高通量透析对维持性血液透析患者晚期氧化蛋白产物的影响
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摘要
研究背景
氧化应激(oxidative stress, OS)在肾脏疾病进展及其并发症中的作用十分重要,尤其是已进入血液透析的患者。减轻维持性血液透析(maintenance hemodialysis, MHD)患者的氧化应激状态,可能直接关系到透析患者的远期生存质量。晚期氧化蛋白产物(advanced oxidation protein products, AOPPs)是体内白蛋白与次氯酸氧化的产物,是氧化介导的蛋白质损伤的重要标志物。AOPPs是一个直接涉及到调控生理活动的蛋白质的氧化应激指标,无论在评价氧化应激的特异性、灵敏性、治疗预后还是在检测方法运用的简便性、普及性方面,AOPPs也优于其他一些经典的检测指标如丙二醛(malondialdehyde, MDA)等。研究显示AOPPs除了可作为氧化应激的指标外,它在慢性肾衰患者病理生理及透析相关并发症的发生发展中起着重要作用,特别是其与尿毒症心血管疾病的关系更加引人注目。国内外很多学者对于如何降低AOPPs水平,减轻氧化应激状态进行了研究,但关于高通量透析对于AOPPs水平影响的报道不多。本研究以MHD患者为研究对象,检测其血浆AOPPs水平及其他生化指标,以期探讨AOPPs的相关影响因素,并探讨高通量透析对AOPPs水平的影响。
方法
采用分光光度计方法对103例MHD患者(MHD组)及20例入组MHD患者(试验组)和50例慢性肾脏病(chronic kidney disease, CKD)5期未透析患者(CKD组)及31例健康志愿者(对照组)进行血浆AOPPs测定,MHD组患者同时进行血生化指标等检查,收集其临床基本资料。试验组患者先行普通低通量透析3个月(low-flux hemodialysis, LFHD),后改为高通量透析(high-flux hemodialysis, HFHD)3个月,研究间期共6个月。先后检测0、3、6个月末时透析前后血浆AOPPs水平及部分血生化指标,并分别检测单次HFHD、LFHD透析时透析液中AOPPs水平。所有计量资料均采用x±s表示,统计学处理采用SPSS12.0统计软件包,两组间连续变量的比较采用两独立样本t检验,多组间连续变量的比较采用单因素方差分析,组间比较采用SNK法(q检验)。AOPPs与其它指标的相关分析采用Pearson法。多元回归通过逐步多元线性回归分析。以P<0.05认为差异具有统计学意义。
结果
1.MHD组患者血浆AOPPs水平明显高于对照组及CKD组(P=0.000)。CKD组患者血浆AOPPs水平明显高于对照组(P=0.041)。
2.将MHD组患者血浆AOPPs水平分别与患者的白蛋白(ALB)、血红蛋白(HGB)、血肌酐(Cr)、尿酸(UA)、甘油三酯(TG)、胆固醇(CHO)、血钙(Ca)、血磷(P)等生化指标及年龄、透析龄、原发病、是否应用ACEI等临床资料作相关性分析。结果显示：AOPPs与甘油三酯(r=0.701,P=0.000)、肌酐(r=0.310,P=0.002)、钙(r=0.254,P=0.011)、白蛋白(r=0.236,P=0.019)呈正相关,与其它指标均无相关性。多元逐步回归分析显示,TG、Cr、Ca为AOPPs的高危因素,回归方程为AOPPs=10.070×TG+0.012×Cr+13.437×Ca-12.037
3.试验组患者序贯进行3个月LFHD后改为HFHD3个月(即：0～3个月为LFHD,3～6个月为HFHD),检测0、3、6个月末时透析前后血浆AOPPs水平及其他部分生化指标,3个月时AOPPs水平较前有下降趋势,但并无统计学意义(42.94±18.70vs39.56±16.09umol/L, P=0.418)。6个月时AOPPs水平较前下降明显,差异有统计学意义(39.56±16.09 vs 30.09±8.39 umol/L, P=0.000),无论是LFHD还是HFHD,单次透析后AOPPs水平均较透前有升高,差异均有统计学意义(LFHD透析前后分别为42.94±18.70 vs 68.47±46.00 umol/L, P=0.000; HFHD透析前后分别为39.56±16.09vs78.14±38.90 umol/L, P=0.014)
4.3个月时血脂水平有上升,但无统计学意义(1.70±0.94 vs 1.72±0.91umol/L P=0.851)。6个月时血脂水平较3个月时有下降,差异有统计学意义(1.72±0.91 vs 1.43±0.54umol/L, P=0.037)。
结论
1.慢性肾脏病5期患者普遍存在AOPPs水平明显升高,已进入血液透析的患者AOPPs水平明显高于未透析患者。
2.维持性血液透析患者血浆AOPPs值与甘油三酯、肌酐、钙、白蛋白呈正相关,与其它指标均无相关性。多元逐步回归分析显示,甘油三酯、肌酐、钙为AOPPs的高危因素。
3.血液透析过程不能清除AOPPs,且增加AOPPs水平,但长期高通量透析可以降低维持性血液透析患者的AOPPs水平,可能与血脂等方面的改善有关。
Background:Oxidative stress (OS) is very important in the progressment and complication of renal disease,particularly for those patients in maintenance hemodialysis. To relieave the oxidative state of those patients in maintenance hemodialysis may regard to the survival quality at a long term. Advanced oxidation protein products (AOPPs) are the oxidative products of albumin and hypochlorous acid, and it is an important marker for the damages of the protein through oxidation introduction. AOPPs as an important indicator of oxidation refer to albumin are superior to those classical indicator such as malondialdehyde (MDA), not only in the specificity and sensitivity of estimation, but also in the portability and popularity of detectation. Researches have shown that AOPPs not only act as an indicator for oxidative stress but also play an important role in the occurrence and development of pathological, physiological and dialysis-related complications of CKD patients. And their relation with CVD attracts our attention. Many researches approach how to lessen the level of AOPPs and alleviate the OS state of patients, but few researches are about the high-flux hemodialysis. Based on the study of MHD patients by means of determining the AOPPs levels and biochemical indicators, this research is expected to investigate the related affecting factors of plasma AOPPs and the influenc of HFHD on the level of AOPPs.
Methods:Plasma AOPPs of MHD group、observed group、CKD group and control group are tested.And for observed group and MHD group, biochemical indicators are tested and the clinical basical data such as age, hemodialysis stage, primary disease and drug prescription are collected.For observed group, three months LFHD sequential three months HFHD are performed.This research lasts six months. Plasma AOPPs and other biochemical indicators are tested at 0 month, the 3th month, the 6th month. The statistical processes are conducted through SPSS12.0. The comparisons between the variables are made by t test. The comparisons among three variables are made by one-way ANOVA. The correlation analysis is made by Pearson method. Multi-regression analysis is made by means of multiple linear stepwise regressions. The differences are considered to be statistically significant when P<0.05.
Results:(1) The plasma AOPPs level of the MHD group is obviously higher than the CKD group and control group (P=0.000),and CKD group is higher than the control group.(2) Correlation analysis are performed between the serum AOPPs level of MHD with other indicators such as albumin、hemoglobin、serum creatinine、uric acid、triglyceride、cholesterin、calcium、phosphorus、age、hemodialysis time,etc.The result shows that positive correlation exists between AOPPs level with triglyceride (r =0.701, P=0.000)、calcium (r=0.254, P=0.011), creatinine(r=0.310,P=0.002) and albumin(r=0.236, P=0.019). Multiple linear stepwise regressions analysis shows that triglyceride、calcium、creatinine are the independently risk factors of AOPPs level. Regression equation is AOPPs=10.070xTG+0.012xCr+13.437xCa-12.037.(3)Three months LFHD sequential three months HFHD are performed for twenty patients, then the plasma AOPPs level and other biochemical indicators are tested at 3rd month and 6th month. There is a downturn in LFHD, but no statistically significant (42.94±18.70v,s39.56±16.09umol/L, P=0.418).And there is a statistically significant in HFHD (39.56±16.09 vs 30.09±8.39 umol/L, P=0.000). The plasma AOPPs level rise after one dialysis.(4) There is a uptrend in triglyceride after three months LFHD,but no statistically significant (1.70±0.94 vs 1.72±0.91,P=0.851). There is a statistically significant downturn in HFHD (1.72±0.91 vs 1.43±0.54, P=0.037)
Conclusion:1. CKD 5 stage patients generally have higher AOPPs levels generally,and patients in maintenance hemodialysis have higher AOPPs level than Non-dialytic CKD patients 2. Correlation analysis showes that AOPPs level has positive correlation with triglyceride、calcium、creatinine、and albumin,but no correlation with other indicators. multiple linear stepwise regressions analysis shows that triglyceride、calcium、creatinine are the independently risk factors of AOPPs level.3. Every hemodialysis may increase AOPPs level, but long-term HFHD can ameliorate AOPPs level and TG level.This may be regard to the improvement of triglyceride and inflammation.
氧化应激(oxidative stress, OS)在肾脏疾病进展及其并发症中的作用十分重要,尤其是已进入血液透析的患者。减轻维持性血液透析(maintenance hemodialysis, MHD)患者的氧化应激状态,可能直接关系到透析患者的远期生存质量。晚期氧化蛋白产物(advanced oxidation protein products, AOPPs)是体内白蛋白与次氯酸氧化的产物,是氧化介导的蛋白质损伤的重要标志物。AOPPs是一个直接涉及到调控生理活动的蛋白质的氧化应激指标,无论在评价氧化应激的特异性、灵敏性、治疗预后还是在检测方法运用的简便性、普及性方面,AOPPs也优于其他一些经典的检测指标如丙二醛(malondialdehyde, MDA)等。研究显示AOPPs除了可作为氧化应激的指标外,它在慢性肾衰患者病理生理及透析相关并发症的发生发展中起着重要作用,特别是其与尿毒症心血管疾病的关系更加引人注目。国内外很多学者对于如何降低AOPPs水平,减轻氧化应激状态进行了研究,但关于高通量透析对于AOPPs水平影响的报道不多。本研究以MHD患者为研究对象,检测其血浆AOPPs水平及其他生化指标,以期探讨AOPPs的相关影响因素,并探讨高通量透析对AOPPs水平的影响。
方法
采用分光光度计方法对103例MHD患者(MHD组)及20例入组MHD患者(试验组)和50例慢性肾脏病(chronic kidney disease, CKD)5期未透析患者(CKD组)及31例健康志愿者(对照组)进行血浆AOPPs测定,MHD组患者同时进行血生化指标等检查,收集其临床基本资料。试验组患者先行普通低通量透析3个月(low-flux hemodialysis, LFHD),后改为高通量透析(high-flux hemodialysis, HFHD)3个月,研究间期共6个月。先后检测0、3、6个月末时透析前后血浆AOPPs水平及部分血生化指标,并分别检测单次HFHD、LFHD透析时透析液中AOPPs水平。所有计量资料均采用x±s表示,统计学处理采用SPSS12.0统计软件包,两组间连续变量的比较采用两独立样本t检验,多组间连续变量的比较采用单因素方差分析,组间比较采用SNK法(q检验)。AOPPs与其它指标的相关分析采用Pearson法。多元回归通过逐步多元线性回归分析。以P<0.05认为差异具有统计学意义。
结果
1.MHD组患者血浆AOPPs水平明显高于对照组及CKD组(P=0.000)。CKD组患者血浆AOPPs水平明显高于对照组(P=0.041)。
2.将MHD组患者血浆AOPPs水平分别与患者的白蛋白(ALB)、血红蛋白(HGB)、血肌酐(Cr)、尿酸(UA)、甘油三酯(TG)、胆固醇(CHO)、血钙(Ca)、血磷(P)等生化指标及年龄、透析龄、原发病、是否应用ACEI等临床资料作相关性分析。结果显示：AOPPs与甘油三酯(r=0.701,P=0.000)、肌酐(r=0.310,P=0.002)、钙(r=0.254,P=0.011)、白蛋白(r=0.236,P=0.019)呈正相关,与其它指标均无相关性。多元逐步回归分析显示,TG、Cr、Ca为AOPPs的高危因素,回归方程为AOPPs=10.070×TG+0.012×Cr+13.437×Ca-12.037
3.试验组患者序贯进行3个月LFHD后改为HFHD3个月(即：0～3个月为LFHD,3～6个月为HFHD),检测0、3、6个月末时透析前后血浆AOPPs水平及其他部分生化指标,3个月时AOPPs水平较前有下降趋势,但并无统计学意义(42.94±18.70vs39.56±16.09umol/L, P=0.418)。6个月时AOPPs水平较前下降明显,差异有统计学意义(39.56±16.09 vs 30.09±8.39 umol/L, P=0.000),无论是LFHD还是HFHD,单次透析后AOPPs水平均较透前有升高,差异均有统计学意义(LFHD透析前后分别为42.94±18.70 vs 68.47±46.00 umol/L, P=0.000; HFHD透析前后分别为39.56±16.09vs78.14±38.90 umol/L, P=0.014)
4.3个月时血脂水平有上升,但无统计学意义(1.70±0.94 vs 1.72±0.91umol/L P=0.851)。6个月时血脂水平较3个月时有下降,差异有统计学意义(1.72±0.91 vs 1.43±0.54umol/L, P=0.037)。
结论
1.慢性肾脏病5期患者普遍存在AOPPs水平明显升高,已进入血液透析的患者AOPPs水平明显高于未透析患者。
2.维持性血液透析患者血浆AOPPs值与甘油三酯、肌酐、钙、白蛋白呈正相关,与其它指标均无相关性。多元逐步回归分析显示,甘油三酯、肌酐、钙为AOPPs的高危因素。
3.血液透析过程不能清除AOPPs,且增加AOPPs水平,但长期高通量透析可以降低维持性血液透析患者的AOPPs水平,可能与血脂等方面的改善有关。
Background:Oxidative stress (OS) is very important in the progressment and complication of renal disease,particularly for those patients in maintenance hemodialysis. To relieave the oxidative state of those patients in maintenance hemodialysis may regard to the survival quality at a long term. Advanced oxidation protein products (AOPPs) are the oxidative products of albumin and hypochlorous acid, and it is an important marker for the damages of the protein through oxidation introduction. AOPPs as an important indicator of oxidation refer to albumin are superior to those classical indicator such as malondialdehyde (MDA), not only in the specificity and sensitivity of estimation, but also in the portability and popularity of detectation. Researches have shown that AOPPs not only act as an indicator for oxidative stress but also play an important role in the occurrence and development of pathological, physiological and dialysis-related complications of CKD patients. And their relation with CVD attracts our attention. Many researches approach how to lessen the level of AOPPs and alleviate the OS state of patients, but few researches are about the high-flux hemodialysis. Based on the study of MHD patients by means of determining the AOPPs levels and biochemical indicators, this research is expected to investigate the related affecting factors of plasma AOPPs and the influenc of HFHD on the level of AOPPs.
Methods:Plasma AOPPs of MHD group、observed group、CKD group and control group are tested.And for observed group and MHD group, biochemical indicators are tested and the clinical basical data such as age, hemodialysis stage, primary disease and drug prescription are collected.For observed group, three months LFHD sequential three months HFHD are performed.This research lasts six months. Plasma AOPPs and other biochemical indicators are tested at 0 month, the 3th month, the 6th month. The statistical processes are conducted through SPSS12.0. The comparisons between the variables are made by t test. The comparisons among three variables are made by one-way ANOVA. The correlation analysis is made by Pearson method. Multi-regression analysis is made by means of multiple linear stepwise regressions. The differences are considered to be statistically significant when P<0.05.
Results:(1) The plasma AOPPs level of the MHD group is obviously higher than the CKD group and control group (P=0.000),and CKD group is higher than the control group.(2) Correlation analysis are performed between the serum AOPPs level of MHD with other indicators such as albumin、hemoglobin、serum creatinine、uric acid、triglyceride、cholesterin、calcium、phosphorus、age、hemodialysis time,etc.The result shows that positive correlation exists between AOPPs level with triglyceride (r =0.701, P=0.000)、calcium (r=0.254, P=0.011), creatinine(r=0.310,P=0.002) and albumin(r=0.236, P=0.019). Multiple linear stepwise regressions analysis shows that triglyceride、calcium、creatinine are the independently risk factors of AOPPs level. Regression equation is AOPPs=10.070xTG+0.012xCr+13.437xCa-12.037.(3)Three months LFHD sequential three months HFHD are performed for twenty patients, then the plasma AOPPs level and other biochemical indicators are tested at 3rd month and 6th month. There is a downturn in LFHD, but no statistically significant (42.94±18.70v,s39.56±16.09umol/L, P=0.418).And there is a statistically significant in HFHD (39.56±16.09 vs 30.09±8.39 umol/L, P=0.000). The plasma AOPPs level rise after one dialysis.(4) There is a uptrend in triglyceride after three months LFHD,but no statistically significant (1.70±0.94 vs 1.72±0.91,P=0.851). There is a statistically significant downturn in HFHD (1.72±0.91 vs 1.43±0.54, P=0.037)
Conclusion:1. CKD 5 stage patients generally have higher AOPPs levels generally,and patients in maintenance hemodialysis have higher AOPPs level than Non-dialytic CKD patients 2. Correlation analysis showes that AOPPs level has positive correlation with triglyceride、calcium、creatinine、and albumin,but no correlation with other indicators. multiple linear stepwise regressions analysis shows that triglyceride、calcium、creatinine are the independently risk factors of AOPPs level.3. Every hemodialysis may increase AOPPs level, but long-term HFHD can ameliorate AOPPs level and TG level.This may be regard to the improvement of triglyceride and inflammation.
引文
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[27]Descamps-Latscha -B, Jungers -P, Witko-Sarsat -V. Immune system dysregulation in uremia:Role of oxidative stress [J]. Blood-Purif, 2002,20(5):481-484
[28]Capeillere-Blandin C, Gausson V, Descamps-Latscha B, et al. Biochemical and spectrophotometric significance of advanced oxidized protein products [J]. Biochim Biophys Acta,2004,1689(2):91-102
[29]丁峰,朱秋毓,顾勇,等.高级氧化蛋白产物的主要成份分析[J].中华肾脏病杂志,2006,22(1)33-36
[30]Himmelfarb J, McMonagle E. Albumin is the major plasma protein target of oxidant stress in the uriemia [J]. Kidney Int,2001,60:358-363
[31]Witko-Sarsat V, Friedlander M, Nguyen-Khoa, et al. Advanced oxidation protein products as a novel mediator of inflammation and monocyte activation in chronic renal failure [J]. J Immunal,1998,161(5):2524-32
[32]Drueke T, Witko-Sarsat V, Massy Z, et al. Iron therapy, Advanced oxidation protein products, and caroid artery intima-media thickness in end-stage renal disease[J]. Circulation,2002,106(17):2212-2217.
[33]Wratten ML, Tetta C, Ursini F, et al. Oxidant stress in hemodialysis:Prevention and treatment strategies [J]. Kidney Int,2000,76; S126-32
[34]Kalousova M, Skrha J, Zima T. Advanced glycation end-products and advanced protein products in patients with diabetes mellitus[J]. Physiol Res,2002, 51(6):597-604
[35]刘永军,祝立志,欧列斌,等.维持性血液透析患者氧化应激水平及其影响因素分析.海南医学,2005,16(2)10-11.
[36]杨小兵,侯凡凡,武强等.慢性肾脏病患者晚期氧化蛋白产物血症及其与动脉粥样硬化的关系[J].中华内科杂志,2005,44(5)：342-346
[37]Kaneda H. Taguchi J, Ogasawara K, et al. Increased level of advanced oxidation protein products in patients with coronary artery disease[J]. Athemsclemsis,2002,162: 221-225.
[38]唐子勇,阿拉塔,朱宁,等.血液透析患者氧化应激水平及其相关因素分析.临床内科杂志,2004,21(4)：252-254
[39]刘晓燕,钟一红,陈利明,等.慢性肾脏病时的氧化应激评价指标研究.中国临床医学,2010,17(5)：623-626
[40]Appel GLipid abnormalities in renal disease.Kidney Int.1991; 39(1):169-183
[41]Vaziri ND.Causes of dysregulation of lipid metabolism in chronic renal failure.Semin Dial.2009; 22(6):644-651
[42]李全瑞,郭增玉,陈秉良,等.维持性血液透析对尿毒症患者血脂水平影响及相关分析[J].中国血液净化,2004,3(7)：358-360
[43]Goglia F, Skulachev V P.A function for novel uncoupling proteins:antioxidant defense of mitochondrial matrix by translocating fatty acid peroxides from the inner to the outer membrane leaflet.FASEB J,2003,17:1585-1591.
[44]Ward RA, Ouseph R, McLeish KR.Effects of high-flux dialysis on oxidant stress [J].Kidney Int,2003,63:353-359
[45]Wanner C,Bahner U,Mattern R,et al.Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients[J].Nephrol Dial Transplant,2004,19:2570-2575
[46]Valeria Bordoni, Marta Piroddi, Francesco Galli, et al. Oxidant and Carbonyl Stress-related Apoptosis in End-Stage Kidney Disease [J]:Impact of Membrane Flux. Blood Purification,2006,24:149-156
[47]孟建中,宋平,李丹丹,等.晚期蛋白质氧化产物(AOPP)对血液透析患者单核细胞趋化因子受体CXCR2的影响[J].中国血液净化,2004,3(1)：30-33
[48]National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease:evaluation, classification and stratification [J]. AmJ Kidney Dis,2002, 39 Suppl 1:S1-S266
[49]Jonathan H, Peter ST. Alp I, et al. The elephant in uremia Oxidant stress as a unifying concept of cardiovascular disease inuremia[J]. Kidney Int,2002,62: 1524-1538.
[50]冯曦,刘同强,李娟娟.N—乙酰半胱氮酸对糖尿病大鼠肾脏氧化应激的影响[J].中国临床医学,2008,15(6)：842-843.
[51]Wanner C,Bahner U,Mattern R,et al.Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients[J].Nephrol Dial Transplant,2004,19:2570-2575
[52]Chen YH,Shi W,Liang XL, et al.Effect of blood sample type on the measurement of advanced oxidation protein products as a biomarker of inflammation and oxidative stress in hemodialysis patients[J].Biomarkers,2011,16(2):129-135
[1]Delbosc S, Paizanis E, Magous R, et al. Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat [J]. Atherosclerosis,2005,179(1):43-49.
[2]ShinMH, Moon YJ, Seo JE, et al.Reactive oxygen species produced by NADPH oxidase,xanthine oxidase, and mitochondrial electron transport system mediate heat shock-induced MMP-1 and MMP-9 expression [J].Free Radic BiolMed, 2008,44(4):635-645.
[3]Libby P, Ganz P.Restenosis revisited-new targets, new therapies [J].N Engl J Med, 1997,337 (6):418-419
[4].Young IS, McEneny J.Lipoprotein oxidation and atherosclerosis [J].B iochem Soc Trans,2001,29(Pt 2):358-362.
[5]MadamanchiNR, RungeMS. Mitochondrial dysfunction in atherosclerosis[J]. Circ Res,2007,100(4):460-473.
[6]Descamps-Latscha B, Witko-SarsatV, Nguyen-Khoa T, et al. Advanced oxidation protein products as risk factors for atherosclerotic cardiovascular events in nondiabetic predialysis patients [J]. Am J Kidney Dis,2005,45(1):39-47.
[7]Witko-Sarsat V,Friedlander M,Capeillere-Blandin C,et al.Adanced oxidation protein products as a novel marker of oxidative stress in uremia.Kidney Int,1996;49(5):1304-1313
[8]杨小兵,侯凡凡,武强,等.慢性肾脏病患者晚期氧化蛋白产物血症及其与动脉粥样硬化的关系[J].中华内科杂志,2005,44：342-346
[9]Roucou X, Antonsson B, MartinouJC.Involvement of mitochondria in Apoptosis [J].Cardiol Clin,2001,19(1):45-55.
[10]Himmelfarb J, Stenvinkel P, Ikizler TA, et al. The elephant in uremia:oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int,2002, 62:1524-1538
[11]Ward RA, Mclesh KR. Polymorphonuclear leukocyte oxidative burst is enhanced in patients with chronic renal insufficiency.J Am Soc Nephro,1999;5:1697-1702
[12]刘晓燕,钟一红,刘红,等.慢性肾脏病患者氧化应激状态及其相关影响因素.上海医学,2009,32(9)：787-790
[13]张爱华,梁立均,朱宁,等.血液透析对维持性血透患者体内氧化应激和一氧化氮水平的影响.中国医师杂志,2004,6(12)：1631-1633
[14]Canaud B, Cristol JP, Morena M, et al. Imbalance of oxidants and antioxidants in hemodialysis patients.Blood Purif,1999; 17:99-106
[15]Deleo FR, Renee J, McCormick S, et al. Neutrophils exposed to bacterial lipopolysaccharide upregulate NADPH oxidase assembly.J Clin Invest,1998;101:455-463
[16]Koenig JS, Fischer M, Bulant E, et al. Antioxidant status in patients on chronic hemodialysis therapy:impact of parenteral selenium supplementation.Wien Klin Wochenschr,1997; 109:13—19
[17]Herrera J, Nava M, Romero F, et al. Melatonin preents oxidative stress resulting from iron and erythropoietin administration.Am J Kidney Dis,2001; 37(4):750-757
[18]Kristal B, Shurtz- Swirskz R, Shasha SM, et al. Interaction between erythropoietin and peripheral polymorphonuclear leukocytes in hemodialysis patients. Nephrol,1999,81(4):406-413
[19]李文斌,朱竹先,魏勇,等.维持性血液透析患者心血管并发症与炎症反应及氧化应激的相关性研究。南京医科大学学报,2010,30(3)409-411
[20]张莹,刘俊,陶惠琴,等.超纯水对维持性血液透析患者氧化应激和炎症水平的影响.南方医科大学学报,2007；27(9)：1435-1438
[21]刘玲,钟玲,冯利平,等.不同血液净化方式对晚期氧化蛋白产物的清除及其对动脉粥样硬化的影响.第二军医大学学报,2008,12(29)：1528-1530
[22]唐子勇,阿拉塔,朱宁,等.血液透析患者氧化应激水平及其相关因素分析.临床内科杂志,2004,21(4)：252-254
[23]丁琼,陈雷,阚明,等.抗坏血酸对维持性血液透析氧化应激及微炎症状态的影响.安徽医药,2010,14(3)：328-330
[24]彭侃夫,吴雄飞,王军霞,等.大剂量维生素C预冲透析器对血液透析患者晚期氧化蛋白产物的影响.中国血液净化,2006,6：28-29
[25]Satoh M, Yamasaki Y, Nagake Y, et al.Oxidative stress is reduced by the long-term use of vitamin E-coated dialysis filters.Kidney Int,2001,59(5):1943-1950
[26]曲晓璐,戴芹,唐咏华,等.黄芪注射液对血液透析患者氧化应激状态的影响.中国中西医结合肾病杂志.2008,1(9)：55-56
[27]张海燕,梁伟,杨铁城,等.左卡尼汀对血液透析患者营养状况及氧化应激的影响.今日药学,2010,8(20)：34-36
[28]Pignatelli P, Lenti L, Sanguigni V, et al.Camitine inhibits arachidonic acid tumover, platelet function and oxidative stress[J].Am J Physiol Heart Circ Physiol,2003,284(1):H41-H48
[29]Panichi V,Manca Rizza G,Taccola D,et al. C-reactive protein in patients on chronic hemodialysis with different techniques and different membranes. Biomedicine and Pharmacotherapy,2005,60:14-17
[30]. Linnenweber S, Lonneman G. Effects of dialyzer membrane on interleuk-1 β (L I-β) and IL-β converting enzyme in mononuclear cells. Kidney Int,2001,59:282
[31]. Valeria Bordoni, Marta Piroddi, Francesco Galli, et al. Oxidant and Carbonyl Stress-related Apoptosis in End-Stage Kidney Disease [J]:Impact of Membrane Flux. Blood Purification,2006,24:149-156
[32]. Ward RA,Ouseph R,McLeish KR.Effects of high-flux dialysis on oxidant stress[J].Kidney Int,2003,63:353-359
[2]Himmelfarb J,stenvinkel P,Ikizer TA,et al. The elephant in uremia:oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int,2002,62: 1524-1538
[3]Locatelli F, Canaud B, Eckardt K U, et al. Oxidative stress in end-stage renal diease:an emerging threat to patient outcome.Nephrol Dial Transplant,2003, 18:1272-1280
[4]Ward RA, Mclesh KR. Polymorphonuclear leukocyte oxidative burst is enhanced in patients with chronic renal insufficiency.J Am Soc Nephro,1999; 5:1697-1702
[5]Deleo FR, Renee J, McCormick S, et al. Neutrophils exposed to bacterial lipopolysaccharide upregulate NADPH oxidase assembly.J Clin Invest,1998;101:455-463
[6]Tetta C, Biasioli S, Schiavon R, et al. An overview of hemodialysis and oxidant stress.Blood Purif,1999; 17:118-126.
[7]Morena M, Cristol JP, Canaud B. Why hemodialysis patients are in a prooxidant state? What could be done to correct the pro/antioxidant imbalance.Blood Purif,2000; 18:191-199
[8]Wratten ML, Navino C, Tetta C, et al. Haemolipdialysis.Blood Purif,1999; 17:127-133.
[9]Witko-Sarsat V, Friedlander M,Capeillere-Blandin C.et al.Adanced oxidation protein products as a novel marker of oxidative stress in uremia.Kidney Int,1996;49(5):1304-1313
[10]Canaud B, Cristol JP, Morena M, et al. Imbalance of oxidants and antioxidants in hemodialysis patients.Blood Purif,1999; 17:99-106
[11]Koenig JS, Fischer M, Bulant E, et al. Antioxidant status in patients on chronic hemodialysis therapy:impact of parenteral selenium supplementation.Wien Klin Wochenschr,1997,109:13—19
[12]Drueke T, Witko-Sarsat V, Massy Z, et al. Iron therapy, Advanced oxidation protein products, and caroid artery intima-media thickness in end-stage renal disease[J]. Circulation,2002,106(17):2212-2217.
[13]Witko-Sarsat V, Gausson V, NguyenA-T, et al. AOPP-induced activation of human neutrophil and monocyte oxidation metabolism:A potential target for N-acetylcysteine treatment in dialysis patients [J]. Kidney Int,2003,64(1):82-9
[14]Kaneda H. Taguchi J, Ogasawara K, et al. Increased level of advanced oxidation protein products in patients with coronary artery disease[J]. Athemsclemsis,2002.162:221-225.
[15]张莹,刘俊,陶惠琴,等.超纯水对维持性血液透析患者氧化应激和炎症水平的影响.南方医科大学学报,2007;27(9)：1435-1438
[16]Satoh M, Yamasaki Y, Nagake Y, et al.Oxidative stress is reduced by the long-term use of vitamin E-coated dialysis filters.Kidney Int,2001,59(5):1943-1950
[17]张海燕,梁伟,杨铁城,等.左卡尼汀对血液透析患者营养状况及氧化应激的影响.今日药学,2010,8(20)：34-36
[18]Vanholder R,De Smet R,Glorieux G,et al.Review on uremic toxins:Classification,concentration,and interindividual variability[J].Kidney Int,2003,63:1934-1943
[19]Vanholder R, Meert N, Schepers E, et al.Uremic toxins:Do we know enough to explain uremia [J].Blood Purif,2008,26:77-81
[20]Canaud B, Bragg-Gresham JL,Marshall MR, et al. Mortality risk for patients receiving hemodiafiltration versus hemodialysis:European results from the DOPPS.Kidney Int,2006,69:2087-2093
[21]蔡砺,刘惠兰,吴华,等.高通量血液透析可以有效地清除微球蛋白和改善维持性血液透析患者的慢性炎症状态.中国血液净化,2010,9,(1)：25-28
[22]唐毓嫔.高通量透析对维持性血液透析患者全身状况的影响.国际移植与血液净化,2010,7(8)：41-42
[23]. Ward RA,Ouseph R,McLeish KR.Effects of high-flux dialysis on oxidant stress[J].Kidney Int,2003,63:353-359
[24]刘玲,钟玲,冯利平,等.不同血液净化方式对晚期氧化蛋白产物的清除及其对动脉粥样硬化的影响.第二军医大学学报,2008,12(29)：1528-1530
[25]Chu PL,Chiu YL,Lin JW.et al.Effects of low-and high-flux dialyzers on oxidative stress and insulin resistance[J].Blood Purif,2008,26:213-220
[26]Delbosc S, Paizanis E, Magous R, et al. Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat [J]. Atherosclerosis,2005,179 (1): 43-49.
[27]Descamps-Latscha -B, Jungers -P, Witko-Sarsat -V. Immune system dysregulation in uremia:Role of oxidative stress [J]. Blood-Purif, 2002,20(5):481-484
[28]Capeillere-Blandin C, Gausson V, Descamps-Latscha B, et al. Biochemical and spectrophotometric significance of advanced oxidized protein products [J]. Biochim Biophys Acta,2004,1689(2):91-102
[29]丁峰,朱秋毓,顾勇,等.高级氧化蛋白产物的主要成份分析[J].中华肾脏病杂志,2006,22(1)33-36
[30]Himmelfarb J, McMonagle E. Albumin is the major plasma protein target of oxidant stress in the uriemia [J]. Kidney Int,2001,60:358-363
[31]Witko-Sarsat V, Friedlander M, Nguyen-Khoa, et al. Advanced oxidation protein products as a novel mediator of inflammation and monocyte activation in chronic renal failure [J]. J Immunal,1998,161(5):2524-32
[32]Drueke T, Witko-Sarsat V, Massy Z, et al. Iron therapy, Advanced oxidation protein products, and caroid artery intima-media thickness in end-stage renal disease[J]. Circulation,2002,106(17):2212-2217.
[33]Wratten ML, Tetta C, Ursini F, et al. Oxidant stress in hemodialysis:Prevention and treatment strategies [J]. Kidney Int,2000,76; S126-32
[34]Kalousova M, Skrha J, Zima T. Advanced glycation end-products and advanced protein products in patients with diabetes mellitus[J]. Physiol Res,2002, 51(6):597-604
[35]刘永军,祝立志,欧列斌,等.维持性血液透析患者氧化应激水平及其影响因素分析.海南医学,2005,16(2)10-11.
[36]杨小兵,侯凡凡,武强等.慢性肾脏病患者晚期氧化蛋白产物血症及其与动脉粥样硬化的关系[J].中华内科杂志,2005,44(5)：342-346
[37]Kaneda H. Taguchi J, Ogasawara K, et al. Increased level of advanced oxidation protein products in patients with coronary artery disease[J]. Athemsclemsis,2002,162: 221-225.
[38]唐子勇,阿拉塔,朱宁,等.血液透析患者氧化应激水平及其相关因素分析.临床内科杂志,2004,21(4)：252-254
[39]刘晓燕,钟一红,陈利明,等.慢性肾脏病时的氧化应激评价指标研究.中国临床医学,2010,17(5)：623-626
[40]Appel GLipid abnormalities in renal disease.Kidney Int.1991; 39(1):169-183
[41]Vaziri ND.Causes of dysregulation of lipid metabolism in chronic renal failure.Semin Dial.2009; 22(6):644-651
[42]李全瑞,郭增玉,陈秉良,等.维持性血液透析对尿毒症患者血脂水平影响及相关分析[J].中国血液净化,2004,3(7)：358-360
[43]Goglia F, Skulachev V P.A function for novel uncoupling proteins:antioxidant defense of mitochondrial matrix by translocating fatty acid peroxides from the inner to the outer membrane leaflet.FASEB J,2003,17:1585-1591.
[44]Ward RA, Ouseph R, McLeish KR.Effects of high-flux dialysis on oxidant stress [J].Kidney Int,2003,63:353-359
[45]Wanner C,Bahner U,Mattern R,et al.Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients[J].Nephrol Dial Transplant,2004,19:2570-2575
[46]Valeria Bordoni, Marta Piroddi, Francesco Galli, et al. Oxidant and Carbonyl Stress-related Apoptosis in End-Stage Kidney Disease [J]:Impact of Membrane Flux. Blood Purification,2006,24:149-156
[47]孟建中,宋平,李丹丹,等.晚期蛋白质氧化产物(AOPP)对血液透析患者单核细胞趋化因子受体CXCR2的影响[J].中国血液净化,2004,3(1)：30-33
[48]National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease:evaluation, classification and stratification [J]. AmJ Kidney Dis,2002, 39 Suppl 1:S1-S266
[49]Jonathan H, Peter ST. Alp I, et al. The elephant in uremia Oxidant stress as a unifying concept of cardiovascular disease inuremia[J]. Kidney Int,2002,62: 1524-1538.
[50]冯曦,刘同强,李娟娟.N—乙酰半胱氮酸对糖尿病大鼠肾脏氧化应激的影响[J].中国临床医学,2008,15(6)：842-843.
[51]Wanner C,Bahner U,Mattern R,et al.Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients[J].Nephrol Dial Transplant,2004,19:2570-2575
[52]Chen YH,Shi W,Liang XL, et al.Effect of blood sample type on the measurement of advanced oxidation protein products as a biomarker of inflammation and oxidative stress in hemodialysis patients[J].Biomarkers,2011,16(2):129-135
[1]Delbosc S, Paizanis E, Magous R, et al. Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat [J]. Atherosclerosis,2005,179(1):43-49.
[2]ShinMH, Moon YJ, Seo JE, et al.Reactive oxygen species produced by NADPH oxidase,xanthine oxidase, and mitochondrial electron transport system mediate heat shock-induced MMP-1 and MMP-9 expression [J].Free Radic BiolMed, 2008,44(4):635-645.
[3]Libby P, Ganz P.Restenosis revisited-new targets, new therapies [J].N Engl J Med, 1997,337 (6):418-419
[4].Young IS, McEneny J.Lipoprotein oxidation and atherosclerosis [J].B iochem Soc Trans,2001,29(Pt 2):358-362.
[5]MadamanchiNR, RungeMS. Mitochondrial dysfunction in atherosclerosis[J]. Circ Res,2007,100(4):460-473.
[6]Descamps-Latscha B, Witko-SarsatV, Nguyen-Khoa T, et al. Advanced oxidation protein products as risk factors for atherosclerotic cardiovascular events in nondiabetic predialysis patients [J]. Am J Kidney Dis,2005,45(1):39-47.
[7]Witko-Sarsat V,Friedlander M,Capeillere-Blandin C,et al.Adanced oxidation protein products as a novel marker of oxidative stress in uremia.Kidney Int,1996;49(5):1304-1313
[8]杨小兵,侯凡凡,武强,等.慢性肾脏病患者晚期氧化蛋白产物血症及其与动脉粥样硬化的关系[J].中华内科杂志,2005,44：342-346
[9]Roucou X, Antonsson B, MartinouJC.Involvement of mitochondria in Apoptosis [J].Cardiol Clin,2001,19(1):45-55.
[10]Himmelfarb J, Stenvinkel P, Ikizler TA, et al. The elephant in uremia:oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int,2002, 62:1524-1538
[11]Ward RA, Mclesh KR. Polymorphonuclear leukocyte oxidative burst is enhanced in patients with chronic renal insufficiency.J Am Soc Nephro,1999;5:1697-1702
[12]刘晓燕,钟一红,刘红,等.慢性肾脏病患者氧化应激状态及其相关影响因素.上海医学,2009,32(9)：787-790
[13]张爱华,梁立均,朱宁,等.血液透析对维持性血透患者体内氧化应激和一氧化氮水平的影响.中国医师杂志,2004,6(12)：1631-1633
[14]Canaud B, Cristol JP, Morena M, et al. Imbalance of oxidants and antioxidants in hemodialysis patients.Blood Purif,1999; 17:99-106
[15]Deleo FR, Renee J, McCormick S, et al. Neutrophils exposed to bacterial lipopolysaccharide upregulate NADPH oxidase assembly.J Clin Invest,1998;101:455-463
[16]Koenig JS, Fischer M, Bulant E, et al. Antioxidant status in patients on chronic hemodialysis therapy:impact of parenteral selenium supplementation.Wien Klin Wochenschr,1997; 109:13—19
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