静脉补铁联合维生素E对血液透析患者贫血的疗效及氧化应激的影响

目的 探讨抗氧化剂维生素E(VitE)联合静脉用蔗糖铁治疗维持性血液透析患者肾性贫血的疗效及对氧化应激的影响.方法 选择维持性血液透析(MHD)并发肾性贫血患者190例,随机分为A组99例(促红细胞生成素+静脉补铁+口服维生素E)和B组91例(促红细胞生成素+口服补铁),A组静脉用蔗糖铁(前8 w 2次/w;以后1次/w,每次100 mg),同时口服维生素E 200 mg,2次/d,总疗程12 w;B组口服多糖铁复合物胶囊150 mg,1次/d,总疗程12 w,两组患者均同时使用促红细胞生成素,剂量6 000～9 000 IU/w,皮下注射,检测两组患者治疗前后的贫血相关指标,氧化应激指标.结果 治疗12 w后,两组患者血红蛋白(Hb)、红细胞压积(Hct)都有明显升高,但B组相对较慢,两组比较差异有统计学意义,而Ret两组治疗前后差异无统计学意义;血清铁蛋白(SF)两组患者均较治疗前有明显升高,A组更加显著,两组差异有统计学意义(P＜0.05);血浆同型半胱氨酸(HCY)两组治疗前后差异均有统计学意义,A组较B组明显降低,两组治疗前后差异有统计学意义(P＜0.05).结论 静脉使用蔗糖铁同时口服维生素E可有效地纠正MHD患者铁缺乏,能有效改善贫血,且安全性较好,同时可以改善MHD患者因静脉补铁所诱导的氧化应激.     

微炎症及氧化应激对慢性肾脏病患者肾功能的影响

目的：研究非透析不同分期慢性肾脏病（chronickidneydisease,CKD）患者血清中微炎症及氧化应激相关指标的变化及对肾功能的影响。方法：对CKD第1～5期92例患者测定血清超敏C反应蛋白（hs—CRP）、脂蛋白a[LP（a）]、超氧化物歧化酶（SOD）水平,并比较它们在不同分期患者中的水平。结果：随cKD分期的增加,患者血清hs—CRP、LP（a）水平逐渐升高,血清s0D活性逐渐下降;血清hs—CRP、LP（a）水平与s0D水平呈负相关,血清s0D活性与肾小球滤过率（estimatedglomeru1arfiltrationrate,eGFR）呈正相关。结论：CKD患者均存在一定程度的微炎症、氧化应激增强,而且随着肾功能损害加重,其微炎症及氧化应激状态增强。CKD非透析患者微炎症与氧化应激反应相互促进,均参与并促进肾功能的减退。     

联合应用维生素E和维生素C对睡眠剥夺后大鼠心肌氧化应激指标的影响

目的观察联合应用维生素E(VE)和维生素C(VC)对睡眠剥夺后大鼠心肌损伤的保护作用,探讨其作用机制。方法将大鼠随机分8组,每组10只。采用改良多平台睡眠剥夺法(MMPM)建立睡眠剥夺模型,联合VE、VC灌胃给药(VE 500 mg/kg;VC 1.5 g/kg)。观察联合VE、VC对睡眠剥夺后心肌组织丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性的影响。结果与大平台组比较,睡眠剥夺后心肌细胞中MDA的含量明显增加,SOD活性有明显下降趋势;与睡眠剥夺组比较,联合VE、VC组心肌细胞中SOD活性显著提高,细胞中MDA的含量明显降低。提示联合使用VE、VC干预后,可明显降低睡眠剥夺后心肌组织氧化应激反应。结论 联合使用VE、VC可明显降低睡眠剥夺后大鼠心肌氧化应激损伤。     

静脉铁剂不同给药方式对慢性肾衰竭大鼠氧化应激的影响

目的:评价静脉铁剂总剂量给药和小剂量多次给药2种不同用药策略对慢性肾衰竭大鼠氧化应激的影响.方法:5/6肾大部切除术建立CRF大鼠模型.SD大鼠右肾切除术后第4周,将符合条件的CRF大鼠随机分为3组:静脉铁剂总剂量给药组(科莫非100 mgkg-1一次性尾静脉注射,n=6)、静脉铁剂小剂量多次给药组(科莫非10 mgkg-1,每周周一、周四尾静脉注射2次,共5周10次,n=6)、CRF组(对照组)(给予同等体积的0.9%氯化钠液尾静脉注,n=6),假手术组(Sham组,n=4)作为正常对照组.观察6周,比较各组大鼠氧化应激等差异.结果:(1) 各组CRF大鼠肾脏切除比例、基线血清肌酐和尿素氮、尾动脉收缩压、尿蛋白/肌酐比值、血红蛋白、红细胞压积及体重均无显著差异.观察6周后,CRF组大鼠的尾动脉收缩压、血清肌酐和尿素氮、尿蛋白/肌酐比值无统计学差异 (P>0.05),铁剂总剂量给药组和小剂量多次给药组大鼠血红蛋白、红细胞压积显著高于CRF对照组,静脉铁剂组之间无显著差异;(2) 血浆AOPP水平,CRF组显著高于Sham组,静脉铁剂组显著高于CRF对照组(P<0.05),小剂量多次给药组显著高于总剂量给药组;(3) 3组CRF大鼠血浆MDA均显著高于Sham组(P<0.01),静脉铁剂小剂量多次给药组显著高于总剂量给药组及CRF对照组(P<0.01),总剂量给药组与CRF对照组之间无显著差异(P>0.05);(4) 铁剂治疗组以及CRF对照组大鼠血清SOD、CAT及TAOC水平均较Sham组升高(P<0.05),铁剂治疗组血清SOD及TAOC水平与CRF对照组之间无显著差异(P>0.05),血清CAT水平较CRF对照组升高,总剂量给药组和小剂量多次给药组之间血清SOD、CAT及TAOC水平无统计学差异(P>0.05).CRF组大鼠血浆GSH-Px水平较假手术组大鼠降低(P<0.05),铁剂治疗组与CRF对照组之间无统计学差异(P>0.05).结论:静脉铁剂可以加重慢肾衰大鼠氧化应激紊乱状态,静脉铁剂单次总剂量给药方式对慢肾衰大鼠脂合氧化和蛋白氧化指标的不利影响小于小剂量多次给药方式.     

慢性肾脏病时的氧化应激评价指标研究

目的：研究慢性肾脏病（CKD）时氧化应激的评价指标,以确定可以稳定反映氧化应激水平的指标。方法：选择2008年7月—12月在复旦大学附属中山医院诊断为CKD1~5期的住院患者73例,以10例同期在骨科住院行择期手术的无肾脏疾病患者为对照组,测定其血浆晚期氧化蛋白产物（AOPP）、丙二醛（MDA）以及谷胱甘肽过氧化物酶（GSH-PX）、过氧化物歧化酶（SOD）和过氧化氢（CAT）的活力。结果：血浆AOPP和MDA水平CKD组显著高于对照组（P〈0.05）,其中血浆AOPP水平随着肾功能减退逐渐升高,在CKD1~5期各组之间均有显著差异（P〈0.05）。血浆GSH-PX、SOD和CAT水平CKD组显著低于对照组（P〈0.05）,其中前两者在CKD患者随着肾功能减退呈逐渐降低的趋势（P〈0.05）。结论：CKD患者存在过度氧化应激。血浆AOPP水平随着肾功能的减退逐渐升高,它是反映机体氧化应激水平的的稳定指标,并可较好地区别CKD不同肾损伤阶段氧化应激反应的变化;GSH-PX和SOD是较好的抗氧化指标。     

维生素E联合黄芪注射液对维持性血液透析患者氧化应激的干预效果

目的:探讨维生素E联合黄芪注射液对维持性血液透析患者氧化应激状态的干预效果以及使用安全性。方法:将75例维持性血液透析治疗患者分为维生素E治疗组(A组)、维生素E联合黄芪注射液治疗组(B组)和常规血液透析治疗组(C组)各25例,观察各组患者治疗前后过氧化物歧化酶(SOD)、血清丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、循环晚期氧化蛋白产物(AOPP)的变化及白蛋白(Alb)、血红蛋白(Hb)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)的水平。结果:A组与B组治疗后SOD、MDA、GSH-Px、AOPP较治疗前均有显著改善(P0.05);治疗后,A组与B组血清MDA、AOPP水平较C组低(P0.05),A组与B组血清SOD、GSH-Px水平较C组高(P0.05),并且B组各应激指标的改善程度较A组更为显著(P0.05)。在治疗期间,无血栓、出血等并发症的发生。结论:维生素E联合黄芪注射液可以显著改善维持性血液透析患者氧化应激状态,并且短期应用无副作用。     

维生素E减轻糖尿病大鼠造影剂肾损害氧化应激的实验研究

目的:探讨维生素E对糖尿病大鼠造影剂肾损害的保护作用及其作用机制。方法:将实验动物分为正常组(N),糖尿病组(DM),造影剂组(CM)和治疗组(T)。检测造影后各组血肌酐(Scr),内生肌酐清除率(Ccr),尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG),并检测肾组织超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性、丙二醛(MDA)含量、诱导型一氧化氮合酶(iNOS)活性。同时留取肾脏作PAS染色并作病理形态学分析。结果:与CM组相比,T组Scr下降(P<0.01),Ccr明显上升(P<0.01),尿NAG下降(P<0.01),而肾脏抗氧化酶活性,包括总超氧化物歧化酶(T-SOD)、CAT明显上升(P<0.05),MDA含量下降(P<0.01),iNOS活性明显下降(P<0.01)。病理形态学发现T组肾组织损害特别是肾小管变性坏死较CM组减轻。结论:维生素E能减轻糖尿病造影剂肾损害,其作用与其减轻糖尿病造影剂肾损害中NO参与的氧化应激反应有关。     

维持性血液透析尿毒症患者静脉补铁与氧化应激

铁缺乏在慢性肾脏病患者中常见,特别是在维持性血液透析(maintenance haemodialysis,MHD)尿毒症患者中。其原因包括：频繁取血化验、透析时血液残留于体外循环管路、慢性胃肠道失血以及摄人不足等,均可造成血液丢失(铁的丢失);使用促红细胞生成素(EPO)治疗增加了红细胞的生成率,也增加了对铁的需求。当上述两种情况合并存在时,血液透析患者要保持充分的铁储备非常困难。     

维生素D检测与慢性肾脏病研究进展

维生素D(VitD)是一组亲脂性甾体类固醇衍生物的统称,其亚组分很多,但与人体健康相关的主要是VitD 2和VitD 3,其中VitD 2主要来源于植物性膳食,而VitD 3主要通过光照经皮肤合成,少数来源于动物性膳食[1]。最近研究发现,VitD除了与骨骼疾病[2-4]、血脂紊乱[5]和自身免疫性疾病[6]等有关外,还发现其缺乏或不足与慢性肾脏病(CKD)的发生和发展密切相关[7]。CKD是临床上多见的一种慢性疾病,因其发病率较高而知晓率较低,已成为全球一大公共卫生问题。越来越多的研究发现,VitD缺乏或不足可能与CKD发病、病情严重程度及预后有关,特别是在晚期CKD患者和肾移植患者中,对VitD的依赖表现更加明显[8-10]。本文就VitD缺乏与CKD的关系综述如下。     

静脉补铁对慢性肾衰竭大鼠氧化应激状态的影响

[目的]研究静脉补铁对慢性肾衰竭大鼠氧化应激状态的影响，为慢性肾衰竭铁剂治疗方法的选择及静脉补铁时营养干预改善机体氧化应激状态提供实验依据。[方法]随机将32只大鼠分为正常对照组、正常补铁组、肾衰竭对照组、肾衰竭补铁组。。肾衰竭组通过采用腺嘌呤灌胃的方法建立大鼠肾衰竭模型，肾衰竭补铁组与正常补铁组给予一次性尾静脉注射铁剂，两周后观察各组血肌肝（Cr）、尿素氮（BUN）、血清铁、铁蛋白、血浆还原型谷胱甘肽（GSH）、维生素E、一氧化氮（No）、丙二醛（MDA）含量的变化。[结果]肾衰竭各组Cr、BUN与正常两组比较，均有统计学意义（〈0．05）；各补铁组血清铁、铁蛋白与各对照组比较，均有统计学意义（P〈0．05）；肾衰竭对照组与正常对照组血浆GSH、维生素E、NO、MDA比较，均有统计学意义（P〈0．05）；。肾衰竭补铁组与。肾衰竭对照组血浆N0、MDA比较。均有统计学意义（P〈0．05）。[结论]慢性肾衰竭大鼠体内存在氧化应激，静脉补铁可能进一步加剧其体内氧化应激状态。     

静脉补铁对慢性肾衰竭大鼠氧化应激状态的影响

[目的]研究静脉补铁对慢性肾衰竭大鼠氧化应激状态的影响,为慢性肾衰竭铁剂治疗方法的选择及静脉补铁时营养干预改善机体氧化应激状态提供实验依据.[方法]随机将32只大鼠分为正常对照组、正常补铁组、肾衰竭对照组、肾衰竭补铁组.肾衰竭组通过采用腺嘌呤灌胃的方法建立大鼠肾衰竭模型,肾衰竭补铁组与正常补铁组给予一次性尾静脉注射铁剂,两周后观察各组血肌肝(Cr)、尿素氮(BUN)、血清铁、铁蛋白、血浆还原型谷胱甘肽(GSH)、维生素E、一氧化氮(NO)、丙二醛(MDA)含量的变化.[结果]肾衰竭各组Cr、BUN与正常两组比较,均有统计学意义(＜0.05);各补铁组血清铁、铁蛋白与各对照组比较,均有统计学意义(P＜0.05);肾衰竭对照组与正常对照组血浆GSH、维生素E、NO、MDA比较,均有统计学意义(P＜0.05);肾衰竭补铁组与肾衰竭对照组血浆NO、MDA比较,均有统计学意义(P＜0.05).[结论]慢性肾衰竭大鼠体内存在氧化应激,静脉补铁可能进一步加剧其体内氧化应激状态.     

静脉注射丙种球蛋白对川崎病患儿炎症反应及氧化应激反应的影响

目的探讨静脉注射丙种球蛋白(IVIG)对川崎病患儿炎症反应及氧化应激反应的影响。方法选取90例川崎病的患儿,随机分为A组、B组、C组,每组30例。A组静脉注射IVIG 1g/(kg·d),B组IVIG 2 g/(kg·d),C组IVIG3 g/(kg·d)。比较3组的症状缓解情况、炎症反应、氧化应激、冠脉损伤及不良反应。结果 B组和C组的临床症状的消退时间、住院时间均显著短于A组(P0.05),TNF-α、IL-6、IL-10、MDA均显著低于A组(P0.05),SOD、GSH-Px显著高于A组(P0.05)。A组冠脉损伤的发生率显著高于B组和C组(P0.05)。结论 IVIG 2 g/(kg·d)剂量能显著缓解川崎病患儿的炎症反应和氧化应激损伤,减少冠脉损伤。     

Glutathione, vitamin E and oxidative stress in coronary artery disease: relevance of age and gender

Background  Observational studies suggest that low levels of antioxidants are associated with high risk for coronary artery disease (CAD). We investigated whether the biomarkers of oxidative balance undergo the same modifications in all CAD patient groups, regardless of gender and age.
Materials and methods  One hundred sixty-eight CAD patients and 107 healthy controls were assayed for plasma levels of reduced glutathione (GSH), α- and γ-tocopherol (α- and γ-T) as endogenous antioxidants. A damage score (DS), representative of oxidative stress status, was calculated. ancova models were used to test the association between antioxidants, DS and CAD and its modulation by age and gender.
Results  The DS was higher in CAD than in controls. GSH levels, were lower in CAD patients (mean ± SEM: 57·61 ± 1·87 μmol 10 g⁻¹ haemoglobin vs. 68·55 ± 2·23 in controls, P  < 0·0006) in males and in older subjects. Levels of other antioxidants exhibited a complex pattern. Overall, no difference was found in α- and γ-T contents between CAD and controls, but lower α-T values were observed in CAD females. A significant interaction between CAD status and gender was observed ( P  = 0·003).
Conclusions  Our study shows that the involvement of antioxidants in CAD is related to patients' characteristics. These findings may be relevant in planning antioxidant therapies.     

Dietary phosphate restriction ameliorates endothelial dysfunction in adenine-induced kidney disease rats

Hyperphosphatemia causes endothelial dysfunction as well as vascular calcification. Management of serum phosphate level by dietary phosphate restriction or phosphate binders is considered to be beneficial to prevent chronic kidney disease patients from cardiovascular disease, but it has been unclear whether keeping lower serum phosphate level can ameliorate endothelial dysfunction. In this study we investigated whether low-phosphate diet can ameliorate endothelial dysfunction in adenine-induced kidney disease rats, one of useful animal model of chronic kidney disease. Administration of 0.75% adenine-containing diet for 21 days induced renal failure with hyperphosphatemia, and impaired acetylcholine-dependent vasodilation of thoracic aortic ring in rats. Then adenine-induced kidney disease rats were treated with either control diet (1% phosphate) or low-phosphate diet (0.2% phosphate) for 16 days. Low-phosphate diet ameliorated not only hyperphosphatemia but also the impaired vasodilation of aorta. In addition, the activatory phosphorylation of endothelial nitric oxide synthase at serine 1177 and Akt at serine 473 in the aorta were inhibited by in adenine-induced kidney disease rats. The inhibited phosphorylations were improved by the low-phosphate diet treatment. Thus, dietary phosphate restriction can improve aortic endothelial dysfunction in chronic kidney disease with hyperphosphatemia by increase in the activatory phosphorylations of endothelial nitric oxide synthase and Akt.     

Increased blood oxidative stress in experimental menopause rat model: the effects of vitamin A low-dose supplementation upon antioxidant status in bilateral ovariectomized rats

Menopause has been reported to be associated with increased oxidative stress and metabolic disorders among women worldwide. Disarrangements in the redox state similar to those observed in women during the decline of ovarian hormonal activity can be obtained experimentally through rat bilateral ovariectomy. The search for alternative treatments to improve life quality in postmenopausal woman is really important. The aim of this study was to evaluate biochemical and oxidative stress parameters that distinguish sham-operated female rats from Wistar rats bilaterally ovariectomized (OVX). Additionally, we have also investigated the effects of retinol palmitate (a vitamin A supplement) low-dose supplementation (500 or 1500 IU/kg/day, during 30 days) upon blood and plasma antioxidant status in OVX rats. Ovariectomy caused an increase in body weight gain, pronounced uterine atrophy, decreased plasma triglycerides and increased total cholesterol levels, and reduced acid uric content. Moreover, we found increased blood peroxidase activities (catalase and glutathione peroxidase), decreased plasma non-enzymatic antioxidant defenses total reactive antioxidant potential and total antioxidant reactivity, decreased protein and non-protein SH levels, accompanied by increased protein oxidative damage (carbonyl). In addition, vitamin A low-dose supplementation was capable to ameliorate antioxidant status in OVX rats, restoring both enzymatic and non-enzymatic defenses, promoting reduction in plasma SH content, and decreasing protein oxidative damage levels. This is the first work in the literature showing that vitamin A at low dose may be beneficial in the treatment of menopause symptoms. Further studies will be made to better understand the effects of vitamin A supplementation in menopause rat model.     

大鼠酒精性肝病细胞凋亡与细胞色素P450 2E1和氧化应激的关系

目的 观察酒精性肝病(ALD)大鼠肝组织病理学改变,探讨细胞凋亡与细胞色素P4502E1(CYP2E1)的表达以及与氧化应激的关系.方法 用乙醇灌胃法制备ALD大鼠模型,模型组(37只)给予体积分数为40%的乙醇8 g·kg-1·d-1分两次灌胃,连续8周;对照组(33只)给予等量生理盐水灌胃.实验第8周末,各组选30只大鼠观察肝组织的病理学改变;用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测肝细胞凋亡,用全自动生化仪检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)值,用聚合酶链反应(PCR)法测定肝CYP2E1的表达;分别用硫代巴比妥酸法和黄嘌呤氧化酶法测定血清丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性.结果 模型组凋亡的肝细胞明显增多,主要分布在中央静脉周围、点状和灶状坏死区.对照组CYP2E1的c1基因频率为91.65%、c2基因频率为8.35%;模型组c1基因频率为53.35%、c2基因频率为46.65%,差异均有显著性(P均＜0.05).长期摄入乙醇的大鼠血清MDA含量增加,SOD活性下降,与ALD肝细胞凋亡程度有相关性(rMDA=0.644,rSOD=-0.511,P均＜0.05),且MDA与SOD两指标间呈负相关(r=-0.582,P＜0.05).结论 长期摄入乙醇可引起大鼠ALD及肝功能损伤,肝细胞凋亡明显增加.CYP2E1基因PstⅠ及RsaⅠ限制性片段长度多态性与ALD有关,其中c2基因可能与大鼠ALD的发生有关.MDA含量和SOD活性在ALD的肝细胞凋亡过程及脂质过氧化反应中发挥重要作用.     

The effect of diminazene,an angiotensin-converting enzyme 2 activator,on adenine-induced chronic kidney disease in rats

The present study investigated the effect of diminazene, lisinopril, or valsartan on adenine-induced chronic kidney disease (CKD) in rats. The animals were divided into five groups (n = 6). The first and second groups received normal diet and adenine in the feed at a dose of 0.25% w/w for 35 days, respectively. The third, fourth, and fifth groups were treated as the second group but also received diminazene (15 mg/kg/day), lisinopril (10 mg/kg/day), and valsartan (30 mg/kg/day), respectively, for 35 days. Adenine significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), calcium, phosphorus, and uric acid. In addition, adenine increased urinary albumin/creatinine ratio and N-Acetyl-β-D-glucosaminidase (NAG)/creatinine ratio and reduced creatinine clearance. Adenine also significantly increased the plasma concentrations of inflammatory cytokines (plasma tumor necrosis factor–alpha [TNF-α] and interleukin-1beta [IL-1β]) and significantly reduced antioxidant indices (catalase, glutathione reductase [GR], and superoxide dismutase [SOD]). Histopathologically, renal tissue from adenine-treated rats showed necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. All drugs ameliorated adenine-induced biochemical and histopathological changes. The protective effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Our results show that administration of diminazene, lisinopril, or valsartan had a comparable effect on the reversal of the biochemical and histopathological indices of adenine-induced CKD in rats.     

Increased antioxidant capacity in healthy volunteers taking a mixture of oral antioxidants versus vitamin C or E supplementation

The objectives of this study were (1) to evaluate the capacity of human plasma that had been obtained from healthy adult volunteers before and after they ingested vitamin E or C to inhibit induced lipoperoxidation in vitro (antioxidant capacity of plasma [ACP]), and (2) to compare the efficiency of these vitamins with that of a commercial mixture of antioxidant vitamins, cofactors, and minerals (MAOx). Seventy-nine healthy individuals between 19 and 23 y of age were randomly assigned to 1 of 4 groups. Each received a daily dose of antioxidants for 7 d: vitamin C (n=18; 500 mg), vitamin E (n=21; 400 IU), vitamins C and E (n=19), or MAOx (n=21; 1.2 g). ACP and plasma malondialdehyde were measured at 4 and 24 h and 7 d. ACP increased significantly (P<.05) in all 4 groups within 4 h of antioxidant intake, and this effect was sustained throughout supplementation. Plasma ACP increased significantly over basal values in the group taking MAOx; relative increases were 42%, 44%, and 55% at 4 h, 24 h, and 7 d, respectively (P<.001). Smaller increases in plasma ACP were observed in the vitamin C group (25%, 32%, and 36%) and, specifically, in the vitamin E group (17%, 24%, and 28%) (P<.05). The mixture of vitamins and minerals was comparatively more efficient than vitamin C or E alone, presumably because MAOx contains various antioxidant compounds with different redox potentials, leading to the possible development of chain reactions.