慢性腎臟病患者血清妊娠相關(guān)血漿蛋白-A水平與頸動(dòng)脈內(nèi)中膜厚度的關(guān)系
發(fā)布時(shí)間：2018-08-26 11:03
【摘要】：目的:檢測(cè)慢性腎臟病(Chronic kidney disease,CKD)患者血清妊娠相關(guān)血漿蛋白-A(Pregnancy-Associated Plasma Protein-A,PAPP-A)、超敏C反應(yīng)蛋白(high sensitive-C-reactive protein,Hs-CRP)水平的變化和頸動(dòng)脈超聲,分析CKD患者PAPP-A與頸動(dòng)脈內(nèi)中膜厚度(intima-media thickness,IMT)的相關(guān)性及其影響因素。方法:1實(shí)驗(yàn)組:選取2014年1月至2014年8月在河北醫(yī)科大學(xué)第二醫(yī)院腎內(nèi)科住院的非透析CKD患者71例,男性44例,女性27例,年齡20~68歲,平均年齡44.95±12.86歲,原發(fā)病分別為慢性腎小球腎炎69例,成人常染色體顯性遺傳性多囊腎2例。根據(jù)CKD-EPI公式,計(jì)算腎小球?yàn)V過率(e GRF[ml/min/1.73m2])進(jìn)行分組,將CKD患者分為CKD3期、CKD4期和CKD5期組。其中,CKD3期組24例,男14例,女10例,年齡42.17±13.55歲,CKD4期組17例,男14例,女3例,年齡47.44±11.31歲,CKD5期組30例,男16例,女14例,年齡46.79±13.24歲。排除標(biāo)準(zhǔn):(1)3個(gè)月內(nèi)發(fā)生急性感染或創(chuàng)傷,(2)慢性腎功能不全急性加重,(3)結(jié)締組織病,(4)糖尿病腎病,(5)家族性高脂血癥,(6)入選前3個(gè)月使用過激素或免疫抑制劑治療,(7)妊娠或分娩,(8)入選前3個(gè)月內(nèi)發(fā)生急性心腦血管事件,(9)高尿酸血癥,另選取同期我院體檢中心的健康體檢者16例為對(duì)照組,其中男性7人,女性9人,年齡47.31±10.42歲。2采用酶聯(lián)免疫吸附試驗(yàn)(ELISA)方法檢測(cè)PAPP-A的濃度,免疫比濁法測(cè)定Hs-CRP的濃度,采用飛利浦IE33彩色多普勒超聲檢測(cè)儀檢測(cè)患者頸動(dòng)脈內(nèi)膜中層厚度IMT及斑塊。連續(xù)測(cè)量2個(gè)心動(dòng)周期,取其平均值作為頸動(dòng)脈IMT值,IMT1.0mm為正常,IMT≥1.0 mm視為早期動(dòng)脈粥樣硬化,IMT≥1.2mm或局部呈混合回聲或強(qiáng)回聲則為有斑塊形成。同時(shí)測(cè)定血常規(guī)、肝功能、腎功能、血脂和甲狀旁腺激素(IPTH)等生化指標(biāo),并記錄患者一般資料:性別、年齡、原發(fā)病、既往有無心血管疾病史、血壓、體質(zhì)量指數(shù)(BMI)、吸煙史等。3采用SPSS13.0軟件對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析,取α=0.05為檢驗(yàn)水準(zhǔn),以P0.05為差異,代表有統(tǒng)計(jì)學(xué)意義。結(jié)果:1 CKD患者血清PAPP-A和Hs-CRP水平:CKD患者血清PAPP-A水平[63.24(62.14)ng/ml]較對(duì)照組[24.26(22.25)ng/ml]明顯升高(P0.01)。CKD3、4、5期患者血清PAPP-A水平分別為38.13(38.85)ng/ml、61.69(61.20)ng/ml、84.20(88.00)ng/ml,均較對(duì)照組顯著升高,差異有統(tǒng)計(jì)學(xué)意義(P均0.01)。且隨著腎功能的惡化血PAPP-A呈進(jìn)行性升高。CKD患者血清Hs-CRP水平為[11.14(12.03)mg/L]較對(duì)照組[3.15(3.02)mg/L]顯著升高(P0.01),CKD3、4、5期患者血清Hs-CRP水平分別為7.17(7.15)mg/L、11.04(10.98)mg/L、14.37(15.12)mg/L。組間比較結(jié)果顯示,CKD4期組明顯高于CKD3期組,差異有統(tǒng)計(jì)學(xué)意義(P均0.01),CKD5期組分別高于CKD3期組和CKD4期組(P0.01)。2 CKD患者頸動(dòng)脈超聲檢測(cè)結(jié)果:CKD患者頸動(dòng)脈硬化(IMT≥1.0mm和(或)斑塊形成)發(fā)生率(25.30%)顯著高于對(duì)照組(18.8%),差異有統(tǒng)計(jì)學(xué)意義(P0.05)。CKD3、4、5期患者頸動(dòng)脈硬化發(fā)生率分別為:20.8%、35.3%和36.7%。組間比較結(jié)果顯示,CKD5期組和CKD4期組明顯高于CKD3期組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。CKD患者頸動(dòng)脈脈內(nèi)膜中層厚度(IMT)為[0.86(0.80)mm]較對(duì)照組IMT值[0.66(0.60)mm]明顯增厚(P0.05)。CKD3、4、5期患者頸動(dòng)脈IMT分別為0.83(0.70)mm、0.85(0.80)mm、0.86(0.80)mm,其中CKD4期和CKD5期較對(duì)照組IMT值明顯增厚,差異有統(tǒng)計(jì)學(xué)意義(P值均0.05)。3 CKD患者血清PAPP-A和Hs-CRP濃度與頸動(dòng)脈硬化的關(guān)系:按照頸動(dòng)脈超聲檢測(cè)結(jié)果,分為頸動(dòng)脈正常組(IMT1.0mm)和頸動(dòng)脈硬化[IMT≥1.0mm,和(或)斑塊形成]組。CKD伴頸動(dòng)脈硬化組血清PAPP-A水平[78.28(89.45)ng/ml]較無頸動(dòng)脈硬化組[56.48(58.20)ng/ml]明顯升高(P0.01)。CKD伴頸動(dòng)脈硬化組血清Hs-CRP水平[12.91(13.63)mg/L]較無頸動(dòng)脈硬化組[10.34(10.10)mg/L]明顯升高(P0.01)。4 CKD患者血清PAPP-A水平和頸動(dòng)脈IMT與微炎癥狀態(tài)的關(guān)系:按hs-CRP水平將CKD患者分為hs-CRP≥8mg/L組和hs-CRP8mg/L組,hs-CRP≥8mg/L組PAPP-A[70.75(70.60)ng/ml]及IMT[0.89(0.80)mm]水平較hs-CRP8mg/L組[PAPP-A 35.20(35.40)ng/ml,IMT 0.76(0.70)mm]明顯升高,差異有統(tǒng)計(jì)學(xué)意義(P值均0.01)。5相關(guān)分析結(jié)果:①IMT與PAPP-A(r=0.521,P0.001)、Hs-CRP(r=0.456,P0.001)成顯著正相關(guān)。②PAPP-A與hs-CRP成正顯著相關(guān)(r=0.955,P0.01)。PAPP-A水平與血紅蛋白(r=-0.651,P0.01)、白蛋白(r=-0.4.6,P0.01)、體重指數(shù)(r=-0.564,P0.01)成負(fù)相關(guān)。PAPP-A水平收縮壓(r=0.342,P0.01)、尿素氮(r=0.7.1,P0.01)、血肌酐(r=0.666,P0.01)、血尿酸(r=0.241,P0.01)成顯著正相關(guān)。③Hs-CRP與血肌酐(r=0.689,P0.01)正相關(guān)。Hs-CR水平與與體重指數(shù)(r=-0.564,P0.001)、血紅蛋白(r=-0.721,P0.01)、白蛋白(r=-0.491,P0.01)呈負(fù)相關(guān)。收縮壓(r=0.342,P0.001)、尿素氮(r=0.752,P0.01)血肌酐(r=0.689,P0.01)、血尿酸(r=0.295,P0.01)、血甲狀旁腺激素(r=0.321,P0.01)成正相關(guān)。6多元線性回歸分析顯示:①hs-CRP(β=0.006,P0.01),PAPP-A(β=0.007,P0.001),Scr(β=0.0244,P0.05),Hb(β=0.003,P0.05)是頸動(dòng)脈IMT的顯著相關(guān)因素。結(jié)論:1 CKD患者血清PAPP-A和Hs-CRP與頸動(dòng)脈硬化密切相關(guān)。2 CKD患者血清PAPP-A是頸動(dòng)脈硬化的獨(dú)立危險(xiǎn)因子。3血清PAPP-A與Hs-CRP可能與炎癥共同參與了CKD患者動(dòng)脈粥樣硬化的發(fā)生和發(fā)展。4檢測(cè)血PAPP-A、hs-CRP濃度聯(lián)合頸動(dòng)脈超聲,可以作為判斷CKD患者動(dòng)脈粥樣硬化病變的程度的指標(biāo)。
[Abstract]:Objective: To detect the changes of serum levels of pregnancy-associated plasma protein-A (PAPP-A), high sensitive C-reactive protein (Hs-CRP) and carotid artery ultrasonography in patients with chronic kidney disease (CKD), and to analyze the relationship between PAPP-A and intima-media thickness (intima-media t) in patients with CKD. Methods: 1 Experimental group: From January 2014 to August 2014, 71 non-dialysis CKD patients, 44 males and 27 females, aged 20-68 years, with an average age of 44.95 [12.86], were enrolled in the Department of Nephrology, Second Hospital of Hebei Medical University. According to the CKD-EPI formula, the glomerular filtration rate (e GRF [ml/min/1.73m2]) was calculated and divided into CKD stage 3, CKD stage 4 and CKD stage 5 groups. There were 24 patients in CKD stage 3 group, 14 males and 10 females, aged 42.17+13.55 years, 17 patients in CKD stage 4 group, 14 males and 3 females, aged 47.44+11.31 years, 30 patients in CKD stage 5 group, 16 males and 10 females. Fourteen women, aged 46.79 [13.24], were excluded from the study. The criteria were: (1) acute infection or trauma within three months, (2) acute exacerbation of chronic renal insufficiency, (3) connective tissue disease, (4) diabetic nephropathy, (5) familial hyperlipidemia, (6) steroid or immunosuppressive therapy three months before enrollment, (7) pregnancy or childbirth, (8) acute onset within three months before enrollment. Cardiovascular and cerebrovascular events (9) Hyperuricemia. Sixteen healthy volunteers from the physical examination center of our hospital at the same time were selected as control group, including 7 males and 9 females, aged 47.31 [10.42]. 2 The concentration of PAPP-A was detected by enzyme-linked immunosorbent assay (ELISA), the concentration of Hs-CRP was determined by immunoturbidimetry, and the concentration of Hs-CRP was detected by Philips IE33 color Doppler ultrasonography. IMT and plaque were measured by echocardiograph. Two cardiac cycles were measured continuously. The mean IMT was taken as carotid IMT value. IMT 1.0 mm was normal. IMT (>1.0 mm) was regarded as early atherosclerosis. IMT (>1.2 mm) or local mixed echo or strong echo was considered as plaque formation. Blood routine, liver function and renal function were also measured. Can, blood lipids and parathyroid hormone (IPTH) and other biochemical indicators, and records of patients with general information: gender, age, primary disease, history of cardiovascular disease, blood pressure, body mass index (BMI), smoking history, etc. 3 using SPSS 13.0 software for statistical analysis of the data, taking alpha = 0.05 as the test level, with P 0.05 as the difference, on behalf of statistical significance. Results: 1 Serum PAPP-A and Hs-CRP levels in patients with CKD: The serum PAPP-A levels in patients with CKD [63.24 (62.14) ng/ml] were significantly higher than those in the control group [24.26 (22.25) ng/ml] (P 0.01). The serum PAPP-A levels in patients with CKD 3, 4 and 5 were 38.13 (38.85) ng/ml, 61.69 (61.20) ng/ml, 84.20 (88.00) ng/ml, respectively, which were significantly higher than those in the control group (P 0.05). The serum levels of Hs-CRP in CKD patients were 11.14 (12.03) mg/L and 7.17 (7.15) mg/L, 11.04 (10.98) mg/L, 14.37 (15.12) mg/L, respectively, in CKD stage 3, 4 and 5, compared with CKD control group [3.15 (3.02) mg/L] (P 0.01). The incidence of carotid atherosclerosis (IMT < 1.0mm and/or plaque formation) in CKD patients (25.30%) was significantly higher than that in CKD patients (18.8%) and the difference was statistically significant (P 0.05). The carotid atherosclerosis rate in CKD patients (P 0.01) was significantly higher than that in CKD patients (P 0.05). The incidence of carotid intima-media thickness (IMT) in CKD patients was 0.86 (0.80) mm, which was significantly thicker than that in control group (0.66 (0.60) mm). The IMT in CKD5, CKD4 and CKD3 was 0.8 mm, respectively. 3 (0.70) mm, 0.85 (0.80) mm, 0.86 (0.80) mm, in which CKD4 and CKD5 were significantly thicker than the control group IMT values, the difference was statistically significant (P values were 0.05). 3 The relationship between serum PAPP-A and Hs-CRP levels and carotid atherosclerosis in patients with CKD: According to the results of carotid ultrasonography, patients were divided into normal carotid artery group (IMT 1.0 mm) and carotid atherosclerosis [IMT < 1.0 mm, and (IMT < 1.0 mm, and < 1.0 mm The serum levels of PAPP-A in CKD patients with carotid atherosclerosis [78.28 (89.45) ng/ml] were significantly higher than those in non-carotid atherosclerosis group [56.48 (58.20) ng/ml] (P 0.01). The serum levels of Hs-CRP [12.91 (13.63) mg/L] in CKD patients with carotid atherosclerosis were significantly higher than those in non-carotid atherosclerosis group [10.34 (10.10) mg/L] (P 0.01). Relationship between carotid IMT and Micro-inflammatory state: According to hs-CRP level, CKD patients were divided into hs-CRP (> 8mg/L) group and hs-CRP 8mg/L group. The levels of PAPP-A [70.75 (70.60) ng/ml] and IMT [0.89 (0.80) mm] in hs-CRP group were significantly higher than those in hs-CRP 8mg/L group [PAPP-A 35.20 (35.40) ng/ml, IMT 0.76 (0.70) mm], with significant difference (P 0.01). Results: 1) IMT was positively correlated with PAPP-A (r = 0.521, P 0.001), Hs-CRP (r = 0.456, P 0.001) and Hs-CRP (r = 0.456, P 0.001) significantly positively correlated with PAPP-A and hs-CRP (r = 0.955, P 0.01). The levels of PAPP-A and hemoglobin (r =-0.651, P 0.01), album (r =-0.0.4.6, P 0.01, P 0.01), body mass index (r =-0.564, P 0.564, P 0.01) negatively correlwith systolic pressure (r = PAPP-A level systolic pressure (r = 0.PAPP-Urea nitrogen (r = 0.7). (3) Hs-CRP was positively correlated with sercreatinine (r = 0.689, P 0.01). Hs-CRP was positively correlated with body mass index (r = - 0.564, P 0.001), hemoglobin (r = - 0.721, P 0.01), albumin (r = - 0.721, P 0.01), albumin (r = - 0.491, P 0.01) was negatively correlwith systostolicpressure (r = 0.342, P 0.001), ureanitrogen (ureanitrogen (ureanitrogen (r = 0.001), ureanitrogen (ureanitrogen (r = 0.752, ureanitrogen (r = 0.752, ureanitrogen (r = 0.752, 0.752, 0.752 01) serum creatinine (r= Multivariate linear regression analysis showed that: (1) hs-CRP (beta = 0.006, P 0.01), PAPP-A (beta = 0.007, P 0.001), Scr (beta = 0.0244, P 0.05), Hb (beta = 0.003, IMP 0.05) were significantly correlated with carotid artery stiffness. Serum PAPP-A is an independent risk factor for carotid atherosclerosis in patients with CKD. 3 Serum PAPP-A and Hs-CRP may participate in the occurrence and development of atherosclerosis in patients with CKD together with inflammation.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R692
本文編號(hào)：2204674
[Abstract]:Objective: To detect the changes of serum levels of pregnancy-associated plasma protein-A (PAPP-A), high sensitive C-reactive protein (Hs-CRP) and carotid artery ultrasonography in patients with chronic kidney disease (CKD), and to analyze the relationship between PAPP-A and intima-media thickness (intima-media t) in patients with CKD. Methods: 1 Experimental group: From January 2014 to August 2014, 71 non-dialysis CKD patients, 44 males and 27 females, aged 20-68 years, with an average age of 44.95 [12.86], were enrolled in the Department of Nephrology, Second Hospital of Hebei Medical University. According to the CKD-EPI formula, the glomerular filtration rate (e GRF [ml/min/1.73m2]) was calculated and divided into CKD stage 3, CKD stage 4 and CKD stage 5 groups. There were 24 patients in CKD stage 3 group, 14 males and 10 females, aged 42.17+13.55 years, 17 patients in CKD stage 4 group, 14 males and 3 females, aged 47.44+11.31 years, 30 patients in CKD stage 5 group, 16 males and 10 females. Fourteen women, aged 46.79 [13.24], were excluded from the study. The criteria were: (1) acute infection or trauma within three months, (2) acute exacerbation of chronic renal insufficiency, (3) connective tissue disease, (4) diabetic nephropathy, (5) familial hyperlipidemia, (6) steroid or immunosuppressive therapy three months before enrollment, (7) pregnancy or childbirth, (8) acute onset within three months before enrollment. Cardiovascular and cerebrovascular events (9) Hyperuricemia. Sixteen healthy volunteers from the physical examination center of our hospital at the same time were selected as control group, including 7 males and 9 females, aged 47.31 [10.42]. 2 The concentration of PAPP-A was detected by enzyme-linked immunosorbent assay (ELISA), the concentration of Hs-CRP was determined by immunoturbidimetry, and the concentration of Hs-CRP was detected by Philips IE33 color Doppler ultrasonography. IMT and plaque were measured by echocardiograph. Two cardiac cycles were measured continuously. The mean IMT was taken as carotid IMT value. IMT 1.0 mm was normal. IMT (>1.0 mm) was regarded as early atherosclerosis. IMT (>1.2 mm) or local mixed echo or strong echo was considered as plaque formation. Blood routine, liver function and renal function were also measured. Can, blood lipids and parathyroid hormone (IPTH) and other biochemical indicators, and records of patients with general information: gender, age, primary disease, history of cardiovascular disease, blood pressure, body mass index (BMI), smoking history, etc. 3 using SPSS 13.0 software for statistical analysis of the data, taking alpha = 0.05 as the test level, with P 0.05 as the difference, on behalf of statistical significance. Results: 1 Serum PAPP-A and Hs-CRP levels in patients with CKD: The serum PAPP-A levels in patients with CKD [63.24 (62.14) ng/ml] were significantly higher than those in the control group [24.26 (22.25) ng/ml] (P 0.01). The serum PAPP-A levels in patients with CKD 3, 4 and 5 were 38.13 (38.85) ng/ml, 61.69 (61.20) ng/ml, 84.20 (88.00) ng/ml, respectively, which were significantly higher than those in the control group (P 0.05). The serum levels of Hs-CRP in CKD patients were 11.14 (12.03) mg/L and 7.17 (7.15) mg/L, 11.04 (10.98) mg/L, 14.37 (15.12) mg/L, respectively, in CKD stage 3, 4 and 5, compared with CKD control group [3.15 (3.02) mg/L] (P 0.01). The incidence of carotid atherosclerosis (IMT < 1.0mm and/or plaque formation) in CKD patients (25.30%) was significantly higher than that in CKD patients (18.8%) and the difference was statistically significant (P 0.05). The carotid atherosclerosis rate in CKD patients (P 0.01) was significantly higher than that in CKD patients (P 0.05). The incidence of carotid intima-media thickness (IMT) in CKD patients was 0.86 (0.80) mm, which was significantly thicker than that in control group (0.66 (0.60) mm). The IMT in CKD5, CKD4 and CKD3 was 0.8 mm, respectively. 3 (0.70) mm, 0.85 (0.80) mm, 0.86 (0.80) mm, in which CKD4 and CKD5 were significantly thicker than the control group IMT values, the difference was statistically significant (P values were 0.05). 3 The relationship between serum PAPP-A and Hs-CRP levels and carotid atherosclerosis in patients with CKD: According to the results of carotid ultrasonography, patients were divided into normal carotid artery group (IMT 1.0 mm) and carotid atherosclerosis [IMT < 1.0 mm, and (IMT < 1.0 mm, and < 1.0 mm The serum levels of PAPP-A in CKD patients with carotid atherosclerosis [78.28 (89.45) ng/ml] were significantly higher than those in non-carotid atherosclerosis group [56.48 (58.20) ng/ml] (P 0.01). The serum levels of Hs-CRP [12.91 (13.63) mg/L] in CKD patients with carotid atherosclerosis were significantly higher than those in non-carotid atherosclerosis group [10.34 (10.10) mg/L] (P 0.01). Relationship between carotid IMT and Micro-inflammatory state: According to hs-CRP level, CKD patients were divided into hs-CRP (> 8mg/L) group and hs-CRP 8mg/L group. The levels of PAPP-A [70.75 (70.60) ng/ml] and IMT [0.89 (0.80) mm] in hs-CRP group were significantly higher than those in hs-CRP 8mg/L group [PAPP-A 35.20 (35.40) ng/ml, IMT 0.76 (0.70) mm], with significant difference (P 0.01). Results: 1) IMT was positively correlated with PAPP-A (r = 0.521, P 0.001), Hs-CRP (r = 0.456, P 0.001) and Hs-CRP (r = 0.456, P 0.001) significantly positively correlated with PAPP-A and hs-CRP (r = 0.955, P 0.01). The levels of PAPP-A and hemoglobin (r =-0.651, P 0.01), album (r =-0.0.4.6, P 0.01, P 0.01), body mass index (r =-0.564, P 0.564, P 0.01) negatively correlwith systolic pressure (r = PAPP-A level systolic pressure (r = 0.PAPP-Urea nitrogen (r = 0.7). (3) Hs-CRP was positively correlated with sercreatinine (r = 0.689, P 0.01). Hs-CRP was positively correlated with body mass index (r = - 0.564, P 0.001), hemoglobin (r = - 0.721, P 0.01), albumin (r = - 0.721, P 0.01), albumin (r = - 0.491, P 0.01) was negatively correlwith systostolicpressure (r = 0.342, P 0.001), ureanitrogen (ureanitrogen (ureanitrogen (r = 0.001), ureanitrogen (ureanitrogen (r = 0.752, ureanitrogen (r = 0.752, ureanitrogen (r = 0.752, 0.752, 0.752 01) serum creatinine (r= Multivariate linear regression analysis showed that: (1) hs-CRP (beta = 0.006, P 0.01), PAPP-A (beta = 0.007, P 0.001), Scr (beta = 0.0244, P 0.05), Hb (beta = 0.003, IMP 0.05) were significantly correlated with carotid artery stiffness. Serum PAPP-A is an independent risk factor for carotid atherosclerosis in patients with CKD. 3 Serum PAPP-A and Hs-CRP may participate in the occurrence and development of atherosclerosis in patients with CKD together with inflammation.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R692
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相關(guān)期刊論文 前2條
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