【作者】 李春红；

【导师】 夏天；

【作者基本信息】 天津医科大学 ， 内科学， 2011， 硕士

【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-12.0373.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。更多还原

【Abstract】 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.更多还原