儿童急性白血病血清Hepcidin的表达及其与铁代谢的关系

发布时间：2018-08-17 14:33

【摘要】：背景和目的铁调素(Hepcidin)认为是一种在肝脏合成并由其分泌的多肽类物质,在机体铁代谢的调节过程中起到重要作用。近年来关于Hepcidin在恶性肿瘤方面的研究发现患者血清Hepcidin水平异常,不仅在肿瘤疾病的铁代谢中起核心作用,亦与肿瘤的发生、发展有密切关系。目前,Hepcidin在肿瘤疾病方面的研究多集中在其与癌性贫血的关系上,关于Hepcidin在儿童急性白血病(Acute leukemia,AL)中的表达情况及其与铁代谢的关系研究较少。本实验采用酶联免疫吸附法(Enzyme-linked immunosorbent assay,ELISA)检测AL患儿血清中Hepcidin、IL-6的表达水平,并送检转铁蛋白(transferrin,TRF),铁蛋白(Ferritin,FN)的血清浓度,分析Hepcidin表达异常的机制,并通过相关性分析,了解儿童AL中Hepcidin异常与AL铁代谢的关系。方法选取2014年11月至2015年11月期间在郑州大学第一附属医院儿科病区确诊AL患儿63例作为研究对象,选取同时期健康儿童30例作为对照组。随访疗效至2016年9月30日,根据疗效评价标准进行评价,分为缓解组和未缓解组。收集AL患儿初治时、治疗后的外周血以及健康儿童外周血。采用酶联免疫吸附法(Enzyme-linked immunosorbent assay,ELISA)分别检测AL患儿初治时、治疗后和30例健康对照组儿童血清中Hepcidin、IL-6的表达量,并检测所有对象血清中TRF、FN的表达量,比较AL初治组、治疗后及对照组Hepcidin、IL-6、TRF、FN血清水平差异,以及缓解组与未缓解组各指标水平差异,同时分析Hepcidin与IL-6及Hepcidin与铁代谢相关指标之间的相关性。结果1纳入对象的一般情况AL组患儿与健康对照组儿童性别构成比,经过χ2检验比较差异无统计学意义(χ2=0.031,P=0.860);年龄经过独立样本t检验比较差异无统计学意义(t=0.332,P=0.756)。2.AL初治组与对照组血清Hepcidin、IL-6及铁代谢指标TRF、FN水平比较AL初治组血清Hepcidin水平、IL-6水平、FN水平高于对照组,差异均具有统计学意义(P0.001);AL初治组血清TRF水平低于对照组,差异亦具有统计学意义(P0.001)。3.AL组治疗前后血清Hepcidin、IL-6及铁代谢指标TRF、FN水平比较AL缓解组治疗前血清Hepcidin水平、IL-6水平、FN水平高于治疗后,差异均具有统计学意义(P0.001);AL缓解组治疗前血清TRF水平低于治疗后,差异亦具有统计学意义(P0.001);AL未缓解组治疗前后血清Hepcidin水平、IL-6水平、FN水平及TRF水平差异无统计学意义(P0.05)。4.AL缓解组与未缓解组血清Hepcidin、IL-6及铁代谢指标TRF、FN水平比较无论在化疗前或者化疗后,AL未缓解组血清Hepcidin水平、IL-6水平、FN水平均高于缓解组,差异均具有统计学意义(P0.001);无论在化疗前或者化疗后,AL未缓解组血清TRF水平均低于缓解组,差异亦均具有统计学意义(P0.001)。5.AL患儿血清Hepcidin与IL-6及血清Hepcidin与铁代谢指标FN、TRF水平的相关性分析在AL初治组中血清Hepcidin的水平与血清IL-6水平呈正相关(r=0.866,P0.001);铁代谢相关指标血清TRF水平与血清Hepcidin水平呈负相关(r=-0.834,P0.001),血清FN水平与血清Hepcidin水平呈正相关(r=0.750,P0.001),差异均具有统计学意义。结论1.AL患儿体内存在Hepcidin的表达异常及铁代谢的紊乱。2.AL患儿Hepcidin、IL-6、FN的血清表达水平高于健康儿童,这些分子水平可作为儿童AL的辅助诊断指标;Hepcidin、IL-6、FN以及TRF的血清表达水平在化疗缓解前后以及缓解与未缓解组间均有差异,提示各指标水平变化可为评判儿童AL治疗效果提供依据。3.AL患儿Hepcidin血清表达水平与IL-6血清表达水平呈正相关,提示IL-6是AL患儿体内Hepcidin水平升高的原因之一;TRF血清表达水平与Hepcidin的血清表达水平呈负相关,FN血清表达水平与Hepcidin血清表达水平呈正相关,提示Hepcidin参与儿童AL铁代谢的紊乱。
[Abstract]:BACKGROUND AND OBJECTIVE Hepcidin is considered to be a polypeptide synthesized and secreted by the liver and plays an important role in the regulation of iron metabolism in the body. Hepcidin expression in childhood acute leukemia (AL) and its relationship with iron metabolism were less. Enzyme-linked immunosorbent assay (ELISA) was used in this study. Mmunosorbent assay (ELISA) was used to detect the expression of hepcidin and IL-6 in serum of children with AL. Serum concentrations of transferrin (TRF), ferritin (FN) were detected. The mechanism of abnormal expression of hepcidin was analyzed. The relationship between abnormal expression of hepcidin and iron metabolism in children with AL was studied by correlation analysis. Sixty-three children with AL diagnosed in the pediatric ward of the First Affiliated Hospital of Zhengzhou University in November 15 were selected as the study subjects and 30 healthy children were selected as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of Hepcidin and IL-6 in the serum of children with AL at the beginning of treatment, after treatment and 30 healthy controls, and to detect the expression of TRF and FN in the serum of all subjects. Results 1 There was no significant difference in sex composition between AL group and healthy control group (_2 = 0.031, P = 0.031). The serum levels of hepcidin, IL-6, and iron metabolism index TRF, FN in the primary treatment group and the control group were significantly lower than those in the primary treatment group (P 0.001). The serum levels of hepcidin, IL-6 and FN in the primary treatment group were significantly higher than those in the control group (P 0.001). The levels of serum hepcidin, IL-6, iron metabolism index TRF and FN in AL remission group were higher than those in AL remission group (P 0.001). The levels of serum TRF in AL remission group were lower than those in AL remission group (P 0.001). There was no significant difference in serum levels of Hepcidin, IL-6, FN and TRF between remission group and non-remission group (P 0.05). Levels of serum hepcidin, IL-6 and serum hepcidin were significantly higher than those of remission group (P 0.001), and the correlation between serum hepcidin, iron metabolism index FN and TRF was statistically significant (P 0.001). Serum levels of hepcidin were positively correlated with serum levels of IL-6 (r = 0.866, P 0.001), serum levels of TRF were negatively correlated with serum levels of hepcidin (r = - 0.834, P 0.001), serum levels of FN were positively correlated with serum levels of hepcidin (r = 0.750, P 0.001), and the differences were statistically significant. Abnormal expression of pcidin and disorder of iron metabolism. 2. The serum levels of hepcidin, IL-6 and FN in children with AL were higher than those in healthy children, and these molecular levels could be used as auxiliary diagnostic indicators for children with AL. The serum levels of Hepcidin, IL-6, FN and TR F were different before and after chemotherapy remission and between remission and non-remission groups, suggesting that the levels of each indicator were different. The expression of hepcidin in serum was positively correlated with that of IL-6, suggesting that IL-6 was one of the reasons for the elevated level of hepcidin in children with AL, the expression of TRF in serum was negatively correlated with that of Hepcidin, and the expression of FN in serum was negatively correlated with that of Hepcidin. The level is positively correlated, suggesting that Hepcidin is involved in the disorder of AL iron metabolism in children.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.71

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