重组人促红素对老年慢性肾衰病人氧自由基及抗氧化酶活性的 …

目的 探讨重组人促红素（ｒＨ－ＥＰＯ）对慢性肾衰患者体内氧自由基及抗氧化酶活性的影响。方法 测定１９例老年慢性肾衰尿毒症期患者ｒＨ－ＥＰＯ治疗前后血浆ＭＤＡ、ＳＯＤ及红细胞ＧＳＨ－Ｐｘ含量。结果 ｒＨ－ＥＰＯ治疗后慢性肾衰病人ＭＤＡ含量降低，ＳＯＤ、ＧＳＨ－Ｐｘ活性升高。结论 ｒＨ－ＥＰＯ纠正肾性贫血同时，可清除体内氧自由基，提高抗氧化酶活性。     

重组人促红素对老年肾衰患者免疫功能及营养状况的影响

老年慢性肾衰竭(CRF)患者常有多系统、多器官疾病的并存,治疗上更为棘手.重组人促红素( r-HuEPO)作为促进红细胞生成的药物已广泛应用于临床肾性贫血等疾病的治疗[1,2],近来,笔者应用r-HuEPO治疗老年CRF患者,观察其对免疫功能和营养状况的影响.1 资料与方法1.1 一般资料 2009年3月至2011年3月我科收治的48例老年CRF患者,诊断参照慢性肾衰竭的诊断标准.其中男31例,女17例,年龄61～85岁;原发病中慢性肾小球肾炎18例,高血压12例,糖尿病11例,慢性肾盂肾炎4例,原因不明3例;CRF临床分期:肾功能不全失代偿期35例(血肌酐178～445 μmol/L),尿毒症期13例(＞445 μmol/L).     

慢性支气管炎患者红细胞中抗氧化酶活性的分析

检测了慢性支气管炎(20例)和正常人(20例)红细胞中的谷胱甘肽过氧化物酶(GSH—P_x)、谷胱甘肽转硫酶(GST),超氧化物歧化酶(SOD),过氧化氢酶(Cat)及血浆中的丙二醛(MDA)。结果显示慢性支气管炎患者的GSH—P_x·SOD活性明显降低,MDA含量明显增加,提示自由基的损伤作用增强,这在肺气肿的形成过程中具有重要意义。     

补肾活血颗粒联合重组人促红素治疗慢性肾脏病肾性贫血的疗效

目的 探究补肾活血颗粒联合重组人促红素治疗慢性肾脏病(CKD)肾性贫血疗效及对血清铁参数和炎症因子水平的影响。方法 104例CKD肾性贫血患者按随机信封法分为治疗组和对照组各52例,对照组予以重组人促红素皮下注射,治疗组予以补肾活血颗粒剂冲服联合重组人促红素皮下注射,均治疗8 w。比较两组治疗前后中医症状积分、贫血指标[血红蛋白(Hb)、红细胞计数(RBC)、红细胞比容(Hct)]、血清铁参数[血清铁(Fe)、转铁蛋白(TRF)、转铁蛋白饱和度(TSAT)、铁调素(Hepc)]及炎症因子[白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、低氧诱导因子(HIF)-1α],评价疗效及安全性。结果 治疗后2、4、8 w,治疗组中医症状积分显著低于对照组(P<0.05)。治疗后8 w,两组Hb、RBC、Hct显著高于治疗前,且治疗组显著高于对照组(P<0.05)。治疗后8 w,两组血清Fe、TSAT显著高于治疗前,Hepc显著低于治疗前,且治疗组TSAT显著高于对照组,Hepc显著低于对照组(P<0.05)。治疗后8 w,两组血清IL-6、TNF-α、HIF-1α显著低于治...     

胞二磷胆碱联合重组人促红素治疗新生儿缺氧缺血性脑病的临床疗效及其对患儿神经功能的影响

背景 新生儿缺氧缺血性脑病(HIE)具有较高的病死率、致残率,临床主要采用胞二磷胆碱治疗新生儿HIE并取得了一定疗效,但该药物不良反应较多,一定程度上影响了临床疗效,因此探寻新的治疗方式对提高新生儿HIE的治疗效果具有重要的临床意义.目的 探讨胞二磷胆碱联合重组人促红素治疗新生儿HIE的临床疗效及其对患儿神经功能的影响...     

甲状腺功能减退大鼠心肌抗氧化能力及ATP酶活性的实验研究

目的 研究甲状腺功能减退大鼠心肌抗氧化能力及心肌膜标志酶活性的变化，探讨甲状腺功能减退致心肌损伤的发病机制。方法 30只Wistar大鼠随机分为对照组和甲状腺功能减退组，用低碘饲料和不含碘的水喂养大鼠复制甲状腺功能减退动物模型。制备心肌组织匀浆，提取心肌生物膜，测定心肌组织丙二醛（MDA）水平、谷胱甘肽过氧化物酶（GSH—Px）和超氧化物歧化酶（SOD）活性及心肌生物膜Na^＋，K^＋-ATP酶、Mg^2＋-ATP酶、Ca^2＋-ATP酶、Ca^2＋，Mg^2＋-ATP酶活性。结果 与对照组比较，甲状腺功能减退组血清T3、T4均明显下降（P〈0．05或〈0．01）：心肌组织MDA水平和GSH—Px活性明显升高（P〈0．05），而SOD活性明显降低（P〈0．05）；心肌生物膜Na^＋，K^＋-ATP酶、Ca^2＋-ATP酶、Mg^2＋-ATP酶、Ca^2＋，Mg^2＋-ATP酶活性明显下降（P〈0．05）。结论 甲状腺功能减退时心肌抗氧化能力下降，心肌过氧化损伤，表现为心肌膜上参与代谢的ATP酶活性降低。     

利舒康胶囊对高原地区中老年人氧自由基代谢指标的影响

长期生活在低氧环境中的高原居民其机体防御能力下降，致使脂质代谢产物增多而对机体产生长期的持续性损害，可造成高原人早老、早衰及慢性高原病的发生与发展。利舒康胶囊是新研制的抗缺氧和治疗高原病的药物，本文就利舒康胶囊对高原地区中老年人体内氧自由基代谢指标的影响进行探讨。     

乙肝Ⅱ号对小鼠免疫性慢性肝损伤抗氧化功能的影响

目的：研究乙肝Ⅱ号对免疫性肝损伤小鼠抗氧化功能的影响及其机理。方法：取异种动物的肝提取物作为抗原,免疫纯系小鼠,产生抗肝抗体,形成慢性实验性免疫性肝损伤,观察小鼠肝匀浆丙二醛（MDA）含量,超氧化物歧化酶（SOD）及谷胱甘肽过氧化物酶（GSH－Px)活力的变化以及乙肝Ⅱ号对MDA、SOD和GSH－Px变化的影响。结果：乙肝Ⅱ号组与模型组相比,肝均浆MDA含量下降,SOD活性国逄,GSH－Px活力上升,变化的程度与用药量呈量效关系,且抗氧化作用优于阳性对照药物乙肝宁冲剂,结论：乙肝Ⅱ号对免疫性肝损伤小鼠具有抗氧化功能损伤的作用。     

急性心肌梗死患者氧化损伤及抗氧化酶活性

为了评价急性心肌梗死患者氧化损伤程度及与抗氧化酶活性的关系。采用鲁米诺依赖的中性粒细胞化学发光法 ,对 6 0例急性心肌梗死患者及 6 2例年龄和性别匹配的健康对照者 ,检测外周血中性粒细胞产生氧自由基的水平 ;采用化学定量法测定血脂质过氧化终末产物———丙二醛的浓度及超氧化物歧化酶、谷胱甘肽过氧化物酶、肌酸磷酸激酶的活性。结果发现 ,急性心肌梗死组中性粒细胞化学发光峰值、积分、吞噬指数、血浆丙二醛浓度较对照组明显升高 (P均 <0 .0 0 1) ;血浆超氧化物歧化酶和谷胱甘肽过氧化物酶活性较对照组均明显降低 (P均 <0 .0 0 1) ;中性粒细胞化学发光峰值与血浆丙二醛浓度及血清肌酸磷酸激酶活性存在明显的正相关 ,前者r=0 .5 8(F =148.9,P <0 .0 1,n =12 2 ) ,相关方程为Y =- 482 4.9+144 1.2X ;后者r=0 .47(F =6 8.9,P <0 .0 1,n =12 2 ) ) ,相关方程为Y =1190 .8+0 .730 4X。中性粒细胞化学发光峰值与血浆超氧化物歧化酶活性呈显著的负相关 ,其相关系数为r=- 0 .6 3 (F =193 .2 ,P <0 .0 1,n =12 2 ) ,相关方程为Y =82 30 .0 - 78.1X ,。此结果提示 ,急性心肌梗死患者体内存在着明显的氧化损伤 ,同时也导致体内抗氧化能力减弱 ,氧化损伤的程度可能与心肌梗死的范围有关。     

氧自由基在COPD患者中的变化及临床意义

目的探究氧自由基在COPD患者中的变化及临床意义。方法选取我院收治的COPD患者120例纳入观察组,并选取同期120例健康体检者作为对照组进行血液氧自由基检测。结果观察组氧化物歧化酶(SOD)、谷胱甘肽氧化酶(GSH-PX)指标均明显低于对照组,而脂质过氧化物(LPO)含量高于对照组,两组对比存在统计学差异;结论测定上述氧自由基指标对疾病的确诊、判定病情及指导临床治疗具有重要意义。     

重组人红细胞生成素对维持性血液透析的慢性肾功能衰竭患者血清瘦素水平的影响

目的　探讨重组人红细胞生成素 (rHuEPO)对维持性血液透析 (HD)的慢性肾功能衰竭 (CRF)患者血清瘦素水平的影响及其意义。方法　 80例行HD的CRF患者分为不用rHuEPO治疗组和使用rHuEPO治疗组 ;使用rHuEPO治疗的又分三组 (3个月组 ,6个月组 ,12个月组 )。采用ELISA法测定血清瘦素水平 ,放免法测定血清TNF α水平。结果　使用rHuEPO治疗 6个月后 ,血清瘦素水平明显低于治疗前及未用rHuEPO治疗组 (P <0 .0 5 ) ;血清TNF α、CRP水平也明显低于治疗前及未用rHuEPO治疗组 (P <0 .0 5 )。结论　使用rHuEPO治疗 6个月后血清瘦素水平明显下降     

乌司他丁与川芎嗪合用对急性胰腺炎大鼠氧自由基影响的研究

目的探讨乌司他丁、川芎嗪两药合用对急性胰腺炎（AP）大鼠氧自由基的影响。方法SD大鼠75只,随机分为5组,每组15只。通过胰胆管逆行性注射牛磺胆酸钠制成AP大鼠模型。分别观察各实验组血清SOD、MDA的变化。结果①AP组与假手术组相比,血清SOD水平明显降低（P〈0.05）,血清MDA水平明显升高（P〈0.05）。②乌司他丁治疗组、川芎嗪治疗组及乌司他丁、川芎嗪合用组与AP组相比,血清SOD水平明显升高（P〈0.05）,血清MDA水平明显降低（P〈0.05）。③乌司他丁、川芎嗪合用组与乌司他丁治疗组、川芎嗪治疗组相比,血清SOD水平明显升高（P〈0.05）,血清MDA水平明显降低（P〈0.05）。结论乌司他丁、川芎嗪通过升高SOD保护性因子、降低MDA损伤性因子,对AP有治疗作用,而乌司他丁、川芎嗪合用效果更显著。     

Pharmacokinetics of intravenous recombinant human erythropoietin in patients with chronic renal failure

In order to improve our understanding of the dose-concentration and concentration-effect relationships, the pharmacokinetics of recombinant erythropoietin were studied after the initial dose (n = 6) and after repeated doses (n = 9) administered intravenously in patients with chronic renal failure. Several venous blood samples were collected before (to obtain the baseline concentration) and after an intravenous dose of erythropoietin. A radioimmunoassay was used to determine the erythropoietin concentration in the samples. The apparent volume of distribution at steady state was 4.2 +/- 0.91 (initial dose) and 3.7 +/- 0.61 (repeated dosing), which is close to the assumed plasma volume in these patients. The half-life was 5.3 +/- 1.3 h and 5.8 +/- 1.2 h in the two groups, respectively, and is therefore too short for any accumulation to be expected when dosing three times per week. Consequently, no difference in baseline values could be detected between the groups. The clearance of erythropoietin in the groups was estimated to be 11.4 +/- 7.0 ml min-1 and 7.8 +/- 3.8 ml min-1, respectively. Erythropoietin kinetics did not differ after repeated dosing compared to the single initial dose. Intravenous administration of erythropoietin will result in high peak concentrations followed by a rapid decline to basal values.     

Inhibitors of recombinant human erythropoietin in chronic renal failure.

This study investigates which factors influence the response of administered recombinant human erythropoietin (Re-HuEPO) with respect to the increase of haemoglobin in patients with end-stage renal disease. Pharmacokinetic parameters of administered Re-HuEPO in patients with end-stage renal disease and considerable differences in the amount of Re-HuEPO required ("Re-HuEPO-need") to obtain an increase of haemoglobin, revealed a pattern of dose-dependent first-order elimination without significant interindividual differences between the patients. As variable immunological inhibitors of erythropoietin are also absent, the administered Re-HuEPO seems to be equally available to the erythron in the various patients. In vitro incubation experiments with bone marrow cells show that the sera from patients with end-stage renal disease contain inhibitors of the erythropoietin-induced stimulation of bone marrow cells. As the patients' sera differ with regard to the degree of inhibition of erythropoietin bioactivity, this inhibition may also be responsible for the interindividual differences in amount of erythropoietin required. Besides a reduced endogenous production of erythropoietin, these inhibitors of the bioactivity of erythropoietin may also contribute to the pathogenesis of anaemia in patients with chronic renal failure.     

Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin

PURPOSE: The purpose of this study was to determine the efficacy of recombinant human erythropoietin (rHuEPO) given subcutaneously three times/week in patients with chronic renal failure and anemia (predialysis). PATIENTS AND METHODS: Eleven patients with predialysis chronic renal failure participated in a double-blind, placebo-controlled study of subcutaneously administered erythropoietin. For 12 weeks, patients received either rHuEPO 100 mu/kg body weight three times/week subcutananeously or a placebo. After 12 weeks of placebo, patients now also received rHuEPO in a dose up to 150 mu/kg three times/week until target hematocrit was achieved. Throughout the study, blood pressure was monitored closely and blood work was obtained regularly for hemoglobin, hematocrit, reticulocyte count, and iron profile determinations. RESULTS: At 12 weeks, the hematocrit of the treated group had risen from 29% +/- 2% to 35% +/- 2% (p less than 0.001). The placebo group baseline hematocrit was 28% +/- 2% and at 12 weeks 26% +/- 2% After 12 weeks of rHuEPO therapy, the hematocrit of the prior placebo group was 32% +/- 2% (p less than 0.001 versus baseline). No significant change in biochemical parameters was noted. Mean blood pressure values were comparable before and after treatment. All protein ultimately required iron supplementation. In two patients, the rate of progression of renal failure appeared to increase as their hematocrit rose and rHuEPO was discontinued. CONCLUSIONS: It is concluded that rHuEPO given subcutaneously is an effective and safe therapy for patients with chronic renal failure who are anemic and who are not receiving dialysis.     

肝硬化患者红细胞免疫功能与脂质过氧化关系的研究

探讨肝硬化患者红细胞免疫功能的变化及其与脂质过氧化的关系。应用红细胞酵母菌花环法测定红细胞免疫功能 ,并采用化学比色法测定血浆丙二醛 (MDA)、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH -Px)含量。其中肝硬化患者 31例 ,健康对照 30例。肝硬化组RBC -IC花环率明显提高 ,P <0 .0 5 ;而RBC -C3b受体花环率与正常人无显著性差异 (P >0 .0 5 )。肝硬化组SOD、GSH -Px、SOD/MDA低于正常 (P <0 .0 1) ;而MDA明显高于正常 (P <0 .0 1)。线性相关分析显示 ,RBC -C3b花环率与MDA呈显著负相关 (r= 0 .42 3,P <0 .0 5 )。RBC -ICR与MDA明显正相关 (r=0 .5 2 3,P <0 .0 5 )。肝硬化患者红细胞免疫粘附功能降低 ,与活性氧代谢紊乱密切相关     

重组促红细胞生成素对慢性肾衰竭患者左心室重量和结构的影响

目的　观察用重组促红细胞生成素 (rHuEPO)改善贫血后对慢性肾衰竭患者左室重量和结构的影响。方法　将 2 4例慢性肾衰竭患者分为透析前组 (Ⅰ组 )和维持血透组 (Ⅱ组 ) ,在rHuEPO治疗前及治疗 4月后行血红蛋白 (Hb)测定和心脏超声检查。结果　rHuEPO治疗后Hb显著升高 (Ⅰ组 68g/L± 10 g/Lvs 10 1g/L± 11g/L ,Ⅱ组 67g/L± 6g/Lvs 94g/L± 8g/L ,P <0 .0 5 ) ;左室重量指数 (LVMI)显著下降 (Ⅰ组 185 .6± 44 .6vs 15 8.3± 44 .1,Ⅱ组 15 8.0± 2 6.9vs13 1.6± 2 2 .1,P <0 .0 5 ) ;两组左室收缩期末内径 (LVESD)及舒张期末内径 (LVEDD )均较治疗前显著下降 (P <0 .0 5 )。相关分析显示 ,Hb与左室重量和结构相关 ,贫血参与了左室肥厚 (LVH )的发生。结论　rHuEPO可引起LVMI下降 ,rHuEPO纠正贫血 ,有利于左室重量及结构异常的好转     

Pure red-cell aplasia caused by the antibody to recombinant erythropoietin, epoetin-beta, in a Japanese patient with chronic renal failure

A 68-year-old male with chronic renal failure and anemia received recombinant human erythropoietin (rHuEPO), epoetin beta, for approximately 1 year. Although the agent was initially effective for improving anemia, anemia refractory to EPO administration appeared and then worsened later, and pure red-cell aplasia (PRCA) was diagnosed. Anti-EPO antibody was detected by radioimmunoprecipitation (RIP) assay in the patient's serum. The antibody inhibited the proliferation of EPO-dependent cell line in a dose-dependent manner neutralizing EPO activity. The antibody also reacted with the other epoetin alfa products. The antibody did not recognize the carbohydrate moieties or denatured epoetin beta. The result suggested that the antibody recognized the conformational epitope of epoetin beta peptide molecule. Withdrawal of EPO and administration of cyclosporine decreased the titers of antibody; however, erythroid progenitor has not yet regenerated although the requirement for red blood cell transfusion is decreasing.     

犬心肺复苏后心肌细胞凋亡和氧自由基的变化

目的观察犬心跳骤停复苏后心肌细胞凋亡和氧自由基的变化。方法12只犬随机分为2组,心肺复苏组(cardiopulmo nary resascitation,CPR组)和空白对照组,每组6只,CPR组电击诱发犬心室颤动,3分钟后开始复苏,采用Swan-Ganz漂浮导管监测复苏前和恢复自主循环后0,0.5,1,2,4,6小时的平均动脉压、心输出量和肺动脉楔压,6小时后取心肌组织,TUNEL法检测心肌细胞凋亡,心肌组织匀浆测丙二醛和超氧化物歧化酶的活性。结果两组各血流动力学指标在心跳骤停前无统计学差异,CPR组的平均动脉压在恢复自主循环4小时和6小时低于空白对照组。CPR组的肺动脉楔压从心跳骤停前的(5.0±1.3)mmHg持续上升,到复苏后6小时达到(28.8±4.8)mmHg,各观察点均高于空白对照组,心输出量在复苏成功后随时间延长而下降,6小时降至最低,复苏后各观察点均低于空白对照组。CPR组心肌细胞凋亡明显多于空白对照组。复苏后6小时,CPR组心肌组织丙二醛活性高于空白对照组,而超氧化物歧化酶活性低于空白对照组。结论电击诱发心室颤动犬复苏成功后存在着心功能不全,其可能与复苏后心肌氧自由基的产生和心肌细胞凋亡增加,以及内源性抗氧化机制的削弱有关。     

维生素E对D-半乳糖亚急性中毒拟衰老模型鼠氧自由基及相关生化指标的影响

目的研究维生素E(VE)对D-半乳糖(D-gal)亚急性中毒拟衰老模型鼠自由基产生及相关生化指标的影响。方法昆明小鼠颈背部皮下注射D-gal40mg·kg-1.d-1制备D-gal亚急性中毒导致的衰老鼠模型。将模型鼠分为模型组和高、中、低剂量VE组(分别灌胃60、30、15mg·kg-1.d-1VE),10w后杀鼠。采用硫代巴比妥酸(TBA)法检测血清中丙二醛(MDA)含量,黄嘌呤氧化酶法检测血清中总超氧化物歧化酶(SOD)活性;采用ISP半自动生化分析仪检测血清中血糖(Glu)、总胆固醇(TC)、甘油三酯(TG)的含量。结果模型鼠血清中MDA含量、Glu、TC、TG含量显著高于正常对照组,SOD含量显著低于正常对照组(均P<0.05),高、中、低剂量VE组血清MDA含量显著低于模型对照组,总SOD含量显著高于模型对照组(均P<0.05)。高、中、低剂量VE组小鼠血清Glu、TC、TG含量与模型对照组无显著差异。结论VE可以对衰老鼠的氧自由基损伤发挥保护作用,为临床将VE作为一种抗衰老药物应用提供了进一步的试验依据。