Hypoxia increases plasma glutathione disulfide in rats

We tested the hypothesis that hypoxia causes cellular oxidative stress by measuring plasma concentrations of glutathione disulfide (GSSG) in rats exposed to acute and subacute hypoxia. In awake, unanesthetized, catheter-implanted rats, exposure to 8% O2 for 10 min caused pulmonary vasoconstriction and increased plasma GSSG. This increase in plasma GSSG was reversible upon re-exposure to room air. In another group of rats exposed to 48 hours of hypobaric hypoxia (Pb 450 mmHg, equivalent to about 14,500 feet altitude), plasma GSSG, but not total glutathione, was significantly increased over control values (2.83 +/- 0.24 vs 1.84 +/- 0.14 nmol/ml, p less than 0.05). While lung tissue GSSG in high altitude-exposed rats were somewhat higher than in controls (17.4 +/- 7.0 vs 11.9 +/- 3.6 nmol/g wet lung wt.), the difference was not statistically significant. Treatment of the rats with a radical scavenger, DMSO, before altitude exposure, blocked the increase in plasma GSSG (1.86 +/- 0.16 nmol/ml). We conclude that both acute and subacute hypoxia increase plasma GSSG in rats and speculate that hypoxia induces cellular oxidative stress in vivo.     

Increased chemosensitivity and elevated reactive oxygen species are mediated by glutathione reduction in glutamine deprived neuroblastoma cells

Purpose Glutamine is an essential amino acid for the synthesis of glutathione (GSH), the major endogenous antioxidant which protects cells from oxidative injury. To evaluate the effects of glutamine concentrations, cell growth, GSH levels, oxidative stress, and chemosensitivity were evaluated in neuroblastoma cell lines. Methods Three human neuroblastoma cell lines (SMS-KCNR, SMS-KANR, SMS-LHN) were cultured with different concentrations of glutamine (2, 0.2 and 0 mM) under hypoxic (5% O₂) or normoxic (20% O₂) condition. Cell proliferation and chemosensitivity were determined by MTT assay, and the levels of intracellular GSH were measured by DTNB-GSSG reductase method. Cellular reactive oxidative species (ROS) were quantified by flow cytometry. Results There was a significant decrease of cell growth in low glutamine (0.2 and 0 mM) compared with control (2 mM) in all three cell lines (P < 0.01), while adding GSH partially restored the reduced cell proliferation by low glutamine. The levels of GSH in neuroblastoma cells decreased significantly in low glutamine compared with the levels of control cells cultured in 2 mM glutamine (P < 0.05), and the accumulation of cellular ROS was significantly higher in 0 mM glutamine compared to the control. Moreover, glutamine deprivation significantly enhanced cytotoxicity of L-PAM in all three cell lines, which was abolished after addition of GSH. Conclusion Glutamine deprivation decreased cell proliferation and enhances cell chemosensitivity in neuroblastoma, which is presumably associated with GSH depletion.     

Effect of glutathione redox state on Leydig cell susceptibility to acute oxidative stress

The free radical, or oxidative stress, theory posits that imbalance in cells between prooxidants and antioxidants results in an altered redox state and, over time, an accumulation of oxidative damage. We hypothesized herein that cells with an increasingly prooxidant intracellular environment also might be particularly susceptible to acute oxidative stress. To test this hypothesis, MA-10 cells were used as a model because of their well-defined, measurable function, namely progesterone production. We first experimentally altered the redox environment of the cells by their incubation with buthionine sulfoximine (BSO) or diethyl maleate (DEM) so as to deplete glutathione (GSH), and then exposed the GSH-depleted cells acutely to the prooxidant tert-butyl hydroperoxide (t-BuOOH). Neither BSO nor DEM by themselves affected progesterone production. However, when the GSH-depleted cells subsequently were exposed acutely to t-BuOOH, intracellular reactive oxygen species concentration was significantly increased, and this was accompanied by significant reductions in progesterone production. In striking contrast, treatment of control cells with t-BuOOH had no effect. Depletion of GSH and subsequent treatment of the cells with t-BuOOH-induced the phosphorylation of each of ERK1/2, JNK and p38, members of the MAPK family. Inhibition of p38 phosphorylation largely prevented the t-BuOOH-induced down-regulation of progesterone production in GSH-depleted cells. These results suggest that, as hypothesized, alteration of the intracellular GSH redox environment results in the increased sensitivity of MA-10 cells to oxidative stress, and that this is mediated by activation of one or more redox-sensitive MAPK members.     

不同程度间歇低氧大鼠血清丙二醛含量、超氧化物歧化酶和谷胱甘肽过氧化物酶活性的变化

目的 通过测定不同程度间歇低氧大鼠血清丙二醛(MDA)含量及部分抗氧化酶的活性,以探讨氧化应激与阻塞性睡眠呼吸暂停模式间歇低氧的关系,为进一步研究阻塞性睡眠呼吸暂停综合征所致心血管并发症的发病机制提供研究基础.方法 160只成年雄性Wistar大鼠随机均分为5组:5%间歇低氧组、7.5%间歇低氧组、10%间歇低氧组、1...     

低氧大鼠肺内硝基酪氨酸的变化研究

目的 观察在低氧大鼠肺组织中氧化产物硝基酪氨酸(nitrotryrosine,NT)表达的变化,探讨氧化应激机制在低氧性肺动脉高压形成中的作用.方法 将14只雄性Wistar大鼠随机分为对照组、低氧组.以常压低氧3周制备肺动脉高压模型,测量各组大鼠平均肺动脉压(mean pulmonary arterial pressure,mPAP)和右心肥厚指数(right ventricle hypertrophy index,RVHI);图像技术测定管壁厚度占血管外径的百分比(wall thickness %,WT %)和管壁面积占总面积的百分比(wall area%,WA%);采用免疫组织化学法观察两组大鼠肺小动脉管壁NT的表达.结果 ①低氧组大鼠mPAP(22.84±1.79)mm Hg和RVHI(29.78±1.07)%与对照组mPAP(16.67±0.97)mm Hg和RVHI(24.22±0.48)%相比,差异有统计学意义(P均＜0.01).②低氧组WT%(24.96±3.70)%和WA%(73.31 ±6.51)%与对照组WT%(14.19±2.61)%和WA%(46.67±7.42)%相比,差异有统计学意义(P均＜0.01).③低氧组大鼠近端肺小动脉管壁的NT染色强度(1.52±0.07)与对照组(1.00±0.00)相比,差异有统计学意义(P＜0.01).两组大鼠远端肺小动脉管壁NT染色强度无明显变化(P＞0.05).低氧组大鼠近端肺小动脉管壁NT表达强度与mPAP值呈正相关(r=0.867,P＜0.05).结论 低氧可诱导大鼠mPAP增高及肺组织内NT产生增加,其作用机制可能与低氧诱导氧化应激有关.     

Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, exert various beneficial effects independent of serum cholesterol reduction; among others is antioxidative action. Human promyelocytic cells (HL-60) were used to examine the effect of the statin rosuvastatin on reactive oxygen species-induced DNA damage, formation of oxidative stress and expression of glutathione metabolising enzymes.Rosuvastatin from 10 nM significantly reduced DNA damage induced by phorbol 12-myristate 13-acetate (PMA) or by hydrogen peroxide, as assessed by the comet assay. PMA-provoked formation of reactive oxygen species, measured by flow cytometric measurement, was also prevented by rosuvastatin. Pre-incubation of cells with rosuvastatin revealed a protective effect of the statin even after its removal from the incubation medium. Total glutathione in cells treated with PMA, with and without co-incubation with rosuvastatin, was increased significantly in cells incubated with rosuvastatin alone. The quantification of the mRNA and activity of glutathione synthesizing enzymes by PCR showed a significant upregulation of γ-glutamylcysteine synthetase.In conclusion, rosuvastatin exerts antioxidative effects, which are also capable of preventing DNA damage. These effects seem to be independent of HMG-CoA reductase inhibition and involve the induction of the expression of antioxidant defense enzymes.     

Effect of age on alteration of glutathione metabolism following chronic cigarette smoke inhalation in mice

Cigarette smoke is the most common oxidant stress in daily life and may affect the antioxidant capacity in humans and animals. The antioxidant functions may play an important role in preventing age-related disorders. However, influences of chronic cigarette smoke on the antioxidant capacity of visceral organs have not been investigated in the age. Senescene-accelerated mice (SAM) are good models for studying physiologic and/or pathologic aging. A senescene-prone strain, SAMP2, shows characteristics of premature aging. The senescence-resistant strain, SAMR1, exhibits relatively normal aging. In this study we examined the effects of chronic cigarette smoke exposure on the glutathione (GSH) metabolism of visceral organs in the two strains of mice that were 6 and 18 months old. After a 4-week cigarette or air exposure, total GSH and oxidized GSH (GSSG) in the organs were examined. In the young (6-month-old) mice, exposure to cigarette smoke caused a significant decrease of GSH in liver, blood, and lung of SAMP2 but not in those of SAMR1. In the aged (18-month-old) mice reduced GSH with a marked increase of GSSG were found in liver of both strains of SAM following cigarette smoke exposure. The baseline values of GSH and the GSSG/GSH ratio after air exposure were slightly changed with age, and the values after exposure to cigarette smoke were changed markedly with advancing age. These results indicate that GSH metabolism may be impaired by chronic cigarette smoke exposure in mice and that aged mice are more susceptible to cigarette smoke than young mice.     

Mechanism of azathioprine-induced injury to hepatocytes: roles of glutathione depletion and mitochondrial injury

BACKGROUND/AIMS: We sought evidence that azathioprine causes cell death through reduced glutathione (GSH) depletion and mitochondrial injury. METHODS: Studies were conducted in primary cultures of rat hepatocytes and cultured Hep G2 cells. RESULTS: Azathioprine toxicity to rat hepatocytes was preceded by depletion of GSH. Prior GSH depletion (by treatment with buthionine sulfoximine) enhanced toxicity whilst supplemental GSH or N-acetylcysteine was protective. In hepatocytes, GSH is consumed during metabolism of azathioprine to 6-mercaptopurine. 6-Mercaptopurine was not toxic to hepatocytes, suggesting that the later steps in azathioprine metabolism were not related to the pathogenic mechanism. In Hep G2 cells, azathioprine did not alter levels of GSH and was not toxic. Ultrastructural studies showed hepatocyte mitochondrial lesions after exposure to azathioprine, but no features of apoptosis. Azathioprine produced rapid and profound depletion of adenosine 5'-triphosphate (ATP). Cyclosporin A and glycine afforded protection against azathioprine toxicity, and Trolox and high-dose allopurinol also attenuated injury. CONCLUSIONS: The mechanism of azathioprine toxicity to hepatocytes involves depletion of GSH leading to mitochondrial injury with profound depletion of ATP and cell death by necrosis. Cell death was prevented by potent antioxidants, glycine and blocking the mitochondrial permeability transition pore.     

Age-related alterations of plasma glutathione and oxidation of redox potentials in chimpanzee (Pan troglodytes) and rhesus monkey (Macaca mulatta)

Chimpanzee (Pan troglodytes) and rhesus macaque (Macaca mulatta) and humans (Homo sapiens) share physiological and genetic characteristics, but have remarkably different life spans, with chimpanzees living 50–60 % and the rhesus living 35–40 % of maximum human survival. Since oxidative processes are associated with aging and longevity, we might expect to see species differences in age-related oxidative processes. Blood and extracellular fluid contain two major thiol redox nodes, glutathione (GSH)/glutathione-disulfide (GSSG) and cysteine (Cys)/cystine (CySS), which are subject to reversible oxidation–reduction reactions and are maintained in a dynamic non-equilibrium state. Disruption of these thiol redox nodes leads to oxidation of their redox potentials (E_hGSSG and E_hCySS) which affects cellular physiology and is associated with aging and the development of chronic diseases in humans. The purpose of this study was to measure age-related changes in these redox thiols and their corresponding redox potentials (E_h) in chimpanzees and rhesus monkeys. Our results show similar age-related decreases in the concentration of plasma GSH and Total GSH as well as oxidation of the E_hGSSG in male and female chimpanzees. Female chimpanzees and female rhesus monkeys also were similar in several outcome measures. For example, similar age-related decreases in the concentration of plasma GSH and Total GSH, as well as age-related oxidation of the E_hGSSG were observed. The data collected from chimpanzees and rhesus monkeys corroborates previous reports on oxidative changes in humans and confirms their value as a comparative reference for primate aging.

Graphical abstract

Open in a separate windowGSH declined while the GSH/GSSG redox potential (EhGSSG) increased with age indicating age-related increased oxidative stress.     

Effect of DASH diet on oxidative stress parameters: A systematic review and meta-analysis of randomized clinical trials

Background and aimsOxidative stress (OS) is one of the main risk factors for several chronic diseases. The Dietary Approaches to Stop Hypertension (DASH) contain many antioxidants and may contribute to managing OS.ObjectiveTo perform a systematic review and meta-analysis to examine the impacts of the DASH diet on OS parameters.MethodsA comprehensive electronic search in MEDLINE, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials was performed through September 2020 to find related studies evaluating the impact of the DASH diet on OS parameters. Standardized mean differences were pooled using random-effects meta-analysis.ResultsEight studies with a total of 317 subjects met our inclusion criteria. Four studies included in meta-analysis model with 200 participants (100 in treatment and 100 in control group). The DASH diet was associated with a statistically significant decrease in malondialdehyde (MDA) (SMD: −0.53; 95% CI: −0.89, −0.16; I² = 42.1%), and a significant increase in glutathione (GSH) (SMD: 0.83; 95% CI: 0.36, 1.03; I² = 42.1%). Meta-analysis found no statistically significant effect of DASH diet on nitric oxide (NO) (SMD: −1.40; 95% CI: −0.12, 1.93; I² = 92.6%) or total antioxidant capacity (TAC) levels (SMD: 0.95; 95% CI: −0.10, 1.99; I² = 87.6%).ConclusionOur results demonstrated that a DASH diet could significantly increase GSH and decrease MDA levels. Furthermore, there is a trend to improve TAC, NO, and f2-isoprostanes by the adherence to the DASH diet. However, long-term, large sample size and well-designed randomized clinical trials are still needed to draw concrete conclusions about DASH diet’s effects on OS parameters.     

Maintaining good hearing: Calorie restriction,Sirt3, and glutathione

Reducing calorie intake extends the lifespan of a variety of experimental models and delays progression of age-related hearing loss (AHL). AHL is a common feature of aging and is characterized by age-related decline of hearing associated with loss of sensory hair cells, spiral ganglion neurons, and/or stria vascularis degeneration in the cochlea. Sirtuins are a family of NAD⁺-dependent enzymes that regulate lifespan in lower organisms and have emerged as broad regulators of cellular fate. Our recent study indicated that mitochondrial Sirt3, a member of the sirtuin family, mediates the anti-aging effects of calorie restriction (CR) on AHL in mice. Interestingly, we also found that weight loss alone may not be sufficient for maintaining normal hearing. How does CR slow the progression of AHL through regulation of Sirt3? Here we review the evidence that during CR, Sirt3 slows the progression of AHL by promoting the glutathione-mediated mitochondrial antioxidant defense system in mice. A significant reduction in food consumption in one's daily life may not be a desirable and realistic option for most people. Therefore, identification/discovery of compounds that induce the activation of SIRT3 or glutathione reductase, or that increase mitochondrial glutathione levels has potential for maintaining good hearing through mimicking the anti-aging effects of CR in human inner ear cells.     

N-乙酰半胱氨酸、还原型谷胱甘肽及地塞米松对人甲状腺细胞氧化应激的影响

取人甲状腺腺瘤旁正常甲状腺组织进行细胞培养,以1 000 IU/ml干扰素γ(IFN-γ)+10ng/ml肿瘤坏死因子α(TNF-α)、1 mmol/L N-乙酰半胱氨酸(NAC)、1 mmol/L还原型谷胱甘肽(GSH)、10μmol/L地塞米松(DEX)孵育,测定细胞培养上清液中丙二醛、谷胱甘肽过氧化物(GSH-Px)和总超氧化物歧化酶(SOD)水平.结果显示,IFN-y+TNF-α处理组与对照组比较,丙二醛水平显著增加(P＜0.05),GSH-Px和SOD活性显著下降(P＜0.05);经NAC、GSH和DEX干预后,IFN-γ+TNF-α刺激的丙二醛水平均显著下降(P＜0.05),GSH-Px和SOD活性显著升高(P＜0.05).这些结果表明IFN-γ和TNF-α可以诱导甲状腺细胞发生氧化应激,NAC、GSH及DEX可通过增加细胞GSH-Px、SOD活性和降低丙二醛含量来拮抗氧化应激反应.     

间歇低氧对大鼠交感神经兴奋性的影响及抗氧化剂的干预作用

目的 探究大鼠交感神经兴奋性在慢性间歇低氧(CIH)诱发高血压过程中的作用及交感神经兴奋性增强的机制与氧化应激的关系,观察抗氧化剂4-羟基-2,2,6,6-四甲基哌啶( Templ)对血压的干预作用.方法 48只雄性Wistar大鼠按随机数字表法分为6组,每组8只,分别为常氧对照组、间歇低氧空白对照组(低氧对照组)、Tempol预干预组(干预1组)、Tempol后干预组(干预2组)、生理盐水预对照组(对照1组)及后对照组(对照2组).除常氧对照组外均给予间歇低氧环境,其中干预1组和干预2组分别于实验前和实验后第28天给予10％ Tempol 100 mg·kg-1·d-1腹腔注射,对照1组和对照2组同时分别给予等量生理盐水腹腔注射.测定大鼠动脉收缩压、血清去甲肾上腺素、肾上腺素水平以及肾上腺组织匀浆中丙二醛水平.结果 6周后,低氧对照组收缩压与干预1组和干预2组相比,差异无统计学意义.干预1组收缩压[(114±6) mmHg,1 mm Hg=0.133 kPa]与常氧对照组和实验前相比无明显变化,其余各组大鼠收缩压均高于常氧对照组和实验前水平(F值为15.045,均P＜0.05).干预1组和干预2组收缩压[(128 ±6)mm Hg]均低于对照1组[( 138±10)mm Hg]和对照2组[(138±10)mm Hg,均P＜0.05],但干预2组高于干预1组(P＜0.01).常氧对照组收缩压水平与实验前比较差异无统计学意义.低氧对照组与对照1组和对照2组相比,血清去甲肾上腺素、肾上腺素及肾上腺匀浆中丙二醛水平均无统计学意义.干预1组和干预2组去甲肾上腺素、肾上腺素及丙二醛水平均低于对照1组和对照2组(P＜0.05),但干预2组各指标仍高于常氧对照组(P＜0.05)及干预1组(P＜0.05或P＜0.01).干预1组去甲肾上腺素、肾上腺素及丙二醛水平与常氧对照组比较无明显差异.结论 CIH可能导致交感神经活性增强,其途径可能为通过氧化应激产生活性氧,可能是CIH引起高血压的重要机制.抗氧化剂干预可能对防治OSAS合并症高血压发生起到一定作用.     

慢性间歇低氧对大鼠肝脏的损伤及4-羟基-2,2,6,6-四甲基哌啶的干预作用

目的 探讨慢性间歇低氧(CIH)对大鼠肝脏损伤机制和4-羟基-2,2,6,6-四甲基哌啶( tempol)的干预作用及其可能机制.方法 应用CIH大鼠模型,模拟OSAS慢性间歇低氧/再氧和病理生理过程.32只雄性Wistar大鼠采用随机数字表法分为低氧对照组、低氧干预组、低氧盐水组和常氧对照组,共4组,每组8只.CIH各组最低氧浓度均为5％,低氧频率均为30次/h,8 h/d.暴露6周后处死大鼠,取肝脏组织行石蜡切片HE染色观察肝细胞形态变化,酶联免疫吸附法(ELISA)测定大鼠肝脏中核因子-κB、谷胱甘肽过氧化物转移酶(GSH-PX)和丙二醛的水平.结果 肝脏病理检查可见低氧对照组及低氧盐水组肝细胞胞膜破坏,细胞水肿,胞质稀疏,核深染;低氧干预组、常氧对照组未见明显肝脏损害.与常氧对照组比较:低氧对照组和低氧盐水组核因子-κB[(12.4±2.0) ng/g,(12.2±1.9) ng/g]和丙二醛[(101±22)μmol/g,(99±18) μmol/g]水平均升高(均P＜0.05),GSH-PX活性[(88±17) U/mg,(90+15) U/mg]均下降(均P＜0.05);与低氧对照组、低氧盐水组比较,低氧干预组核因子-κB[(7.8 +1.3) ng/g]和丙二醛[(59±10) μmol/g]水平均下降(均P＜0.05),GSH-PX活性[(181±29) U/mg]均升高(均P＜0.05);低氧干预组与常氧对照组比较,GSH-PX和丙二醛水平差异均无统计学意义(均P＞0.05),但核因子-κB水平高于常氧对照组[(4.1±0.9) ng/g,P＜0.05];低氧对照组与低氧盐水组比较以上指标差异均无统计学意义(均P＞0.05).核因子-κB水平与GSH-PX活性和丙二醛水平分别呈负相关(r=-0.0754,P＜0.01)和正相关(r =0.689,P＜0.01)关系.结论 CIH可通过氧化应激和激活前炎性转录因子核因子-κB造成肝脏损伤;tempol可通过抗氧化作用清除活性氧干预CIH肝脏损害的发生.     

Oxidative stress and thyroid hormones in patients with liver diseases

BackgroundThe liver metabolizes the thyroid hormones and regulates their systemic endocrine effects so liver disease could affect thyroid hormone metabolism. Oxidative stress could play a role in the pathogenesis and progression of liver diseases. The objective of this study was to investigate serum levels of oxidative stress and antioxidant in liver diseases as prognostic markers and know the importance of these antioxidants level in relation to thyroid hormones.MethodsSerum nitric oxide (NO), malondialdehyde (MDA) and triiodothyronine (T₃), thyroxine (T₄), thyroid stimulating hormone (TSH), apolipoprotein-1 (APOA1) levels and erythrocyte reduced glutathione (GSH) level and glutathione peroxidase (GSHPx) and glutathione reductase (GR) activities were determined in 20 control subjects, 13 patients with non-alcoholic steatohepatitis (NASH), 18 patients with chronic HCV, 17 patients with compensated cirrhotic HCV and 42 patients with decompensated cirrhotic HCV.ResultsCirrhotic patients with HCV had higher NO and MDA levels while lower T₃ and erythrocyte GSH levels, and GSHPx activity than the chronic. Serum T₃ showed negative correlation with serum NO and MDA whereas positive correlation with APOA1, GSH, and GSHPx in cirrhotic patients with HCV.ConclusionThe measurement of the total T₃, NO, MDA, GSH reduced and GSHPx as biomarkers for liver diseases might be a beneficial tool, helping in monitoring the state of liver disease patients.     

还原型谷胱甘肽对糖尿病大鼠肾脏保护作用的机制研究

目的 探讨还原型谷胱甘肽(reduced glutathione,GSH)对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠肾脏线粒体保护及机制.方法 STZ诱导糖尿病大鼠模型,将糖尿病大鼠随机分为糖尿病非干预组(DM组)和GSH干预组(DM+GSH组),并以正常组(NC组)作对照.干预8周后,测定各组大鼠尿白蛋白排泄率(UAER)、血肌酐(SCr)、血尿素氮(BUN)水平,光镜观察肾脏组织形态学变化,检测血清和肾皮质中丙二醛(MDA)、超氧化物歧化酶(SOD)的含量以及各组肾脏线粒体膜电位和肿胀度的变化.结果 DM组大鼠UAER、SCr、BUN较NC组显著升高(均P＜0.05),肾脏组织发生糖尿病肾病病理改变,血清MDA(μmol/L)和肾皮质中MDA(μmol/g)显著升高(5.59±1.03 vs 2.97±0.77;4.80±0.83 vs 2.98±0.75;均P＜0.01),血清SOD(U/ml)和肾皮质中SOD(U/mg)含量显著降低(89.13±22.73 vs 124.1±9.27;46.05±10.24 vs 89.89±17.62;均P＜0.01),肾脏线粒体膜电位明显降低(495.79±124.71 vs 965.77±246.48,P＜0.05),线粒体肿胀度趋势明显减弱.与DM组相比,DM+GSH组大鼠UAER、SCr、BUN显著降低(均P＜0.05),肾脏病理形态得到一定改善.血清MDA(μmol/L)和肾皮质中MDA(μmol/g)降低(4.15±0.59 vs 5.59±1.03;3.39±0.61 vs 4.80±0.83;均P＜0.05),血清SOD(U/ml)及肾皮质中SOD(U/mg)升高(112.92±8.93 vs 89.13±22.73;83.15±16.75 vs 46.05±10.24;均P＜0.05),肾脏线粒体膜电位显著升高(715.97±188.65 vs 495.79±124.71,P＜0.05),线粒体肿胀度趋势增强.结论 还原型谷胱甘肽对STZ诱导的糖尿病大鼠肾脏病变有一定程度的保护作用,其机制可能与线粒体的功能改变有一定关系.     

阻塞性睡眠呼吸暂停低通气综合征及其相关高血压患者血清过氧化氢酶、谷胱甘肽过氧化物酶和丙二醛水平的变化

目的 探讨阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)及阻塞性睡眠呼吸暂停低通气综合征相关高血压(obstructive sleep apnea-hypopnea associated hypertension,OSAHAHT)患者血清过氧化氢酶(catalase,CAT)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)和丙二醛(malonaldehyde,MDA)水平的变化.方法 选择OSAHS患者24例,OSAHAHT患者21例;正常对照组23名,测定血清CAT、GSH-PX、MDA水平.并与睡眠呼吸监测指标进行相关分析.结果 与正常对照组比较,OSAHS组及OSAHAHT组血清CAT、GSH-PX活性均降低(P<0.01),MDA浓度均升高(P<0.01).OSAHS及OSAHAHT患者血清CAT、GSH-PX、MDA水平与反映睡眠呼吸暂停严重程度的指标有相关性(P<0.01).结论 OSAHS患者存在CAT、GSH-PX、MDA水平的变化,且与OSAHS的病情严重程度相关;氧化应激及氧化损伤在OSAHAHT患者中更明显.