探讨血清Hepcidin与BMP6在维持性血液透析患者中的表达水平及其临床意义

发布时间：2018-03-06 13:24

  本文选题：骨形态发生蛋白6　切入点：铁调素　出处：《西南医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:慢性肾脏病(Chronic kidney disease,CKD)是一个全球性公共健康问题,如果不进行积极治疗可以快速进展为终末期肾脏病(End-Stage Renal Disease,ESRD)而进入维持性肾脏替代治疗。贫血与骨矿物质代谢紊乱是CKD患者最常见的两大并发症,而缺铁是CKD患者贫血的重要原因。近几年研究显示铁调素(Hepcidin,Hepc)是调节铁稳态最重要的激素,其关键调节通路是BMP6-HJV-SMAD信号通路,骨形态发生蛋白6(Bone Morphogenetic Protein6,BMP6)在其中发挥着必不可少的作用。新近证据显示Hepc除了参与铁代谢外,与矿物质代谢指标间也存在相关性,提示铁代谢与矿物质代谢之间相互作用可能与Hepc有关。本研究通过分析Hepc、BMP6与维持性血液透析(Maintenance hemodialysis,MHD)患者贫血、铁代谢指标的相关性,探讨Hepc、BMP6在MHD患者贫血、铁代谢过程中的重要作用;同时分析Hepc与矿物质代谢指标间的相关性,进一步探讨Hepc在MHD患者矿物质代谢中的重要意义。方法:(1)选取内江市第二人民医院肾内科MHD患者67例(MHD组),健康体检者30例(健康对照组);(2)每位入选者抽取空腹静脉血液,按照购买的试剂盒说明书规范操作测定血清BMP6、Hepc、总铁结合力(total iron binding capacity,TIBC)及1,25二羟基维生素D(1,25(OH)2D)水平,同时于检验科检测贫血指标:红细胞计数(RBC)、血红蛋白(Hb)、红细胞压积(Hct);(3)MHD组还需检测铁代谢指标:血清铁(Serum iron,SI)、铁蛋白(Serum ferritin,SF),并根据SI与TIBC计算出转铁蛋白饱和度(transferrin saturation,TSAT):TSAT=SI/TIBC×100%;矿物质代谢指标:血钙(Ca)、血磷(P)、甲状旁腺激素(parathormone,PTH);同时检测炎症指标:超敏C反应蛋白(high sensitivity C-reactve protein,hs CRP);肝肾功等临床指标。(4)收集所有患者临床资料及实验数据并进行统计分析,正态分布计量资料采用均数±标准差表示,非正态分布计量资料采用中位数和四分位数间距表示,计数资料采用率表示;MHD组与健康对照组间不同指标的比较:正态分布计量资料采用t检验,非正态分布计量资料采用秩和检验,计数资料采用四格表χ2检验;MHD组各指标间相关性分析:正态分布计量资料采用Pearson直线相关分析,非正态分布计量资料采用Spearman相关分析;影响因素分析采用多重线性回归分析。检验水准α=0.05,P0.05表示有统计学差异。结果:1、分析MHD组贫血情况及其相关性因素:(1)MHD组Hb水平较健康对照组低(分别为92.36±18.49g/L、142.17±11.95g/L,P0.05),贫血发生率为97%(65例),Hb达标率为32.8%(22例),Hb不达标率为67.2%(45例);(2)Hb与铁代谢指标相关性分析示:Hb与Hepc呈负相关(r值为-0.484,P0.05),与SI、TSAT、SF呈正相关(r分别为0.875、0.556、0.527,P0.05),与TIBC无明显相关关系(r值为-0.052,P=0.676);(3)Hb与矿物质代谢指标相关性分析示:Hb与P、PTH呈负相关(r分别为-0.500、-0.528,P0.05),与Ca呈正相关(r值为0.580,P0.001),与1,25(OH)2D无明显相关关系(r值为0.042,P=0.736);(4)Hb与炎症指标相关性分析示:Hb与hs CRP呈负相关(r值为-0.572,P0.05);(5)经多重线性回归分析显示,SI、Ca是Hb的独立影响因素。2、分析MHD组Hepc水平及其相关性因素:(1)MHD组Hepc水平较健康对照组明显升高(分别为49.74±17.42ng/ml、41.89±18.37ng/ml,P0.05);(2)Hepc与贫血指标相关性分析:Hepc与Hb、RBC、Hct呈负相关(r值分别为-0.484、-0.502、-0.475,P0.05);(3)Hepc与铁代谢指标相关性分析:Hepc与SI呈负相关(r值为-0.398,P0.05),与TSAT、SF呈正相关(r值分别为0.573、0.483,P0.05),与TIBC无相关关系(r值为0.039,P=0.754);(4)Hepc与炎症指标相关性分析:Hepc与hs CRP呈正相关(r值为0.402,P0.05);(5)经多重线性回归分析显示,SI、hs CRP是Hepc的独立影响因素。3、MHD组BMP6水平较健康对照组明显升高(中位数分别为42.48pg/ml、26.16pg/m,P0.05),经相关性分析显示BMP6与贫血、铁代谢指标之间均无明显相关性。4、分析MHD组Hepc与矿物质代谢指标的相关性:Hepc与PTH呈正相关(r值为0.368,P0.05),与P、Ca、1,25(OH)2D无相关关系(r值分别为-0.049、0.026、0.012,P值分别0.691、0.079、0.147)。结论:1、MHD患者贫血发生率高,Hb与铁代谢、矿物质代谢以及炎症指标密切相关。2、MHD患者血清Hepc水平明显升高,与贫血、铁代谢指标具有相关性,表明Hepc升高与MHD患者铁代谢紊乱相关,在贫血进展中发挥重要作用。3、MHD患者血清BMP6水平升高,与Hepc、贫血及铁代谢指标间均无明显相关性。4、MHD患者血清Hepc与矿物质代谢指标的相关性分析提示血清Hepc水平与PTH相关,与血P、血Ca、1,25(OH)2D无明显相关性。
[Abstract]:Objective: chronic kidney disease (Chronic kidney, disease, CKD) is a global public health problem, if not active treatment can rapidly progress to end-stage renal disease (End-Stage Renal Disease, ESRD) to maintain renal replacement therapy. Disorder anemia and bone mineral metabolism is the two most common complications in patients with CKD however, iron deficiency is an important cause of anemia in CKD patients. In recent years, research shows that hepcidin (Hepcidin, Hepc) is the most important hormone that regulates iron homeostasis, the key pathway is BMP6-HJV-SMAD signaling pathway, bone morphogenetic protein 6 (Bone Morphogenetic, Protein6, BMP6) plays an indispensable role in the recent. In addition to evidence that Hepc involved in iron metabolism, there is correlation with the index of mineral metabolism, suggesting that between iron metabolism and mineral metabolism might interact with Hepc through the analysis. Hepc, BMP6 and hemodialysis (Maintenance hemodialysis, MHD) in patients with anemia, correlation, iron metabolism indexes of Hepc, BMP6 in MHD patients with anemia, an important role in the process of iron metabolism; correlation analysis of Hepc and mineral metabolism index at the same time, further explore the significance of Hepc in patients with MHD in mineral metabolism. Methods: (1) a total of 67 cases of MHD patients in Neijiang Second People's Hospital (MHD group) and 30 healthy subjects (healthy control group); (2) each were fasting venous blood, Hepc to buy kit standard operation serum BMP6, total iron binding capacity (total iron binding capacity, TIBC and 1,25) two hydroxy vitamin D (1,25 (OH) 2D) at the laboratory level, detection index: anemia red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct); (3) MHD group also required iron metabolism indexes: Serum Iron (Serum iron, SI), ferritin (Serum ferritin, SF), and according to SI and TIBC to calculate the transferrin saturation (transferrin saturation, TSAT): TSAT=SI/TIBC * 100%; the index of mineral metabolism: calcium (Ca), phosphorus (P), parathyroid hormone (parathormone, PTH); simultaneous detection of inflammatory markers: high sensitivity C reactive protein (high sensitivity C-reactve protein, HS CRP); liver and kidney function and other clinical indicators. (4) of all patients were collected clinical data and experimental data and statistical analysis, normal distribution of measurement data expressed by the mean and standard deviation, non normal distribution of measurement data using the median and four percentile interval said the count data use rate; comparison of different indicators of MHD group and the healthy control group: normal distribution measurement data using t test, non normal distribution of measurement data using rank sum test, the 2 test with count data table four X MHD group each index; 鐩稿叧鎬у垎鏋，

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