氧化应激与糖尿病

高血糖引起的自由基产生过多或消除障碍导致氧化应激的出现,氧化应激与糖尿病及其并发症的发生发展密切相关。抗氧化治疗为糖尿病及并发症的防治提供了新的思路。     

氧化应激与糖尿病性心肌病的发生发展

糖尿病患者经常表现出一种独特的心脏表型,即糖尿病性心肌病（Diabetic cardiomyopathy,DCM）。由于在糖尿病患者中慢性炎症和氧化应激的发生,改变了机体代谢稳态,引发氧化还原失衡,从而诱发心肌代谢紊乱和心脏微血管病变,使心脏出现危险的氧化应激,致使了糖尿病性心肌病的发生。心肌细胞中脂肪的氧化与毒性增加以及微脉管系统中高水平的细胞血糖,让糖尿病患者体内的线粒体产生过量的活性氧（reactive oxygen species, ROS）。超氧阴离子自由基可增强己糖胺生物合成途径和多元醇通路,诱导活化蛋白激酶C(protein kinase C, PKC),增加晚期糖基化终产物（advanced glycation end products, AGEs）的形成并激活其受体（receptor for advanced glycation end products, RAGE）。这些生化级联反应同时也是ROS的其他额外来源。本文主要概述氧化应激在DCM中的作用及其涉及信号通路。同时,也简要提到了目前用于DCM的治疗方法。基于氧化应激在糖尿病性心肌病中的关键作用,新的抗氧化疗法的...     

氧化应激与2型糖尿病

胰岛素抵抗、胰岛β细胞功能受损是2型糖尿病的主要病因。高血糖、高血脂导致在代谢过程中,线粒体产生大量活性氧,其可损坏线粒体功能,引起氧化应激反应。氧化应激可以激活细胞内的一系列应激信号通路,如JNK／SAPK、p38MAPK、IKKβ／NF-kβ和氨基己醣通路等。这些应激通路的激活可以产生以下结果：（1）阻断胰岛素作用通路,导致胰岛素抵抗;（2）降低胰岛素基因表达水平;（3）抑制胰岛素分泌;（4）促进β细胞凋亡等。本文主要针对活性氧的产生、氧化应激诱导胰岛素抵抗和胰岛β细胞功能受损等机制加以综述,以便进一步阐明2型糖尿病的发病机理。     

氧化应激与2型糖尿病的研究进展

氧化应激与2型糖尿病(T2DM)的发生、发展密切相关.胰岛素抵搞(Insulin Resistance,IR)、胰岛β细胞功能受损是2型糖尿病的主要病因.而氧化应激可以直接及间接激活细胞内的一系列应激信号通路,如核因子κ-B(Nuclear factor-KappaB,NF-κB)、c-Jun氨基端激酶(NH-terminal Jun kinase,JNK)、蛋白激酶C(protein kinase C,PKC)、p38丝裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)等.这些应激通路的激活可以产生以下结果:(1)阻断胰岛素作用通路,导致胰岛素抵抗;(2)降低胰岛素基因表达水平,致胰岛素合成和分泌减少;(3)促进胰岛β细胞凋亡等.本文针对氧化应激诱导胰岛素抵抗和胰岛β细胞功能受损等机制加以综述,以便进一步阐明2型糖尿病的发病机制.     

普罗布考对糖尿病大鼠肾组织氧化应激的影响

目的研究普罗布考（Probucol）对糖尿病大鼠肾组织氧化应激的影响。方法采用腹腔注射链脲佐菌素（STZ）建立糖尿病大鼠模型。30只Wistar大鼠分为正常对照组（NC）、糖尿病组（DM）、糖尿病普罗布考治疗组（DP）。8周末称取体重、肾重、计算肾肥大指数（肾重/体重）,检测尿白蛋白排泄率（UAER）;测定各组生化指标包括血糖（BG）、胆固醇（TC）、三酰甘油（TG）、血清肌酐（SCr）、血尿素氮（BUN）;检测肾组织中丙二醛（MDA）的含量及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）与谷胱甘肽过氧化物酶（GSH-Px）活性;肾组织切片行PAS染色分析肾小球面积及肾小球体积。结果 DM组大鼠肾重、肾重/体重、UAER、TC、TG、SCr、BUN、肾小球面积、肾小球体积较NC组均明显增加,DP组上述改变较DM组均明显减轻（P〈0.05）。DP组肾组织中MDA含量明显低于DM组,SOD、CAT、GSH-Px活性明显高于DM组（P〈0.05）。结论普罗布考可能部分通过减轻肾组织氧化应激反应实现对糖尿病大鼠肾脏的保护作用。     

运动介导氧化应激改善糖尿病性心肌病的研究进展

随着糖尿病患病率日趋增加,糖尿病性心肌病(diabetic cardiomyopathy,DCM)也越来越受到关注.糖尿病性心肌病的致病因素很多,氧化应激是DCM的重要风险因素,慢性高血糖通过产生大量活性氧(Ros)损伤抗氧化防御系统和增加氧化应激导致心肌病理异常.已有研究证实运动可以降低糖尿病活性氧簇生成、增强抗氧化...     

糖、脂代谢及氧化应激与糖尿病肾病的相关性

糖尿病肾病是糖尿病的主要并发症之一。近年来,糖尿病肾病的发病率呈逐渐上升趋势。研究发现,糖、脂代谢与糖尿病肾病的发生密切相关,而氧化应激也在糖、脂代谢异常中起重要作用。本文综述了有关糖、脂代谢与糖尿病肾病相关性研究,以及硫氧还蛋白及硫氧还蛋白结合蛋白2在糖尿病肾病发生中的作用。     

妊娠期糖尿病患者体内铁负荷状态及氧化应激水平的研究

为了探讨铁代谢在妊娠期糖尿病(GDM)发病中的作用,对GDM患者体内铁负荷状态、氧化应激水平及抗氧化状态进行分析研究.在912例孕24～28周产前检查的孕妇中,按血糖筛查和糖耐量试验筛选出GDM孕妇32例为实验组,随机选择糖耐量正常孕妇26例作为对照组,分别测定两组孕妇的血红蛋白(Hb)等指标,以评价机体铁代谢状况;测...     

缬沙坦对糖尿病大鼠心肌保护作用以及氧化应激的影响

目的:探讨缬沙坦对糖尿病大鼠心肌的保护作用及氧化应激影响。方法:以链脲佐菌素建立糖尿病大鼠模型,缬沙坦干预治疗12周后,采用ELISA法检测血清中8脱氧鸟酐(8-OHd G)含量、超氧化物歧化酶(SOD)活性,PCR测定心肌NADPH氧化酶亚型NOX2m RNA、p47phox m RNA表达,采用原位末端标记法(TUNEL)检测心肌细胞凋亡。结果:糖尿病大鼠经缬沙坦干预治疗后,8-OHd G含量,NOX2和p47phox m RNA表达均显著降低(P0.05),SOD活性升高(P0.01),心肌细胞凋亡指数显著降低(P0.05)。结论:高血糖导致糖尿病大鼠氧化应激增强和心肌细胞凋亡增加,缬沙坦可降低糖尿病大鼠氧化应激反应及减少心肌细胞凋亡,因而对心肌有一定的保护作用。     

干预脂毒性改善糖尿病大鼠胰岛素分泌及氧化应激的损害

目的探讨干预脂毒性改善糖尿病大鼠胰岛分泌功能及氧化应激损害的机制。方法将大鼠分为4组①正常组（NC）,全程普通饲料喂养;②高脂组（HF）,全程高脂饲料喂养。糖尿病组,高脂饲料喂养8周后腹腔注射低剂量STZ（30mg/kg）,48h后行OGTT试验判断成模情况后分组。③糖尿病对照组（DM）,不给予药物干预;④血脂干预组（SIM）,灌胃辛伐他汀5mg/（kg.d）4周干预脂毒性。通过免疫组化染色观察胰岛B、A细胞形态学特点,RT-PCR测定胰腺内胰岛素原mRNA表达水平,DHE荧光染色检测胰岛中活性氧化产物ROS水平。结果与糖尿病对照组相比,干预脂毒性4周后血清胆固醇（TC）和甘油三酯（TG）水平分别下降了22.9%（P〈0.01）和57.0%（P〈0.05）。OGTT血糖水平均显著下降（P〈0.01）。胰岛中B细胞相对量是对照组的2.6倍（P〈0.01）,B细胞胞质内胰岛素水平增加了26.5%（P〈0.05）,胰岛素原mRNA表达升高18.3%（P〈0.01）;A细胞相对量减少了50%（P〈0.01）。血清丙二醛（MDA）水平和胰腺中ROS表达显著下降。结论辛伐他汀干预脂毒性4周可以显著改善糖尿病大鼠胰岛分泌功能和氧化应激损害。     

Oxidative stress associated to dysfunctional adipose tissue: a potential link between obesity,type 2 diabetes mellitus and breast cancer

Abstract

Diabetes mellitus and breast cancer are two important health problems. Type 2 diabetes (T2DM) and obesity are closely linked with both being associated with breast cancer. Despite abundant epidemiological data, there is no definitive evidence regarding the mechanisms responsible for this association. The proposed mechanisms by which diabetes affects breast cancer risk and prognosis are the same as the mechanisms hypothesised for the contribution of obesity to breast cancer risk. The obesity-induced inflammation promoted by adipose tissue dysfunction is a key feature, which is thought to be an important link between obesity and cancer. Inflammation induces an increase in free radicals and subsequently promotes oxidative stress, which may create a microenvironment favourable to the tumor development in obese persons. Oxidative stress is also proposed as the link between obesity and diabetes mellitus. Therefore, obesity-related oxidative stress could be a direct cause of neoplastic transformation associated with obesity and T2DM in breast cancer cells. This review is focused on the role of obesity-related oxidative stress in the context of chronic inflammation, on the time of breast cancer onset and progression, which provide targets for preventive and therapeutic strategies in the fields of diabetes and obesity-related breast cancer.     

Oxidative stress,erythrocyte ageing and plasma non-protein-bound iron in diabetic patients

Increased oxidative stress and decreased life span of erythrocytes (RBCs) are repeatedly reported in diabetes. In the aim to elucidate the mechanism of the latter, i.e. the events leading to erythrocyte ageing, this study determined in RBCs from diabetic patients iron release in a free desferrioxamine-chelatable form (DCI), methemoglobin (MetHb) formation, binding of autologous IgG to membrane proteins and in plasma non-protein-bound iron (NPBI), F₂-Isoprostanes (F₂-IsoPs) and advanced oxidation protein products (AOPP). DCI and MetHb were higher in diabetic RBCs than in controls and autologous IgG binding occurred in a much higher percentage of diabetic patients than controls. A significant correlation between DCI and IgG binding was found in diabetic RBCs. Plasma NPBI, esterified F₂-IsoPs and AOPP were higher in diabetic patients and a significant correlation was found between plasma NPBI and intra-erythrocyte DCI. The increased DCI and autologous IgG binding appear to be important factors in the accelerated removal of RBCs from the blood stream in diabetes and the increase in plasma NPBI could play an important role in the increased oxidative stress.     

Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: Effect of secoisolariciresinol diglucoside (SDG)

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed has antioxidant activity and has been shown to prevent hypercholesterolemic atherosclerosis. An investigation was made of the effects of SDG on the development of diabetes in diabetic prone BioBreeding rats (BBdp rats), a model of human type I diabetes [insulin dependent diabetes mellitus (IDDM)] to determine if this type of diabetes is due to oxidative stress and if SDG can prevent the incidence of diabetes. The rats were divided into three groups: Group I, BioBreeding normal rats (BBn rats) (n = 10); group II, BBdp untreated (n = 11); and group III, BBdp treated with SDG 22 mg/kg body wt, orally) (n = 14). Oxidative stress was determined by measuring lipid peroxidation product malondialdehyde (MDA) an index of level of reactive oxygen species in blood and pancreas; and pancreatic chemiluminescence (Pancreatic-CL), a measure of antioxidant reserve. Incidence of diabetes was 72.7% in untreated and 21.4% in SDG-treated group as determined by glycosuria and hyperglycemia. SDG prevented the development of diabetes by approximately 71%. Development of diabetes was associated with an increase in serum and pancreatic MDA and a decrease in antioxidant reserve. Prevention in development of diabetes by SDG was associated with a decrease in serum and pancreatic-MDA and an increase in antioxidant reserve. These results suggest that IDDM is mediated through oxidative stress and that SDG prevents the development of diabetes.     

Oxidative stress and differentiation in Neurospora crassa

Environmental stress factors induce oxidative stress in fungi by increasing the intracellular concentrations of reactive oxygen species (ROS). In the mycelium, ROS act as signal molecules needed for cytodifferentiation at certain stages of the development of fungi. Generation of ROS in cells induces the activation of antioxidant protective mechanisms. The purpose of this communication is to analyze the role of ROS in light signal transduction, mediated in Neurospora crassa cells by the White Collar Complex.     

Oxidative stress in childhood type 1 diabetes: Results from a study covering the first 20 years of evolution

This study aimed to further analyse the potential role of oxidative stress in children and adolescents with type 1 diabetes at clinical onset, during disease progression and when early microvascular complications ( + DC) appeared. Compared with age-matched controls, diabetic patients had greater oxidative damage to lipids, proteins and DNA demonstrated by analysis of plasma and erythrocyte malondialdehyde, carbonyl proteins and leukocyte 8-hydroxy-deoxyguanosine, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma lipid levels were significantly associated with lipid and protein oxidation products. Erythrocyte glutathione and glutathione-peroxidase activity were significantly decreased with the lowest values at onset and in + DC sub-groups. Insulin therapy in the first year improved metabolic and oxidant-antioxidant status and, consequently, hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation, thereby supporting the concept of glucotoxicity and lipotoxicity being inter-related. The overall increase in lipid, protein and DNA oxidative damage in diabetic patients with microangiopathy could be pathogenetically relevant in the early development of diabetes-related complications.     

Oxidative stress in childhood type 1 diabetes: Results from a study covering the first 20 years of evolution

This study aimed to further analyse the potential role of oxidative stress in children and adolescents with type 1 diabetes at clinical onset, during disease progression and when early microvascular complications ( + DC) appeared. Compared with age-matched controls, diabetic patients had greater oxidative damage to lipids, proteins and DNA demonstrated by analysis of plasma and erythrocyte malondialdehyde, carbonyl proteins and leukocyte 8-hydroxy-deoxyguanosine, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma lipid levels were significantly associated with lipid and protein oxidation products. Erythrocyte glutathione and glutathione-peroxidase activity were significantly decreased with the lowest values at onset and in + DC sub-groups. Insulin therapy in the first year improved metabolic and oxidant-antioxidant status and, consequently, hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation, thereby supporting the concept of glucotoxicity and lipotoxicity being inter-related. The overall increase in lipid, protein and DNA oxidative damage in diabetic patients with microangiopathy could be pathogenetically relevant in the early development of diabetes-related complications.     

Oxidative stress and diabetes in pregnant rats

A considerable amount of clinical and experimental evidence now exists suggesting the involvement of free radical-mediated oxidative processes in the pathogenesis of diabetic complications. If the diabetic state is associated with a generalized increase in oxidative stress, it might well be reflected in the alterations in embryonic and fetal development during pregnancy. In the present study, incidence of the malformed fetuses, biochemical parameters and antioxidant system activity of streptozotocin (STZ)-induced diabetic pregnant rats was investigated and the results obtained were compared with those of the control group (non-diabetic). Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. All the females were killed on Day 21 of pregnancy and the fetuses were analyzed. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic dams presented hyperglycemia, hyperlipemia, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased reduced glutathione (GSH), hepatic glycogen and superoxide dismutase (SOD) determinations. There was an increased incidence of skeletal and visceral malformation in fetuses from diabetic rats. Our findings suggest that oxidative stress occurs in the diabetic pregnant state, which might promote maternal homeostasis alterations. These diabetic complications might be a contributory factor to conceptus damage causing embryonic death (abortion/miscarriage) or the appearance of malformations in the fetuses of diabetic dams. Antioxidant treatment of women with diabetes may be important in future attempts to prevent congenital malformations.     

Oxidative stress sensitivity in Debaryomyces hansenii

Debaryomyces hansenii is an osmotolerant and halotolerant yeast of increasing interest for fundamental and applied research. In this work, we have performed a first study on the effect of oxidative stress on the performance of this yeast. We have used Saccharomyces cerevisiae as a well-known reference yeast. We show that D. hansenii is much more susceptible than S. cerevisiae to cadmium chloride, hydrogen peroxide or 1,4-dithiothreitol. These substances induced the formation of reactive oxygen species (ROS) in both yeasts, the amounts measured being significantly higher in the case of D. hansenii . We also show that NaCl exerted a protective effect against oxidative stress in Debaryomyces , but that this was not the case in Saccharomyces because sodium protected that yeast only when toxicity was induced with cadmium. On the basis of the present results, we raised the hypothesis that the sensitivity to oxidative stress in D. hansenii is related to the high amounts of ROS formed in that yeast and that observations such as low glutathione amounts, low basal superoxide dismutase and peroxidase activities, decrease in ATP levels produced in the presence of ROS inducers and high cadmium accumulation are determinants directly or indirectly involved in the sensitivity process.