本文選題：Klotho　切入點(diǎn)：成纖維細(xì)胞生長因子-23　出處：《大連醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：通過酶聯(lián)免疫吸附試驗(yàn)（enzyme-linked immunosorbent assay，ELISA）檢測慢性腎臟病（chronic kidney disease，CKD）患者不同腎功能階段血清Klotho和成纖維細(xì)胞生長因子23（fibroblast growth factor23，，F(xiàn)GF-23）水平的變化，探討其與礦物質(zhì)代謝及心臟結(jié)構(gòu)的關(guān)系。 方法：選取2013年7月至2014年1月在大連醫(yī)科大學(xué)附屬第二醫(yī)院腎內(nèi)科住院的CKD患者，共75例。排除標(biāo)準(zhǔn)：嚴(yán)重的感染、肝膽疾病、活動(dòng)性消耗性疾�。ㄈ鐞盒阅[瘤或肺結(jié)核）；急性心肌梗死、心力衰竭、急性腦血管疾��；原發(fā)性甲狀旁腺疾病、甲狀旁腺切除、腎移植術(shù)后患者。另選取同期在本院體檢的健康查體者作為對照組，共13例。根據(jù)腎小球?yàn)V過率（estimated glomerular filtrationrate，eGRF）將CKD患者分為：CKD2期12例、CKD3期14例、CKD4期12例、CKD5期37例（其中包括非透析組21例、血透組10例和腹透組6例）。又根據(jù)左心室肥厚（left ventricular hypertrophy，LVH）診斷標(biāo)準(zhǔn)（左心室心肌質(zhì)量指數(shù)[leftventricular mass index，LVMI]，男性≥135g/m2、女性≥110g/m2）將CKD2-5期非透析患者分為LVH組14例和非LVH組45例。收集所有研究對象的一般臨床資料，包括性別、年齡、體重指數(shù)、原發(fā)疾病等；應(yīng)用自動(dòng)分析儀檢測血紅蛋白、血清白蛋白、甘油三酯、膽固醇、低密度脂蛋白膽固醇、高密度脂蛋白膽固醇、血清肌酐、血鈣、血磷；應(yīng)用免疫化學(xué)熒光法檢測全段甲狀旁腺激素（intact parathyroidhormone，iPTH）；根據(jù)MDRD公式計(jì)算eGRF，并計(jì)算校正鈣、鈣磷乘積。應(yīng)用ELISA法檢測血清Klotho和FGF-23濃度。彩色多普勒超聲測定左心室后壁厚度、室間隔厚度、左心室舒張末期內(nèi)徑，計(jì)算LVMI。采用SPSS13.0統(tǒng)計(jì)學(xué)軟件進(jìn)行統(tǒng)計(jì)分析和處理，P0.05為差異具有統(tǒng)計(jì)學(xué)意義。另外，應(yīng)用局部加權(quán)回歸散點(diǎn)平滑法（locally weighted scatter plot smoothing，LOESS）觀察血清Klotho、FGF-23與eGRF的關(guān)系。 結(jié)果： 1. CKD2-5期患者（非透析），血清Klotho水平均低于對照組（P＜0.05）。CKD4期、CKD5期血清Klotho水平均低于CKD2期、CKD3期（P＜0.05）。CKD3-5期血清FGF-23水平均高于對照組（P＜0.05）。CKD4期血清FGF-23水平高于CKD2期、CKD3期（P＜0.05）。CKD5期血清FGF-23水平高于CKD2-4期（P＜0.05）。CKD2-5期血鈣水平相近（P＞0.05）。CKD2期、CKD3期血磷較對照組略低（P＞0.05）。血清iPTH、血磷和鈣磷乘積僅在對照組和CKD5期之間存在顯著性差異。相關(guān)性分析顯示，血清Klotho與血清FGF-23（r=-0.524，P＜0.01）、血磷（r=-0.486，P＜0.01）、鈣磷乘積（r=-0.494，P＜0.01）、iPTH（r=-0.466，P＜0.01）均呈負(fù)相關(guān)。在校正年齡、性別及eGFR后，血清Klotho仍與年齡、eGFR獨(dú)立相關(guān)。血清FGF-23與血磷（r=0.658，P＜0.01）、鈣磷乘積（r=0.638，P＜0.01）、iPTH（r=0.603，P＜0.01）均呈正相關(guān)。 2. CKD5期血透組、腹透組和非透析組的患者中，非透析組血清Klotho水平高于血透組、腹透組（P＜0.05），血清FGF-23水平與血透組、腹透組無顯著性差異，血清iPTH低于血透組（P＜0.01）、高于腹透組（P＞0.05）。血透組血清Klotho水平低于腹透組（P＞0.05），而血清iPTH明顯高于腹透組（P＜0.05）。 3.應(yīng)用LOESS觀察CKD2-5期患者（非透析）血清Klotho、FGF-23、iPTH、血鈣、磷與eGFR的關(guān)系，發(fā)現(xiàn)血清Klotho與eGFR呈線性相關(guān)，eGFR每下降1ml/min，血清Klotho下降4.79pg/ml（95%CI3.73-5.86pg/ml，P＜0.01）。校正年齡后，eGFR每下降1ml/min，血清Klotho下降4.75pg/ml（95%CI3.83-5.66pg/ml，P＜0.01）。血清FGF-23、iPTH、血磷均與eGFR呈非線性相關(guān)。血清FGF-23在CKD2期、iPTH和血磷在CKD2-3期變化不大，后隨eGFR下降而急劇上升。FGF-23在eGFR下降至50ml/min時(shí)迅速升高，而血iPTH在eGFR下降至27ml/min時(shí)、血磷在eGFR下降至26ml/min時(shí)急劇升高。 4. CKD2-5期患者（非透析）中，LVH組體重指數(shù)、血紅蛋白、低密度脂蛋白膽固醇、FGF-23均高于非LVH組（P0.05），而血清Klotho明顯低于非LVH組（P0.01）。LVMI與FGF-23呈正相關(guān)（r=0.313，P＜0.01），LVMI與Klotho呈負(fù)相關(guān)（r=-0.283，P＜0.01）。進(jìn)一步行多因素Logistic回歸分析顯示，血清Klotho（OR=0.995，P＜0.01）和血清FGF-23（OR=1.002，P＜0.05）均為CKD患者LVH發(fā)生的相關(guān)因素。 結(jié)論： 1.慢性腎臟病非透析患者血清FGF-23的升高早于血磷和血甲狀旁腺激素的增高，而血清Klotho的下降先于血清FGF-23的升高，故Klotho可能是慢性腎臟病礦物質(zhì)代謝紊亂的早期生物標(biāo)志物。 2. Klotho、FGF-23可能是慢性腎臟病非透析患者左心室肥厚的影響因素，Klotho是保護(hù)性因素，而FGF-23是獨(dú)立危險(xiǎn)因素。
[Abstract]:Objective: by enzyme-linked immunosorbent assay (enzyme-linked immunosorbent, assay, ELISA) detection of chronic kidney disease (chronic kidney, disease, CKD) in patients with different renal function stage serum Klotho and fibroblast growth factor 23 (fibroblast growth, Factor23, FGF-23) level changes, discuss the relationship between the mineral metabolism and cardiac structure.
Methods: from July 2013 to January 2014 on renal function in patients with CKD hospitalized in Second Affiliated Hospital of Dalian Medical University, a total of 75 cases of hepatobiliary disease. Exclusion criteria: severe infection, active wasting diseases (such as cancer or tuberculosis); acute myocardial infarction, heart failure, acute cerebral vascular disease; primary parathyroid diseases, parathyroidectomy, patients after renal transplantation were selected in our hospital. The other healthy subjects served as control group, 13 cases in total. According to glomerular filtration rate (estimated, glomerular filtrationrate, eGRF) CKD patients were divided into 12 cases of stage CKD2, stage CKD3 14 cases, CKD4 12 cases, stage CKD5 in 37 cases (including 21 cases of non dialysis patients, hemodialysis and peritoneal dialysis group and 10 cases in group 6 cases). According to the left ventricular hypertrophy (left ventricular, hypertrophy, LVH) diagnostic criteria (left ventricular mass index [LEFTVENTRICULAR mass index, LVMI], The male is more than 135g/m2, 110g/m2 or CKD2-5) female non dialysis patients were randomly divided into LVH group of 14 cases and 45 cases in non LVH group. The clinical data were collected from all participants, including gender, age, body mass index, primary disease detection; application of automatic analyzer hemoglobin, serum albumin, triglyceride, cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, serum creatinine, blood calcium, blood phosphorus; detection of parathyroid hormone by immunohistochemistry fluorescence method (intact parathyroidhormone, iPTH); eGRF was calculated according to MDRD formula, and calculate the corrected calcium, calcium and phosphorus product. ELISA method was used to detect the serum Klotho and FGF-23 concentration. The color Doppler ultrasound of left ventricle determination of posterior wall thickness, interventricular septum thickness, left ventricular end diastolic diameter, calculation of LVMI. using SPSS13.0 statistical software for statistical analysis and processing, P0.05 differed significantly In addition, locally weighted scatter plot smoothing (LOESS) was used to observe the relationship between serum Klotho, FGF-23 and eGRF.
Result錛

本文編號：1595372