本文選題：骨形態(tài)發(fā)生蛋白6　切入點：鐵調(diào)素　出處：《西南醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:慢性腎臟病(Chronic kidney disease,CKD)是一個全球性公共健康問題,如果不進行積極治療可以快速進展為終末期腎臟病(End-Stage Renal Disease,ESRD)而進入維持性腎臟替代治療。貧血與骨礦物質代謝紊亂是CKD患者最常見的兩大并發(fā)癥,而缺鐵是CKD患者貧血的重要原因。近幾年研究顯示鐵調(diào)素(Hepcidin,Hepc)是調(diào)節(jié)鐵穩(wěn)態(tài)最重要的激素,其關鍵調(diào)節(jié)通路是BMP6-HJV-SMAD信號通路,骨形態(tài)發(fā)生蛋白6(Bone Morphogenetic Protein6,BMP6)在其中發(fā)揮著必不可少的作用。新近證據(jù)顯示Hepc除了參與鐵代謝外,與礦物質代謝指標間也存在相關性,提示鐵代謝與礦物質代謝之間相互作用可能與Hepc有關。本研究通過分析Hepc、BMP6與維持性血液透析(Maintenance hemodialysis,MHD)患者貧血、鐵代謝指標的相關性,探討Hepc、BMP6在MHD患者貧血、鐵代謝過程中的重要作用;同時分析Hepc與礦物質代謝指標間的相關性,進一步探討Hepc在MHD患者礦物質代謝中的重要意義。方法:(1)選取內(nèi)江市第二人民醫(yī)院腎內(nèi)科MHD患者67例(MHD組),健康體檢者30例(健康對照組);(2)每位入選者抽取空腹靜脈血液,按照購買的試劑盒說明書規(guī)范操作測定血清BMP6、Hepc、總鐵結合力(total iron binding capacity,TIBC)及1,25二羥基維生素D(1,25(OH)2D)水平,同時于檢驗科檢測貧血指標:紅細胞計數(shù)(RBC)、血紅蛋白(Hb)、紅細胞壓積(Hct);(3)MHD組還需檢測鐵代謝指標:血清鐵(Serum iron,SI)、鐵蛋白(Serum ferritin,SF),并根據(jù)SI與TIBC計算出轉鐵蛋白飽和度(transferrin saturation,TSAT):TSAT=SI/TIBC×100%;礦物質代謝指標:血鈣(Ca)、血磷(P)、甲狀旁腺激素(parathormone,PTH);同時檢測炎癥指標:超敏C反應蛋白(high sensitivity C-reactve protein,hs CRP);肝腎功等臨床指標。(4)收集所有患者臨床資料及實驗數(shù)據(jù)并進行統(tǒng)計分析,正態(tài)分布計量資料采用均數(shù)±標準差表示,非正態(tài)分布計量資料采用中位數(shù)和四分位數(shù)間距表示,計數(shù)資料采用率表示;MHD組與健康對照組間不同指標的比較:正態(tài)分布計量資料采用t檢驗,非正態(tài)分布計量資料采用秩和檢驗,計數(shù)資料采用四格表χ2檢驗;MHD組各指標間相關性分析:正態(tài)分布計量資料采用Pearson直線相關分析,非正態(tài)分布計量資料采用Spearman相關分析;影響因素分析采用多重線性回歸分析。檢驗水準α=0.05,P0.05表示有統(tǒng)計學差異。結果:1、分析MHD組貧血情況及其相關性因素:(1)MHD組Hb水平較健康對照組低(分別為92.36±18.49g/L、142.17±11.95g/L,P0.05),貧血發(fā)生率為97%(65例),Hb達標率為32.8%(22例),Hb不達標率為67.2%(45例);(2)Hb與鐵代謝指標相關性分析示:Hb與Hepc呈負相關(r值為-0.484,P0.05),與SI、TSAT、SF呈正相關(r分別為0.875、0.556、0.527,P0.05),與TIBC無明顯相關關系(r值為-0.052,P=0.676);(3)Hb與礦物質代謝指標相關性分析示:Hb與P、PTH呈負相關(r分別為-0.500、-0.528,P0.05),與Ca呈正相關(r值為0.580,P0.001),與1,25(OH)2D無明顯相關關系(r值為0.042,P=0.736);(4)Hb與炎癥指標相關性分析示:Hb與hs CRP呈負相關(r值為-0.572,P0.05);(5)經(jīng)多重線性回歸分析顯示,SI、Ca是Hb的獨立影響因素。2、分析MHD組Hepc水平及其相關性因素:(1)MHD組Hepc水平較健康對照組明顯升高(分別為49.74±17.42ng/ml、41.89±18.37ng/ml,P0.05);(2)Hepc與貧血指標相關性分析:Hepc與Hb、RBC、Hct呈負相關(r值分別為-0.484、-0.502、-0.475,P0.05);(3)Hepc與鐵代謝指標相關性分析:Hepc與SI呈負相關(r值為-0.398,P0.05),與TSAT、SF呈正相關(r值分別為0.573、0.483,P0.05),與TIBC無相關關系(r值為0.039,P=0.754);(4)Hepc與炎癥指標相關性分析:Hepc與hs CRP呈正相關(r值為0.402,P0.05);(5)經(jīng)多重線性回歸分析顯示,SI、hs CRP是Hepc的獨立影響因素。3、MHD組BMP6水平較健康對照組明顯升高(中位數(shù)分別為42.48pg/ml、26.16pg/m,P0.05),經(jīng)相關性分析顯示BMP6與貧血、鐵代謝指標之間均無明顯相關性。4、分析MHD組Hepc與礦物質代謝指標的相關性:Hepc與PTH呈正相關(r值為0.368,P0.05),與P、Ca、1,25(OH)2D無相關關系(r值分別為-0.049、0.026、0.012,P值分別0.691、0.079、0.147)。結論:1、MHD患者貧血發(fā)生率高,Hb與鐵代謝、礦物質代謝以及炎癥指標密切相關。2、MHD患者血清Hepc水平明顯升高,與貧血、鐵代謝指標具有相關性,表明Hepc升高與MHD患者鐵代謝紊亂相關,在貧血進展中發(fā)揮重要作用。3、MHD患者血清BMP6水平升高,與Hepc、貧血及鐵代謝指標間均無明顯相關性。4、MHD患者血清Hepc與礦物質代謝指標的相關性分析提示血清Hepc水平與PTH相關,與血P、血Ca、1,25(OH)2D無明顯相關性。
[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，

本文編號：1575008