【作者】 祝俊琪；

【导师】 李绍梅；

【作者基本信息】 河北医科大学 ， 内科学， 2008， 硕士

【摘要】 目的:1.探讨慢性肾脏病(CKD)患者血清瘦素和C-反应蛋白浓度的改变;2.探讨慢性肾脏病患者颈动脉内膜-中层厚度(IMT)的变化;3.探讨慢性肾脏病患者血清瘦素水平与C-反应蛋白水平及临床各指标之间的关系;4.探讨慢性肾脏病患者血清瘦素和C-反应蛋白与颈动脉IMT的相关性和两者在动脉粥样硬化发生中的可能机制。方法:收集我科住院的CKD患者79例,男51例,女28例,平均年龄44.22±13.47岁。CKD诊断标准参照K/DOQI指南[1]。原发病包括:慢性肾小球肾炎58例、多囊肾3例、梗阻性肾病6例、慢性小管间质性肾炎5例、病因不明7例。按照GFR水平分为3组: (1)CKD2~3期26例(GFR30~89ml/min/1.73m2),其中男性18例,女性8例,平均年龄44.69±14.13岁;(2)CKD4期22例(GFR15~29 ml/min/1.73m2),其中男性16例,女性6例,平均年龄42.7±12.63岁;(3)CKD5期31例(GFR<15ml /min/1.73m2),其中男性17例,女性14例,平均年龄45.19±13.78岁;(4)健康对照组13例,其中男性8例,女性5例,平均年龄40.07±18.51岁。排除标准:①近1个月内感染、手术、创伤者;②近1个月发生过急性心血管事件者;③近六个月内使用过激素和免疫抑制剂者;④合并恶性肿瘤、妊娠者;⑤糖尿病肾病;⑥进入透析的患者或者肾移植患者。所有受试者于清晨空腹卧位抽取肘静脉血6ml,应用全自动生化分析仪测定常规生化指标,其中包括同时测定临床生化指标,其中包括血常规(Rt)、血清肌酐(Scr)、尿素氮(BUN)、血糖、总胆固醇(Chol)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、极低密度脂蛋白(VLDL)、血清总蛋白(TP)和白蛋白(Alb)。同时离心分离血清,置-70℃保存备检,用时冰融,集中测定瘦素和CRP。血清瘦素(leptin)浓度测定应用放射免疫分析法,血清高敏CRP(hs-CRP)采用免疫透射比浊法。采用高分辨超声技术测颈动脉内膜-中层厚度(IMT)及粥样硬化斑块。计算体质量指数(BMI)[BMI=体质量(kg)/身高(m)2]和肾小球滤过率(GFR)。结果:1.慢性肾脏病患者的血清瘦素水平(14.86±5.92 ng/L)明显高于健康对照组(8.72±2.35ng/m1)p<0.01,且随肾功能恶化逐渐升高(CKD2~3期:12.0±2.56ng/ml;CKD4期:14.98±5.69ng/ml;CKD5期:19.78±5.23ng/ml)。慢性肾脏病患者的血清C-反应蛋白水平(2.65±1.32mg/L)明显高于健康对照组(1.52±0.88mg/L) p<0.01,且随肾功能恶化逐渐升高(CKD2~3期:1.85±0.86mg/L;CKD4期:2.96±0.99mg/L;CKD5期:3.55±1.26 mg/L);2.慢性肾脏病患者的颈动脉IMT水平(0.953±0.256mm)明显高于健康对照组(0.675±0.249mm)p<0.01,且随肾功能恶化逐渐升高(CKD2~3期:0.681±0.172mm;CKD4期:0.814±0.173mm;CKD5期:0.932±0.156mm);3.慢性肾脏病患者颈动脉超声异常组(IMT增厚:颈总动脉IMT≥0.9mm,或分叉处IMT>0.9mm;粥样斑块:突向管腔的局灶性动脉壁增厚,其厚度超过相邻区域IMT至少50%)血清瘦素水平(17.06±1.06ng/ml)和CRP水平(3.32±0.19mg/L)较颈动脉正常组血清瘦素水平(14.27±0.70ng/ml)和CRP(2.55±0.17mg/L)明显升高;4.慢性肾脏病患者高CRP组血清瘦素水平(18.78±5.52ng/ml)和颈动脉IMT(0.79±0.19mm)较CRP正常组血清瘦素水平(14.20±5.17ng/ml)和颈动脉IMT(0.70±0.15mm)明显升高;5.慢性肾脏病患者高瘦素组血清CRP水平(3.66±0.21mg/L)和颈动脉IMT(0.79±0.133mm)较低瘦素组血清CRP水平(2.24g±0.14mg/L)和颈动脉(0.71±0.054mm)明显升高(P<0.05);6.慢性肾脏病患者存在营养不良者(ALB<35g/L)血清瘦素水平(16.67±0.93ng/ml)、血清C-反应蛋白浓度(3.14±0.21mg/L)和颈动脉IMT(0.760±0.273 mm)较ALB≥35g/L组血清瘦素水平(14.17±0.75ng/ml)、血清C-反应蛋白浓度(2.49±0.19mg/L)和颈动脉IMT(0.716±0.273mm)明显升高;7.慢性肾脏病患者的血清瘦素水平与临床各项指标的直线相关分析显示:①血清瘦素与尿素氮、肌酐、C-反应蛋白、体重指数之间呈显著正相关(r=0.293,P<0.01;r=0.324,P<0.01;r=0.539,P<0.01;r=0.312,P<0.05);②血清瘦素与肾小球滤过率、血红蛋白、ALB之间呈明显负相关(r=-0.389,P<0.01;r=-0.454,P<0.01;r=-0.246, P<0.05),与年龄、Chol、TG无明显相关性(r=0.014, P>0.05;r=0.051, P>0.05;r=-0.055, P>0.05);8.多元线性回归分析显示:CKD患者颈动脉IMT与血清瘦素、C-反应蛋白、甘油三脂、血红蛋白密切相关(β=0.546,P<0.01;β=0.386,P<0.05;β=0.791,P<0.05;β=0.532,P<0.01),提示血浆瘦素与C-反应蛋白直接参与了动脉粥样硬化、粥样斑块的形成;9. Logistic逐步回归分析显示:瘦素(β=1.527,95%CI:1.028~1.438,P<0.05)是CKD患者并发动脉粥样硬化的独立危险因素之一。结论:①慢性肾脏病患者存在高瘦素血症和微炎症状态,②高瘦素血症与微炎症状态和慢性肾脏病患者高发动脉粥样硬化性心血管事件相关;③血清瘦素可能微炎症反应相互作用而参与了慢性肾脏病患者动脉粥样硬化的形成。更多还原

【Abstract】 Objective : 1.To investigate the changes of the concentration of serum leptin and C-reaction protein (CRP) with chronic kidney disease (CKD);2.To investigate the changes of the level of IMT of carotid artery with chronic kidney disease(CKD);3.To investigate the relationship between the level of the serum leptin , C-reaction protein (CRP) and each of the parameter for clinic with chronic kidney disease (CKD);4.To explore the relationship among the serum leptin, C-reaction protein (CRP) and chronic kidney disease (CKD),and the possible mechanism of leptin to atherosclerosis seen in chronic kidney disease (CKD).Methods:We collected 79 patients with chronic kidney disease (51 males and 28 females) aged 44.22±13.47 (mean±SD). The standard of diagnosis by using K/DOQI guideline[1]. The primary diseases: 53 patients were chronic glomerulo- nephritis, 5 patients were hypertention nephritis, 3 patients were polycystic kidney,4 patients were obstructive nephropathy and 12 patients were etiology unknown. 79 patients with chronic kidney disease were classified into three groups according to glomerular filtration rate (GFR): (1) CKD2~3 stage groups included 26 patients (GFR30~90ml/min /1.73m2), (18 males and 8 females),the average age is 44.69±14.13 years; (2) CKD4 stage groups included 22 patients (GFR15~30ml/min/1.73m2), (16 males and 6 females),the average age is 42.7±12.63 years;(3) CKD 5stage groups included 31 patients (GFR<15ml/min /1.73m2), (17 males and 14 females),the average age is 45.19±13.78 years;(4) Healthy control group included 13 healthy volunteers (8 males and 5 females), aged 40.07±18.51 (mean±SD). Excluding standards:①Those who were infected, operated on and had trauma in recently one month;②To have acute cardiovascular disease (CVD) in recently one month;③Those who have used the cortical hormone or other immunity conditioner in recently six months ;④To affiliate malignancy, pregnancy;⑤diabetic nephropathy;⑥To have dialysis or renal transplantation. All the patients starved for 12 hours and the vein blood 6ml was sampled in the morning. The blood samples were tested by the automatic biochemical machine to measure the blood routine, blood creatinine, urea nitrogen, blood sugar, the cholesterol, triglyceride, high dense lipoprotein cholesterol, low dense lipoprotein, very low density lipoproteintotal protein, albumin. At the same time, the serum was centrifugally separated and saved in -70℃refrigerator to measure the leptin and CRP, The leptin was tested by the radio-immunity method and the reagents were provided by the Beijing Puer Weiye Biotechnical Institute. The CRP was tested by the rate-scatter turbidimetry method and the antiserum was provided by Shanghai Sun Biotechnical Institute. Seventy nine CKD patients and 13 healthy volunteers were involved in the study. The serum leptin was tested by the radio-immunity method;The CRP was tested by the rate-scatter turbidimetry method. Intima-medial thickness (IMT) of extracranial common carotid artery and the presence of atherosclerotic plaques were determined by using noninvasive high-resolution B-mode ultrasonography. To calculate body mass index (BMI) and glomerular filtration rate (GFR).Results:1. Levels of leptin in the chronic kidney disease (CKD) patients were significantly higher than those in the healthy groups, and to elevate along with the deteriorate of kidney function;Levels of CRP in the chronic kidney disease (CKD) patients were significantly higher than those in the healthy groups, and to elevate along with the deterioration of kidney function;2. The IMT in carotid artery were significantly higher in CKD patients compared with the healthy groups, and to elevate along with the deteriorate of kidney function;3. It was found that patients with chronic kidney disease in the high IMT of carotid artery groups had serum CRP and serum leptin concentrations significantly increased compared with the normal IMT of carotid artery groups;4. It was found that patients with chronic kidney disease in the high CRP groups had serum leptin concentrations and IMT of carotid artery significantly increased compared with the normal CRP groups;5. It was found that patients with chronic kidney disease in hyperleptin groups had serum CRP concentrations and IMT of carotid artery significantly increased compared with the lowleptin groups; 6. It was found that patients with chronic kidney disease in the Alb <35g/L groups had serum CRP concentrations and IMT of carotid artery significantly increased compared with the Alb >35g/L groups;7. The linear correlations were found between the leptin and parameters in patients with chronic kidney disease (CKD) as follows:①The serum leptin levels were correlated positively with urea nitrogen serum creatinine C-reaction body mass index (BMI) (r=0.293,P<0.01;r=0.324,P<0.01;r=0.539,P<0.01;r=0.312,P<0.05);②The serum leptin levels were correlated negatively with glomerular filtration rate hemoglobin albumin (r=-0.389,P<0.01;r=-0.454,P<0.01;r=-0.246, P< 0.05),and were not correlated with age cholesterol triglyceride (r=0.014, P>0.05;r=0.051, P>0.05;r=-0.055, P>0.05) 8.The linear correlation regression analyses for IMT and serum leptin, serum CRP, TG, Hb, showed that serum leptin and serum CRP participated straightly in the atherosclerosis of vessel and the forming of atherosclerosis spot mass. 9. Logistic regression analysis further indicated that Leptin (β=1.527, 95%CI :1.028~1.438 , P<0.05) was an independent risk factor of atherosclerosis-related cardiovascular events in chronic disease (CKD).Conclusions:①There is hyperleptin and micro inflamma- tory state in the chronic kidney disease (CKD) patients.②The leptin and microinflammatory state might be in close correlation with atherosclerosis-related cardiovascular events in chronic kidney disease (CKD).③The serum leptin and microinflamma- tion may result in accelerated atherosclerosis seen in chronic kidney disease (CKD).更多还原