高通量血液透析联合左卡尼汀对老年维持性血液透析患者免疫功能、氧化应激和微炎症状态的影响

摘要 目的：观察高通量血液透析（HFHD）联合左卡尼汀在老年维持性血液透析（MHD）患者中的应用效果。方法：选择我院2020年1月~2021年2月间接收的100例老年MHD患者。采用随机数字表法将患者分为对照组（50例,接受HFHD治疗）和研究组（50例,接受HFHD联合左卡尼汀治疗）,均治疗3个月。观察两组免疫功能、氧化应激、微炎症状态、其他血生化指标和治疗安全性。结果：与对照组相比,研究组治疗3个月后CD3⁺、CD4⁺、CD4⁺/CD8⁺更高,CD8⁺更低（P<0.05）。与对照组相比,研究组治疗3个月后血清白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、超敏C反应蛋白（hs-CRP）水平更低（P<0.05）。与对照组相比,研究组治疗3个月后血清超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）水平更高,丙二醛（MDA）水平更低（P<0.05）。与对照组相比,研究组治疗3个月后血红蛋白（Hb）、红细胞比容（Hct）、前白蛋白（PA）更高（P<0.05）。两组三酰甘油（TG）、总胆固醇（TC）组内治疗前、治疗3个月后以及组间对比统计学无意义（P>0.05）。与对照组相比,研究组不良反应总发生率更低（P<0.05）。结论：HFHD联合左卡尼汀可有效改善老年MHD患者免疫功能,改善机体营养状态,减轻氧化应激和微炎症状态,降低不良反应发生率,且对机体血脂代谢影响轻微。     

不同铁剂对血液透析患者贫血、炎症及氧化应激状态的影响

目的:探讨口服铁剂和静脉铁剂对维持性血液透析患者贫血、炎症及氧化应激状态的影响.方法:选择在深圳市福田区人民医院血液净化中心透析龄超过3个月的MHD患者24例,分别给予口服铁剂和静脉铁剂,进行为期8周随访,分别检测治疗前、治疗4周、治疗8周后患者的血红蛋白(hemoglobin,Hb)、红细胞比容(hematocrit,Hct)、血清铁(seruin iron,SI)、铁蛋白(serum ferritin,SF)、血清转铁蛋白饱和度(transferrinsaturation,TSAT),C-反应蛋白(C-reactive protein,CRP)、IL-6、TNF-α以及血浆丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、血浆谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px).结果:(1)4周时,A组患者Hb、HCT及铁蛋白均较治疗前升高,差异有统计学意义(P＜0.05);8周时,两组Hb、HICT、铁蛋白较治疗前均升高,A组较B组相比显著升高(P＜0.05).A组TSAT较治疗前及B组均显著升高;B组治疗前后TSAT无显著改变;血清铁在A、B两组治疗后无显著改变.(2)CRP、IL-6在口服或静脉补铁期间变化均无显著性(P＞0.05),TNF-α在静脉铁刺治疗8周后较前及口服铁剂8周后相比,有显著升高(P＜0.05).(3)4周时,A组患者MDA水平较治疗前及B组均显著上升,SOD、GSH-Px水平显著低于治疗前及B组,其差异有显著性(P＜0.05);8周时恢复至治疗前水平.B组治疗过程中未发现MDA、SOD、GSH-Px水平的明显改变.结论:静脉铁剂在改善贫血及缺铁状态的效果优于口服补铁,但短期会诱导炎症及氧化应激反应的加剧.     

血液透析联合血液透析滤过对患者营养及微炎症指标的影响

目的:探讨血液透析(HD)联合血液透析滤过(HDF)对维持性血液透析(MHD)患者营养及微炎症指标的影响。方法:选择2005年12月到2014年12月在我院接受治疗的140例MHD患者,随机分为HD组(n=70)和HD+HDF组(n=70)。比较两组患者治疗前后营养不良-炎症评分(MIS)、C反应蛋白(CRP)、白细胞介素6(IL-6)、白蛋白(ALB)、前白蛋白(PA)、血红蛋白(Hb)、握力(HS)、肱三头肌皮褶厚度(TSF)的变化。结果:治疗后,HD+HDF组患者MIS明显降低,ALB、PA、Hb、HS、TSF明显升高(均P0.05),且各指标改善程度均优于HD组(均P0.05);治疗后,HD+HDF组患者相比于治疗前和HD组治疗后,CRP、IL-6明显降低(均P0.05)。结论:HD联合HDF较单纯HD能更好的改善患者营养状态,减轻微炎症反应。     

高通量与低通量血液透析对糖尿病肾病透析患者氧化应激、细胞免疫功能和微炎症状态的影响

目的:比较高通量与低通量血液透析对糖尿病肾病透析患者氧化应激、细胞免疫功能和微炎症状态的影响。方法:选择2011年1月~2017年1月在我院进行诊治的糖尿病肾病透析患者60例,随机分为对照组与观察组,每组各30例。对照组采用低通量血液透析治疗,观察组采用高通量血液透析治疗,两组每次血液透析的时间、透析液流速以及透析液成分均完全相同。比较两组血液透析前后的血清丙二醛、过氧化物歧化酶以及谷胱甘肽过氧化物酶等氧化应激指标,CD~+4、CD~+3、CD~+8以及CD~+4/CD~+8等细胞免疫功能指标,高敏C反应蛋白、白介素-6以及肿瘤坏死因子等微炎症状态指标。结果:治疗后,观察组血清过氧化物歧化酶、谷胱甘肽过氧化物酶、高敏C反应蛋白、白介素-6以及肿瘤坏死因子水平均明显低于对照组(P0.05),血清丙二醛、CD~+4、CD~+3以及CD~+4/CD~+8水平均明显高于对照组(P0.05)。结论:糖尿病肾病血液透析患者体内普遍存在不同程度的微炎症状态以及氧化应激状态,长期采用低通量血液透析会加重体内的炎性反应和氧化应激水平,而高通量血液透析能缓解炎性反应和氧化应激,并且有效改善患者的细胞免疫功能。     

慢性炎症与动脉粥样硬化关系的研究进展

动脉粥样硬化(atherosclerosis,AS)的发病机制非常复杂,对其研究经历了一个半世纪,直到1999年Ross提出"动脉粥样硬化是一种炎症性疾病",各种炎症细胞和炎症因子参与动脉粥样硬化的发生和发展过程。已有众多的基础和临床研究都证实炎症在AS中的重要作用,但仍需要对AS发生发展的深入研究,使我们更准确认识和有效的防治AS。本文就近年来慢性炎症与动脉粥样硬化关系的研究进展作一综述。     

慢性炎症与动脉粥样硬化关系的研究进展

动脉粥样硬化（atherosclerosis,AS）的发病机制非常复杂,对其研究经历了一个半世纪,直到1999年Ross提出”动脉粥样硬化是一种炎症性疾病”,各种炎症细胞和炎症因子参与动脉粥样硬化的发生和发展过程。已有众多的基础和临床研究都证实炎症在AS中的重要作用,但仍需要对AS发生发展的深入研究,使我们更准确认识和有效的防治AS。本文就近年来慢性炎症与动脉粥样硬化关系的研究进展作一综述。     

炎症与动脉粥样硬化及冠状动脉疾病的关系

炎症在冠状动脉疾病和其他动脉粥样硬化性疾病中起着重要作用.在动脉粥样硬化早期病变处存在大量的免疫细胞,它们所分泌的一系列细胞因子加速病变的进程,激活炎症反应导致急性冠脉综合症的发生.动脉粥样硬化,是冠状动脉疾病的主要病因,是一种炎性疾病,炎症因子参与到免疫反应过程中,使得动脉壁处的病变得以发生、蔓延和活化.     

厄贝沙坦联合左卡尼汀对维持性血液透析患者微炎症反应和营养状况的影响

目的:探讨厄贝沙坦和左卡尼汀对维持性血液透析(MHD)患者炎症因子和营养指标的改善作用。方法:选择2013年1月至2014年6月在我院血液透析中心接受MHD的终末期肾脏病患者120例为研究对象,依据随机数字表分成单纯透析组、厄贝沙坦组、左卡尼汀组和联合用药组,各30例,分别接受单纯透析治疗,口服厄贝沙坦0.15-0.3g/d,静脉推注左卡尼汀1g/次,厄贝沙坦和左卡尼汀联合治疗。检测治疗前,治疗3、6个月后血清中C反应蛋白(CRP)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)转化生长因子(TGF)水平及营养状况指标的变化。结果:治疗3个月后,厄贝沙坦组、左卡尼汀组及联合用药组CRP、IL-8和TGF的水平与治疗前及单纯透析组比较均有明显下降(P0.05),治疗6个月后,厄贝沙坦组、左卡尼汀组及联合用药组CRP、IL-8、IL-10和TGF水平较治疗前及纯透析组均明显下降(P0.05),且联合用药组下降程度显著高于厄贝沙坦组和左卡尼汀组(P0.05)。治疗6个月后,左卡尼汀组及联合用药组血清红蛋白(Hb)、血清白蛋白(Alb)、前白蛋白(PA)水平较治疗前及单纯透析组显著升高(P0.05),联合用药组血清Hb、Alb和PA水平上升更明显,差异均有统计学意义(P0.05)。结论:厄贝沙坦联合左卡尼汀既能缓解MHD患者的微炎症反应,又能改善其营养状况。     

维持性透析患者体内氧化应激状态及影响因素研究

目的:探讨慢性肾脏病5D期(Chronic Kidney Disease stage 5D,CKD5D)患者体内氧化应激水平变化及相关影响因素,比较不同的肾替代治疗方式对终末期肾病患者体内氧化应激水平的影响。方法:收集CKD5D期患者血清,采用双抗体夹心法测定血清超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽-过氧化物酶(GSH-Px)水平,同时收集患者临床资料,用统计学方法进行相关影响因素分析。结果:透析患者体内氧化应激水平明显高于正常对照组(P0.05)。维持性血液透析患者氧化应激水平高于腹膜透析患者(P0.05)。多因素回归分析结果提示:CKD5D期患者体内氧化应激水平与透析方式、透析时间、性别、年龄、是否贫血、他汀类药物、血管紧张素转化酶抑制剂/血管紧张素II受体阻滞剂(ACEI/ARB)类药物的使用及CRP密切相关(P0.05)。而铁剂、重组人促红细胞生成素(EPO)的使用和白细胞计数与氧化应激水平无独立相关性(P0.05)。结论:CKD5D期患者体内氧化应激水平与透析方式、透析龄和性别相关,维持性血液透析患者体内氧化应激水平高于维持性腹膜透析患者。     

尿毒症维持性血液透析患者衰弱的影响因素分析及其对认知功能和微炎症状态的影响

摘要 目的：探讨尿毒症维持性血液透析（MHD）患者衰弱的影响因素,分析其对认知功能和微炎症状态的影响。方法：回顾性分析2020年4月~2022年7月期间江苏省人民医院收治的105例尿毒症MHD 患者的临床资料,根据衰弱评分将患者分为无衰弱组（n=38）、衰弱前期组（n=34）、衰弱组（n=33）。根据病例资料获取患者的一般资料和实验室资料,对比三组一般资料和实验室资料、认知功能情况;采用多因素Logistic回归分析尿毒症MHD患者衰弱的影响因素。结果：无衰弱组、衰弱前期组、衰弱组的年龄、透析龄、吸烟史、饮酒史、运动情况、合并症、白蛋白（ALB）、血红蛋白（Hb）、前白蛋白（PA）、尿素氮（BUN）、血肌酐（Scr）、25-羟维生素D[25-（OH）D]、甲状旁腺激素（PTH）组间对比有差异（P<0.05）。衰弱组的C反应蛋白（CRP）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）高于无衰弱组、衰弱前期组,且衰弱前期组高于无衰弱组（P<0.05）。衰弱组的简易精神状态检查量表（MMSE）评分低于无衰弱组、衰弱前期组,且衰弱前期组低于无衰弱组（P<0.05）。衰弱组的认知功能障碍（POCD）发生率高于无衰弱组、衰弱前期组,且衰弱前期组高于无衰弱组（P<0.05）。多因素Logistic回归分析结果显示：并发症、ALB偏低、Hb偏低、PA偏低、25-（OH）D偏低、CRP偏高、IL-6偏高、TNF-α偏高、MMSE评分偏低是尿毒症MHD患者衰弱危险因素,而经常运动是其保护因素（P<0.05）。结论：尿毒症MHD患者衰弱的发生率较高,可导致患者认知功能下降,微炎症程度升高,与并发症、ALB、Hb、PA、25-（OH）D、CRP、IL-6、TNF-α、MMSE评分、运动情况等多种因素相关。     

Ceramide in apoptosis signaling: relationship with oxidative stress

Ceramide is one of the major sphingosine-based lipid second messengers that is generated in response to various extracellular agents. However, while widespread attention has focused on ceramide as a second messenger involved in the induction of apoptosis, important issues with regard to the mechanisms of ceramide formation and mode of action remain to be addressed. Several lines of evidence suggest that ceramide and oxidative stress are intimately related in cell death induction. This review focuses on the putative relationships between oxidative stress and sphingolipid metabolism in the apoptotic process and discusses the potential mechanisms that connect and regulate the two phenomena.     

Evaluation of oxidative stress in patients with cancer

The oxidative stress is considered to be involved in the pathophysiology of cancers. In the current study we explored the oxidative stress in patients with different cancers and corresponding benign diseases by evaluation of the level of lipid peroxidation products (MDA level) in the plasma and the activity of erythrocyte antioxidant defense enzymes superoxide dismutase (SOD) and catalase (CAT). Significantly higher plasma levels of lipid peroxidation products were detected in patients with early and advanced cancers in comparison to the healthy volunteers (mean 3.1 micromol/l and 2.3 micromol/l, p = 0.0003 and p = 0.029, respectively, t-test). In addition, 10-20 days after radical operations of cancer patients with normal postoperative recovery period, the plasma levels of MDA decreased and reached values close to the controls (mean 2.0 micromol/l). SOD in erythrocytes of patients with benign diseases and malignant solid tumors before and after surgery did not differ from that of the controls. In contrast, CAT activity of patients with early cancers was found to be significant higher than that of the controls (mean 22157.2 U/gHb vs. 12832.0 U/gHb, p = 0.032, t-test). A decrease of CAT activity was observed after surgery (mean 15225.0 U/gHb). In conclusion, our results suggest the presence of an increased oxidative stress accompanied by a lack of changes of erythrocyte SOD activity and an adaptive increase of CAT activity.     

The relationship between excitotoxicity and oxidative stress in the central nervous system

Excitotoxicity and oxidative stress are two phenomena that have been repeatedly described as being implicated in a wide range of disorders of the nervous system. Such disorders include several common idiopathic neurological diseases, traumatic brain injury, and the consequences of exposure to certain neurotoxic agents. While there is evidence that metabolic derangements can laed to these adverse processes, and that these processes may synergize in their damaging effects, the degree of interdependence, and the causal relation between them is not clear. The intent of this review is to delineate potential mechanisms which may unit hyperexcitation to the excessive generation of reactive oxygen species. The degree of linkage between these events appears rather strong. It is likely that excitoxicity frequency leads to a pro-oxidant condition but that high rates of generation of reactive oxygen species are not invariably accompanied by a hyperexcited neuronal state Both excitoxic and ‘oxidotoxic’ states result from the failure of normal compensatory anti excitatory and antioxidant mechanisms to maintain cellular homeostatis.     

The association between oxidative stress and obstructive lung impairment in patients with COPD

An oxidant/antioxidant imbalance is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that antioxidant capacity reflected by erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities, and serum levels of the lipid peroxidation product malondialdehyde (MDA), may be related to the severity of obstructive lung impairment in patients with COPD. Erythrocyte GPx, SOD and CAT activities, and serum levels of MDA were measured in 79 consecutive patients with stable COPD. Pulmonary functional tests were assessed by body plethysmography. Moderate COPD (FEV1 50-80%) was present in 23, and severe COPD (FEV1 < 50%) in 56 patients. Erythrocyte GPx activity was significantly lower, and serum MDA levels were significantly higher in patients with severe COPD compared to patients with moderate COPD (GPx: 43.1+/-1.5 vs. 47.7+/-2.9 U/gHb, p<0.05, MDA: 2.4+/-0.1 vs. 2.1+/-0.1 nmol/ml, p<0.05). Linear regression analysis revealed a significant direct relationship between FEV1 and erythrocyte GPx activity (r = 0.234, p<0.05), and a significant inverse relationship between FEV1 and serum MDA levels (r = -0.239, p<0.05). However, no differences were observed in the erythrocyte SOD and CAT activities between the two groups of patients with different severity of COPD. Findings of the present study suggest that antioxidant capacity reflected by erythrocyte GPx activity and serum levels of the lipid peroxidation product MDA are linked to the severity of COPD.     

Tryptophan metabolism and oxidative stress in patients with Huntington's disease

Abnormalities in the kynurenine pathway may play a role in Huntington's disease (HD). In this study, tryptophan depletion and loading were used to investigate changes in blood kynurenine pathway metabolites, as well as markers of inflammation and oxidative stress in HD patients and healthy controls. Results showed that the kynurenine : tryptophan ratio was greater in HD than controls in the baseline state and after tryptophan depletion, indicating increased indoleamine dioxygenase activity in HD. Evidence for persistent inflammation in HD was provided by elevated baseline levels of C-reactive protein, neopterin and lipid peroxidation products compared with controls. The kynurenate : kynurenine ratio suggested lower kynurenine aminotransferase activity in patients and the higher levels of kynurenine in patients at baseline, after depletion and loading, do not result in any differences in kynurenic acid levels, providing no supportive evidence for a compensatory neuroprotective role for kynurenic acid. Quinolinic acid showed wide variations in blood levels. The lipid peroxidation data indicate a high level of oxidative stress in HD patients many years after disease onset. Levels of the free radical generators 3-hydroxykynurenine and 3-hydroxyanthranilic acid were decreased in HD patients, and hence did not appear to contribute to the oxidative stress. It is concluded that patients with HD exhibit abnormal handling of tryptophan metabolism and increased oxidative stress, and that these factors could contribute to ongoing brain dysfunction.     

The relationship between glycemia, insulin and oxidative stress in hereditary hypertriglyceridemic rat

The aim of this study was to determine the effects of insulin infusion on oxidative stress induced by acute changes in glycemia in non-stressed hereditary hypertriglyceridemic rats (hHTG) and Wistar (control) rats. Rats were treated with glucose and either insulin or normal saline infusion for 3 hours followed by 90 min of hyperglycemic (12 mmol/l) and 90 min of euglycemic (6 mmol/l) clamp. Levels of total glutathione (GSH), oxidized glutathione (GSSG) and total antioxidant capacity (AOC) were determined to assess oxidative stress. In steady states of each clamp, glucose infusion rate (GIR) was calculated for evaluation of insulin sensitivity. GIR (mg.kg(-1).min(-1)) was significantly lower in hHTG in comparison with Wistar rats; 25.46 (23.41 - 28.45) vs. 36.30 (27.49 - 50.42) on glycemia 6 mmol/l and 57.18 (50.78 - 60.63) vs. 68.00 (63.61 - 85.92) on glycemia 12 mmol/l. GSH/GSSG ratios were significantly higher in hHTG rats at basal conditions. Further results showed that, unlike in Wistar rats, insulin infusion significantly increases GSH/GSSG ratios in hHTG rats: 10.02 (9.90 - 11.42) vs. 6.01 (5.83 - 6.43) on glycemia 6 mmol/l and 7.42 (7.15 - 7.89) vs. 6.16 (5.74 - 7.05) on glycemia 12 mmol/l. Insulin infusion thus positively influences GSH/GSSG ratio and that way reduces intracellular oxidative stress in insulin-resistant animals.     

The relationship between dose of vitamin E and suppression of oxidative stress in humans

The oxidation hypothesis of atherogenesis has been the focus of much research over the past 2 decades. However, randomized placebo-controlled trials evaluating the efficacy of vitamin E in preventing cardiovascular events in aggregate have failed to show a beneficial effect. Implicit in these trials is that the dose of vitamin E tested effectively suppressed oxidative stress status but this was never determined. We defined the dose-dependent effects of vitamin E (RRR-alpha-tocopherol) to suppress plasma concentrations of F2-isoprostanes, a biomarker of free radical-mediated lipid peroxidation, in participants with polygenic hypercholesterolemia and enhanced oxidative stress, a population at risk for cardiovascular events. A time-course study was first performed in participants supplemented with 3200 IU/day of vitamin E for 20 weeks. A dose-ranging study was then performed in participants supplemented with 0, 100, 200, 400, 800, 1600, or 3200 IU/day of vitamin E for 16 weeks. In the time-course study, maximum suppression of plasma F2-isoprostane concentrations did not occur until 16 weeks of supplementation. In the dose-ranging study there was a linear trend between the dosage of vitamin E and percentage reduction in plasma F2-isoprostane concentrations which reached significance at doses of 1600 IU (35+/-2%, p<0.035) and 3200 IU (49+/-10%, p<0.005). This study provides information on the dosage of vitamin E that decreases systemic oxidant stress in vivo in humans and informs the planning and evaluation of clinical studies that assess the efficacy of vitamin E to mitigate disease.     

Study on oxidative stress in patients with abdominal trauma

Reactive oxygen species have been implicated in the etiology of multiple organ dyspepsia syndrome and infection's complications in patients with trauma. But the oxidative stress and antioxidants levels in abdominal trauma have not yet been studied. Therefore, this study was planned to measure lipid peroxidation for oxidative stress and reduced glutathione, catalase and superoxide dismutase (SOD) for antioxidant levels in plasma & heamolysate of 30 patients with abdominal trauma and 30 controls. From this study we can summarize that there was an increase in oxidative stress and decrease in antioxidant levels (causing oxidative stress) on day zero in patients with abdominal trauma. This oxidative stress on day zero was not related to the development of complications. There was no significant difference in oxidative stress between patients with solitary and multiple abdominal organ injury and also between patients with hollow viscus injury and solid organ injury on day zero. From this study, we conclude that in patients with abdominal trauma there was increase in oxidative stress and decrease in antioxidant levels on day zero.     

The evaluation of the oxidative stress parameters in patients with primary angle-closure glaucoma

Objective

To clarify the presence of oxidative stress in patients with primary angle-closure glaucoma (PACG) and to investigate the relationship between oxidative stress and PACG.

Methods

Fifty patients with primary angle-closure glaucoma and fifty healthy controls of matched age and gender were included in the study prospectively. Serum samples were obtained to detect the oxidation degradation products malondialdehyde (MDA), conjugated diene (CD), 4-hydroxynonenal (4-HNE), advanced oxidation protein products (AOPP), protein carbonyl (PC), ischemia-modified albumin (IMA) and 8-hydroxydeoxyguanosin (8-OHdG).

Results

The concentration of MDA and CD in PACG patients was significantly higher than those of the control subjects (P<0.05, P<0.01). The serum 4-HNE concentrations were increased in PACG patients, but the differences with those of the healthy controls were not statistically significant. Compared to normal subjects, there was significant higher in serum AOPP and PC in PACG patients (P<0.01). PACG patients had higher levels of 8-OHdG in serum with respect to the comparative group of normal subjects (P<0.01). When plasma IMA levels in the PACG group were compared with those in the control group, significant increases in IMA were observed in the former (P<0.05).

Conclusions

Our study demonstrated that IMA is a new biomarker available for assessing oxidative stress in PCAG. Oxidative stress is an important risk factor in the development of primary angle-closure glaucoma. Increased levels of oxidative stress products may be associated with primary angle-closure glaucoma.