭(chronic heart failure,CHF)是心室收縮或舒張功能障礙所導(dǎo)致的心輸出量不足,組織血流灌注減少,不能滿足機(jī)體需要,造成神經(jīng)內(nèi)分泌系統(tǒng)過度激活的一種復(fù)雜的臨床綜合征,是小兒多種心臟疾病的晚期階段,死亡率高,心室重塑是CHF發(fā)展過程中的重要環(huán)節(jié)。既往CHF的診斷主要依靠臨床癥狀和體征,缺乏早期特異性的診斷指標(biāo),近年來,心力衰竭標(biāo)志物的研究成為熱點(diǎn),其也被越來越多地應(yīng)用于CHF的早期診斷和病情評(píng)估。嗜鉻粒蛋白A(chromograninA,CgA)是一種可溶性多肽類物質(zhì),具有抑制血管收縮,拮抗腎上腺素、內(nèi)皮素等的作用,并參與心室重塑過程。尾加壓素Ⅱ(human urotensinⅡ,UⅡ)是迄今為止發(fā)現(xiàn)的最強(qiáng)大的收縮血管的物質(zhì),可增強(qiáng)兒茶酚胺、內(nèi)皮素、血管緊張素Ⅱ的作用。近年來CgA和UⅡ在心血管系統(tǒng)中的表達(dá)也逐漸受到關(guān)注。目的本研究旨在通過測(cè)定不同心功能分級(jí)和病因的CHF患者治療前后血清的CgA和UⅡ的水平變化,探討CgA和UⅡ之間的相關(guān)性,以及治療前CgA和UⅡ與心功能分級(jí)及心室重塑指標(biāo)的關(guān)系及其意義,探討其在小兒慢性心力衰竭中的應(yīng)用價(jià)值及其臨床意義。方法選取2015年6月至2016年6月于鄭州大學(xué)第一附屬醫(yī)院小兒內(nèi)科確診為CHF的32例患兒為心衰組,其中心內(nèi)膜彈力纖維增生癥9例,擴(kuò)張型心肌病23例;另選取門診健康體檢兒童20例為正常對(duì)照組。采用酶聯(lián)免疫吸附法(ELISA法)測(cè)定心衰組治療前后血清CgA及UⅡ水平;采用雙向側(cè)流免疫法測(cè)定氨基末端腦鈉肽前體(NT-proBNP)水平;超聲心動(dòng)圖測(cè)定心室重塑指標(biāo)。應(yīng)用SPSS 21.0統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)分析,正態(tài)分布的計(jì)量資料采用均數(shù)±標(biāo)準(zhǔn)差(`X±S)表示;非正態(tài)分布的計(jì)量資料采用中位數(shù)(四分位間距)[M(P25,P75)]表示。正態(tài)分布且方差齊的計(jì)量資料兩組間比較采用t檢驗(yàn),多組間兩兩比較采用LSD-t檢驗(yàn),方差不齊時(shí)采用校正的t檢驗(yàn)。非正態(tài)分布、方差不齊或總體分布不詳?shù)挠?jì)量資料的兩組間比較采用Mann-Whitney U檢驗(yàn),多組之間比較采Kruskal-Wallis檢驗(yàn),多組間兩兩比較采用Bonferroni法。計(jì)數(shù)資料采用例數(shù)表示,兩組間比較采用c2檢驗(yàn)。關(guān)聯(lián)性分析采用Pearson相關(guān)或Spearman相關(guān)分析。當(dāng)P0.05時(shí),認(rèn)為差異具有統(tǒng)計(jì)學(xué)意義。結(jié)果(1)心衰組患兒治療前血清CgA濃度、NT-proBNP濃度明顯高于對(duì)照組(其Z值分別為-6.019、-6.019),且治療后兩者的血清學(xué)濃度較治療前明顯下降(其Z值分別為-4.398,-3.585);治療前血清UⅡ濃度低于對(duì)照組(Z=-5.342),治療后其濃度較治療前升高(Z=-4.134),其差異均具有統(tǒng)計(jì)學(xué)意義(P0.001);(2)心衰組治療前心功能分級(jí)Ⅱ級(jí)組的血清CgA、NT-proBNP水平與對(duì)照組差異不具有統(tǒng)計(jì)學(xué)意義(P0.05)。心功能分級(jí)Ⅲ級(jí)、Ⅳ級(jí)組的血清CgA、NT-proBNP水平高于對(duì)照組(P0.05);并且隨著心功能不全程度的加重而逐漸升高(P0.05)。心功能不全Ⅱ級(jí)、Ⅲ級(jí)、Ⅳ級(jí)組患兒的UⅡ濃度均低于對(duì)照組(P0.05),并且隨著心功能不全程度的加重而逐漸降低,異有統(tǒng)計(jì)學(xué)意義(P0.05);(3)EFE組和DCM組的血清CgA、UⅡ濃度差異無統(tǒng)計(jì)學(xué)意義(P0.05);(4)心衰組治療前患兒血清CgA濃度分別與LVMI、NT-proBNP、心功能分級(jí)成正相關(guān)(r分別為0.394、0.585及0.720,P0.05),與LVEF、LVFS、UⅡ成負(fù)相關(guān)(r分別為-0.599、-0.573及-0.628,P0.05)。血清UⅡ分別與LVEF、LVFS成正相關(guān)(r分別為0.444、0.472,P0.05),而與NT-proBNP、心功能分級(jí)成負(fù)相關(guān)(r分別為-0.654、-0.866,P0.05),而與LVMI無明顯相關(guān)性(P0.05)。結(jié)論(1)CgA可能參與CHF患兒心室重塑;(2)測(cè)定血清CgA和UⅡ可為CHF的診斷、心功能分級(jí)以及評(píng)估心衰治療效果提供客觀依據(jù)。
[Abstract]:Background: chronic heart failure (chronic heart failure, CHF) is ventricular systolic or diastolic dysfunction of cardiac output caused by insufficient tissue perfusion reduced, can not meet the needs of the body, causing a complex clinical excessive activation of the neuroendocrine system syndrome, is a late stage, a variety of pediatric heart disease mortality, ventricular remodeling an important link in the development of CHF. The diagnosis of CHF mainly depends on the clinical symptoms and signs, the lack of early diagnosis index, specific markers of heart failure in recent years, research has become a hot spot, it is early diagnosis and assessment of disease is more and more used in the CHF. Chromogranin A (chromograninA, CgA) is a soluble polypeptide, inhibit vasoconstriction, antagonistic effects of endothelin and adrenaline, and participate in the ventricular remodeling process. Urotensin II (human urotensin II, U II) is by far the most powerful vasoconstrictor substances can enhance catecholamines, endothelin, angiotensin II. In recent years, the expression of CgA and U II in cardiovascular system has attracted more and more attention. The purpose of this study aims to the change of serum CgA and U level II after grading the etiology and treatment of patients with CHF in different heart function, explore the relationship between CgA and U II, and former CgA and U II and the classification of cardiac function and ventricular remodeling index in treatment of the relationship and significance, to explore its application value in the value in children with chronic heart failure and its clinical significance. Methods from June 2015 to June 2016 in the first the Affiliated Hospital of Zhengzhou University Department of Pediatrics 32 children diagnosed as CHF for heart failure group, 9 cases of the center of endocardial fibroelastosis, dilated cardiomyopathy in 23 cases; the other 20 healthy children were selected as normal The control group. Using enzyme-linked immunosorbent assay (ELISA) determination of serum CgA and U levels before and after treatment of heart failure group; two side determination of N-terminal pro brain natriuretic peptide (NT-proBNP) level flow immunoassay; echocardiography ventricular remodeling index. SPSS 21 software was used for data analysis, measurement data the normal distribution by the mean and standard deviation (`X + S); non normal distribution of measurement data using the median (four percentile interval) [M (P25, P75)]. The measurement data is normal distribution and variance of the two groups were compared using t test and multiple comparison between the 22 groups by LSD-t test of homogeneity of variance using t calibration. Non normal distribution, homogeneity of variance or the overall distribution of unknown measurement data of the two groups were compared using Mann-Whitney U test and comparison among multiple groups using Kruskal-Wallis test, multiple comparison between the 22 groups by counting Bonferroni method. Data is expressed by the number of cases, the two groups were compared using C2 test. Correlation analysis using Pearson correlation or Spearman correlation analysis. When P0.05, considered statistically significant. Results (1) heart failure group before treatment, serum CgA concentration, NT-proBNP concentration was significantly higher than the control group (Z = -6.019, -6.019) after the treatment, and the serum concentration of the two was significantly lower than that before treatment (Z = -4.398, -3.585); serum U II concentration lower than the control group (Z=-5.342), after treatment the concentration higher than before treatment (Z=-4.134), the differences were statistically significant (P0.001); (2) serum CgA heart failure group, heart function before treatment of grade II group, and control group NT-proBNP difference was not statistically significant (P0.05). Class III grade of heart function, serum CgA IV group, NT-proBNP was higher than the control group (P0.05); and with the degree of heart failure 鍔犻噸鑰岄，

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