Changing face of hepatic encephalopathy: Role of inflammation and oxidative stress

The face of hepatic encephalopathy(HE) is changing.This review explores how this neurocognitive disorder,which is associated with both acute and chronic liver injury,has grown to become a dynamic syndrome that spans a spectrum of neuropsychological impairment,from normal performance to coma.The central role of ammonia in the pathogenesis of HE remains incontrovertible.However,over the past 10 years,the HE community has begun to characterise the key roles of inflammation,infection,and oxidative/nitrosative s...     

Diabetes and dyslipidaemia are associated with oxidative stress independently of inflammation in long-term antiretroviral-treated HIV-infected patients

AimAgeing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities.MethodsIncluded were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997–1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, β2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses.ResultsAt the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45–56); BMI was 23.0 kg/m² (21.1–25.4), CD4+ lymphocytes were 620 cells/mm³ (453–790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events.ConclusionIn long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.     

Heme oxygenase attenuates oxidative stress and inflammation, and increases VEGF expression in portal hypertensive rats

BACKGROUND/AIMS: The pathophysiological significance of heme oxygenase-1 up-regulation in portal hypertension is not completely understood. In this study, we determined the role of heme oxygenase-1 on oxidative stress, inflammation, angiogenesis, and splanchnic hemodynamics in rats with portal hypertension induced by partial portal vein ligation. METHODS: Rats were treated with the heme oxygenase inhibitor SnMP or vehicle for 7 days. Then, oxidative stress was quantified by superoxide anion production, and inflammatory response was assessed by immunofluorescence. Expression of angiogenesis mediators was determined by western blotting, and the extent of portosystemic collaterals by radioactive microspheres. Hemodynamic studies were performed by flowmetry. RESULTS: Oxidative stress was significantly increased in the mesentery of portal hypertensive rats, as compared with sham-operated controls. In portal hypertensive rats, chronic heme oxygenase inhibition (1) potentiated oxidative stress and inflammation, (2) significantly decreased VEGF expression, without modifying the extent of collaterals or the splanchnic neovascularization, and (3) significantly decreased superior mesenteric artery blood flow and portal pressure. CONCLUSIONS: This study demonstrates that heme oxygenase plays an important (beneficial) role attenuating oxidative stress and inflammation, but it also plays a detrimental role in stimulating VEGF production, and contributing to the development of hyperdynamic splanchnic circulation in rats with portal hypertension.     

Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients

Aim/hypothesis Evidence suggests that postprandial hyperglycaemia may be a cardiovascular risk factor in diabetes. Oxidative stress and inflammation are involved in the pathogenesis of diabetic complications and previous studies have shown increased oxidative stress and inflammation in the postprandial phase in diabetic patients. The aim of the present study was to evaluate whether controlling postprandial hyperglycaemia with S21403 (mitiglinide) is accompanied by a reduced generation of oxidative stress and inflammation.Subjects and methods Forty type 2 diabetic patients participated in the study. Two different breakfast-tests were performed in each patient, with placebo or S21403. Plasma nitrotyrosine, plasma malondialdehyde (MDA), oxidised LDL (oxLDL), plasma total radical-trapping antioxidant parameter (TRAP), IL-6, IL-18, TNF-, plasma glucose and insulin were measured.Results After the administration of S21403, 40 mg, a rapid stimulation of insulin secretion was observed, accompanied by a reduction of postprandial hyperglycaemia. With S21403, a significant decrease of either nitrotyrosine, MDA and oxLDL levels, and a preservation of plasma TRAP compared with placebo was found. Significant decreases of IL-6, IL-18 and TNF- were also observed with S21403 compared with placebo.Conclusions/interpretation This study shows that controlling postprandial hyperglycaemia with S21403 significantly improves the cluster of oxidative stress and inflammation markers that are increased in the postprandial state in diabetic patients.     

The effect of increased dietary fruit and vegetable consumption on endothelial activation, inflammation and oxidative stress in hypertensive volunteers

Background and aims

Public health campaigns recommend increased fruit and vegetable (FV) consumption as an effective means of cardiovascular risk reduction. During an 8 week randomised control trial among hypertensive volunteers, we noted significant improvements in endothelium-dependent vasodilatation with increasing FV consumption. Circulating indices of inflammation, endothelial activation and insulin resistance are often employed as alternative surrogates for systemic arterial health. The responses of several such biomarkers to our previously described FV intervention are reported here.

Methods and results

Hypertensive volunteers were recruited from medical outpatient clinics. After a common 4 week run-in period during which FV consumption was limited to 1 portion per day, participants were randomised to 1, 3 or 6 portions daily for 8 weeks. Venous blood samples for biomarker analyses were collected during the pre and post-intervention vascular assessments. A total of 117 volunteers completed the 12 week study. Intervention-related changes in circulating levels of high sensitivity C-reactive protein (hsCRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) did not differ significantly between FV groups. Similarly, there were no significant between group differences of change in homeostasis model assessment (HOMA) scores.

Conclusions

Despite mediating a significant improvement in acetylcholine induced vasodilatation, increased FV consumption did not affect a calculated measure of insulin resistance or concentrations of the circulating biomarkers measured during this study. Functional indices of arterial health such as endothelium-dependent vasomotion are likely to provide more informative cardiovascular end-points during short-term dietary intervention trials.     

不同腹膜转运特性的腹膜透析患者炎症和氧化应激状态的研究

目的研究维持性腹膜透析(PD)患者腹膜转运特性对炎症和氧化应激状态的影响。方法选取2005年1月至12月四川大学华西医院肾内科门诊和住院的36例行腹膜透析的尿毒症患者,根据腹膜平衡试验分为高转运和高平均转运组(HPD)18例,低转运和低平均转运组(LPD)18例,选取同期未透析尿毒症患者18例及正常对照11例以分光光度法及免疫比浊法测定患者血清超氧化物歧化酶(SOD)、维生素E、维生素C、丙二醛(MDA)、C-反应蛋白(CRP)。结果非透析尿毒症患者血中维生素C、维生素E及SOD均低于维持性腹膜透析患者(P<0.05),CRP和MDA高于维持性腹膜透析患者(P<0.05);HPD组维生素C及SOD低于LPD组(P<0.05),MDA及CRP高于LPD组(P<0.05)。结论腹膜透析患者体内反映氧化应激状态和炎症状态的因子表达较非透析尿毒症者高;不同腹膜转运特性对尿毒症患者的氧化应激状态和炎症状态有不同的影响;较高转运特性者的氧化应激状态和炎症状态高于较低转运特性者。     

慢性炎症和氧化应激对老年2型糖尿病患者骨骼肌量和肌力的影响

目的:分析老年2型糖尿病患者骨骼肌质量和力量水平,探讨慢性炎症及氧化应激水平对其影响。方法:横断面病例对照研究,入选京西医院120例60岁及以上老年2型糖尿病(糖尿病组)患者和126例老年非糖尿病(非糖尿病组)患者,分别测定其骨骼肌质量、力量及血清慢性炎症因子白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)及氧...     

褪黑素对大气细颗粒物（PM 2.5）暴露大鼠肺部炎症反应和氧化应激的影响及其机制研究

目的：探讨褪黑素对大气细颗粒物(PM 2.5)暴露大鼠肺部炎症反应和氧化应激的影响及其机制。方法将48只清洁级 SD 大鼠随机(随机数字法)分成4组：空白对照组、NS 对照组、PM 2.5组及褪黑素(melatonin,MT)组,每组各12只。通过气管向肺内注入 PM 2.5悬液构建大鼠肺组织PM 2.5染毒模型,并通过灌胃溶液,采用肺组织 HE 染色、酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)及蛋白印迹等方法分别检测肺组织病理改变,如 TNF-α、IL-6、IL-1、MPO、SOD、MDA 以及 NF-κB p65蛋白表达。结果①与空白对照组及 NS 对照组比较,PM 2.5组大鼠肺组织出现明显损伤改变,MT 组大鼠肺组织损伤较 PM 2.5组明显减轻;②PM 2.5组大鼠肺组织 TNF-α、IL-6、IL-1表达明显增加(P <0.05),MT 组较 PM 2.5组 TNF-α、IL-6、IL-1表达明显下降(P <0.05);③PM 2.5组大鼠肺组织 SOD 表达较空白对照组及 NS 对照组明显下降(P <0.05),而 MPO 及 MDA 表达明显增加(P <0.05),而与 PM 2.5组比较,MT 组大鼠肺组织 SOD 表达增加,MPO 及 MDA 表达下降(P <0.05);④PM 2.5组 p65蛋白表达明显上调(P <0.05),而MT 组较 PM 2.5组 p65蛋白表达明显下降(P <0.05)。结论 PM 2.5能通过介导肺组织炎性反应及氧化应激导致肺组织损伤,且与活化 NF-κB 相关,MT 能显著抑制 PM 2.5所致 NF-κB 活化,减轻炎性反应及氧化应激,改善PM 2.5暴露大鼠肺损伤。     

中性粒细胞凋亡延迟与重叠综合征患者的氧化应激和系统性炎症

呼吸重叠综合征简称重叠综合征（OS）通常是指阻塞性睡眠呼吸暂停（OSA）和COPD的共患,其较单纯COPD或OSA存在更明显的低氧血症的发生,并且心血管并发症的发生率和病死率也明显增加。本文综述了OS导致氧化应激和系统性炎症的可能机制以及中性粒细胞凋亡延迟相关的调节机制。     

8-Hydroxydeoxyguanosine: not mere biomarker for oxidative stress, but remedy for oxidative stress-implicated gastrointestinal diseases

Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine (8-OHdG),which can bind to thymidine rather than cytosine,based on which,the level of 8-OHdG is gen-erally regarded as a biomarker of mutagenesis conse-quent to oxidative stress.For example,higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer.However,we have found that exogenous 8-OHdG can paradoxically reduce ROS production,attenuate thenuclear factor-κB signaling pathway,and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1,IL-6,cyclo-oxygenase-2,and induc-ible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1,NOX organizer-1 and NOX activator-1 in vari-ous conditions of inflammation-based gastrointestinal (GI) diseases including gastritis,inflammatory bowel disease,pancreatitis,and even colitis-associated carci-nogenesis.Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases,as well as the pre-vention of inflammation-associated GI cancer.In this editorial review,the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.     

Muscle wasting in rheumatoid arthritis:The role of oxidative stress

Rheumatoid arthritis(RA), the commonest inflammatory arthritis, is a debilitating disease leading to functional and social disability. In addition to the joints, RA affects several other tissues of the body including the muscle. RA patients have significantly less muscle mass compared to the general population. Several theories have been proposed to explain this. High grade inflammation, a central component in the pathophysiology of the disease, has long been proposed as the key driver of muscle wasting. More recent findings however, indicate that inflammation on its own cannot fully explain the high prevalence of muscle wasting in RA. Thus, thecontribution of other potential confounders, such as nutrition and physical activity, has also been studied. Results indicate that they play a significant role in muscle wasting in RA, but again neither of these factors seems to be able to fully explain the condition. Oxidative stress is one of the major mechanisms thought to contribute to the development and progression of RA but its potential contribution to muscle wasting in these patients has received limited attention. Oxidative stress has been shown to promote muscle wasting in healthy populations and people with several chronic conditions. Moreover, all of the aforementioned potential contributors to muscle wasting in RA(i.e., inflammation, nutrition, and physical activity) may promote pro- or antioxidative mechanisms. This review aims to highlight the importance of oxidative stress as a driving mechanism for muscle wasting in RA and discusses potential interventions that may promote muscle regeneration via reduction in oxidative stress.     

氟中毒与氧化应激

复习了氟中毒与氧化应激关系的有关文献。从近年来多数研究资料来看,氟中毒的一定阶段确可发生自由基增高和氧化应激反应,但要确定氧化应激与氟化物所致各种损害之间的因果联系,则还有许多工作要做。     

慢性肾衰竭患者高同型半胱氨酸血症、氧化应激和微炎症反应间的关系及其在动脉粥样硬化中的作用

目的　探讨同型半胱氨酸 (Hcy)血症和氧化应激、微炎症反应之间的关系 ,及其在慢性肾衰竭 (CRF)患者动脉粥样硬化 (AS)形成中的作用。方法　测 114例CRF患者 (CRF组 ,其中 6 2例行血液透析 ,非透析治疗 5 2例 )和 37例健康对照者 (健康对照组 )血浆总Hcy(tHcy)水平、循环丙二醛 (MDA)、谷胱苷肽过氧化物酶活性 (GSHPx)及血清C 反应蛋白 (CRP)、白细胞介素 (IL) 6、肿瘤坏死因子 (TNF)α水平 ,高分辨超声技术测颈动脉内膜 中层厚度 (IMT)及粥样硬化斑块。结果　非透析CRF患者血浆tHcy、MDA、CRP和TNFα水平高于健康对照组 ,且随肾功能损害程度的加重而升高 ,GSHPx则低于健康对照组 ;血液透析患者tHcy、MDA、CRP、IL 6和TNFα水平均高于非透析患者 ,GSHPx进一步降低。CRF患者IMT增厚阳性率、平均IMT及颈动脉粥样斑块检出率明显高于健康对照组。动脉病变越重 ,血浆tHcy、MDA及CRP水平越高 ,GSHPx越低。多因素逐步回归分析显示 ,tHcy、MDA、CRP、血糖和极低密度脂蛋白水平是影响颈总动脉IMT的危险因素 (R2 =0 5 72 ,P<0 0 0 1) ,影响CRF患者血浆MDA水平的因素有血浆GSHPx、tHcy、血肌酐 ,影响CRF患者血清CRP水平的因素有血清IL 6、TNFα、MDA、血浆白蛋白。结论　Hcy血症可能参与了CRF患者氧化应激的发生     

Infusion of lin−/sca-1+ and endothelial progenitor cells improves proinflammatory and oxidative stress markers in atherosclerotic mice

Background

The effects of direct infusion or indirect mobilization of progenitor cells on atherosclerotic plaque development and progression are not clear. We sought to investigate the effects of hematopoietic progenitors lineage negative/stem cell antigen-1 positive (lin−/sca-1+) cells, endothelial progenitor cells and G-CSF administration on the inflammatory and oxidative component of atherosclerosis.

Methods

Splenectomized ApoE^−/− C57BL/6 J mice (6–8 weeks of age) fed with a high-fat, cholesterol-rich diet for 6 weeks, were divided in four groups (n = 10/group) and received two intravenous injections of 5 × 10⁵ cells (lin−/sca-1+ or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 μg/kg/day) for 7 days or normal saline. sVCAM-1 (Vascular cell adhesion protein 1), sICAM-1 (soluble intercellular adhesion molecule-1), sE-Selectin, Metalloproteinase 9 (MMP-9), Plasminogen activator inhibitor (PAI-1), Interleukin 6 (IL-6), oxidized LDL (ox-LDL) levels and lipid PEROX were evaluated at the day of the first infusion, 7 days later and 6 weeks post-treatment with ELISA.

Results

The administration of both G-CSF and progenitor cells significantly decreased the levels of sICAM-1, sVCAM-1,sE-Selectin, IL-6, ox-LDL and lipid Perox 6 weeks after the initiation of treatment. No significant effects of lin−/sca-1+ cells, EPCs and G-CSF on PAI-1 and MMP-9 levels were observed. The effects of all treatments on the levels of pro-inflammatory molecules and oxidative stress parameters 7 days post-treatment were not significant. Interestingly, the levels of sICAM-1and sE-selectin were increased 7 days post-treatment.

Conclusions

Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells significantly decreased the levels of proinflammatory molecules and oxidative stress parameters in a murine model of atherosclerosis. The principal novelty of this work is that treatment with hematopoietic progenitors, EPCs or G-CSF may exert beneficial effects on vascular inflammation and atherosclerotic plaque development.     

瑞舒伐他汀联合普罗布考对大鼠动脉粥样硬化炎症与氧化应激的干预效果

目的观察瑞舒伐他汀联合普罗布考对大鼠动脉粥样硬化炎症及氧化应激相关指标的干预效果。方法雄性Wistar大鼠54只随机分5组,正常组(A组,n=12)、模型组(B组,n=12)、瑞舒伐他汀组(C组,n=10)、普罗布考组(D组,n=10)、瑞舒伐他汀加普罗布考组(E组,n=10)。A组普通饲料喂养,B组及药物干预组高脂饲料喂养同时给予卵清白蛋白(2.5 mg/kg)腹腔注射(5次/周)。从第9周开始,C、D、E组给予药物干预,C组给予瑞舒伐他汀5 mg/kg.d灌胃,D组给予普罗布考500 mg/kg.d灌胃,E组给予瑞舒伐他汀5 mg/kg.d+普罗布考500 mg/kg.d灌胃,A、B组给予生理盐水灌胃作为对照,连续干预8周。第16周末,所有大鼠称重,麻醉,开胸经右心房取血,留取血清。随后用ELISA法检测血清炎症指标血管内皮细胞钙黏蛋白(VE-cadherin)、脂联素(APN)及氧化应激指标8-异前列腺素-F2a(8-iso-PGF2a)、超氧化物歧化酶(SOD)表达水平。同时留取主动脉,进行HE染色,观察主动脉病理组织学变化。结果与正常组比较,模型组和药物干预组血清VE-cadherin、8-iso-PGF2a水平显著升高(P0.01),APN、SOD水平显著降低(P0.01),血管内膜增厚(P0.05),内皮细胞排列紊乱,可见泡沫细胞和单核细胞,且细胞间隙增宽。与B组比较,C、D、E组血清VE-cadherin、8-iso-PGF2a水平明显降低(P0.01),APN、SOD表达升高(P0.05),血管壁内膜厚度变薄(P0.01)。与C组比较,D、E组血清8-iso-PGF2a水平下降(P0.01),SOD水平升高(P0.01);与C组比较,E组血清VE-cadherin降低(P0.01),APN升高(P0.01)。与D组比较,E组血清VE-cadherin降低(P0.05),APN升高(P0.05);与C、D组比较,E组血管内膜变薄(P0.05)。结论瑞舒伐他汀与普罗布考均具有抗炎和抗氧化作用,普罗布考的抗氧化作用优于瑞舒伐他汀,两药联合应用可明显降低血清VE-cadherin的表达,并提高APN的表达,减轻主动脉血管内膜的损伤,改善动脉粥样硬化。     

Antioxidant intake, oxidative stress and inflammation among immigrant women from the Middle East living in Sweden: associations with cardiovascular risk factors

Background and aimsImmigrant women from the Middle East have higher cardiovascular risk compared to native women. Whether low antioxidant intake, oxidative stress or inflammation contributes to risk is unknown. In a cross-sectional study of 157 randomly selected foreign-born women (Iranian and Turkish) and native women living in Sweden, we investigated antioxidant status, oxidative stress (F₂-isoprostanes) and systemic inflammation (plasma high sensitive C-reactive protein; CRP) markers. We also investigated relationships between F₂-isoprostanes, CRP and cardiovascular risk factors.Methods and resultDietary intake was assessed using 24-h dietary recalls repeated four times. Micronutrient intake was not consistently different between groups. Serum α-tocopherol, but not γ-tocopherol levels, was lower in Turkish vs. Swedish women (P < 0.05). Turkish women had the highest F₂-isoprostane levels (P < 0.05 vs. Iranian women) and CRP levels (P < 0.01 vs. Swedish women and P = 0.05 vs. Iranian women). In immigrants (n = 97), F₂-isoprostanes correlated positively to insulin levels (r = 0.31, P < 0.01), and CRP was correlated to obesity and several cardiovascular risk factors (r-values >0.21, P values <0.05).ConclusionThe role of antioxidant status is unclear, whereas signs of oxidative stress and inflammation are evident in immigrant women from Middle East, especially Turkish women. Oxidative stress and low-grade inflammation might contribute to the higher cardiovascular risk previously observed in immigrant women. Further larger studies adjusting for more potential confounders are motivated to confirm these results.     

Potential anti-inflammatory action of resveratrol and piperine in adjuvant-induced arthritis: Effect on pro-inflammatory cytokines and oxidative stress biomarkers

Aim of the workResveratrol (RSV) is a phytoalexin with potent anti-inflammatory and anti-oxidant properties; however, its low bioavailability is considered a major obstacle. Piperine (PIP), an alkaloid, has been widely used as an effective bio-enhancer with drugs associated with low bioavailability. The current study was directed to examine the role of PIP in enhancing the efficacy of RSV in adjuvant-induced arthritis (AIA) in rats.Materials and methodsCarrageenan-induced paw edema model was designed for RSV and PIP doses optimization. Afterward, in the AIA model, rats were immunized at day 0 by sub-plantar injection of Freund’s complete-adjuvant. RSV (50 mg/kg) and PIP (20 mg/kg) were orally administered concurrently once daily from day 14 for two weeks. A standard anti-inflammatory drug, diclofenac, was employed for treatment validation. The paw volume was measured every 4 days. On day 29, rats were sacrificed and serum tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), thiobarbituric acid reactive substances (TBARS) and total nitrate/nitrite (NO_x) were estimated. Ankles were dissected for histopathological examinations and immuno-histochemical expression of nuclear factor-kappa B p65 (NF-κB p65).ResultsCo-administration of RSV and PIP significantly decreased the paw swelling and ameliorated the histopathological changes. In addition, the combined treatment highly reduced the serum TNF-α, IL-1β, TBARS and NO_x. Besides, a nearly negative expression of NF-κB p65 in the synovial tissue was observed by co-administration of PIP with RSV. Results of the combination treatment were comparable to that of the diclofenac treatment.ConclusionCo-administration of PIP enhanced the anti-inflammatory efficacy of RSV in the arthritic-induced rats.     

全反式维甲酸对高血压大鼠心脏氧化应激水平的影响

目的:探讨全反式维甲酸(atRA)对高血压心脏还原型辅酶I氧化酶P22亚单位(p22phox)表达以及氧化应激水平的影响。方法:采用12周龄雄性自发性高血压大鼠(SHR)及其同源对照WKY大鼠,经腹腔注射at-RA,为期1月。分别采用免疫印迹、硫代巴比妥酸比色以及透射电镜技术测定atRA治疗后SHR心脏p22phox的表达、丙二醛(MDA)含量以及心肌超微结构情况。结果:与WKY对照组相比,SHR心脏组织中p22phox蛋白表达与MDA含量明显升高(P均<0.01)。而atRA治疗后SHR(低、高剂量atRA组)大鼠心脏组织中p22phox蛋白表达与MDA水平出现下调(P均<0.05),同时伴有心肌损伤减轻。结论:长期atRA治疗可降低SHR大鼠心脏组织中p22phox表达与MDA水平,提示atRA在高血压病中具有一定的抗氧化效应。     

Potential ergogenic effects of L-arginine against oxidative and inflammatory stress induced by acute exercise in aging rats

In this study, we report protective effects of dietary L-arginine (L-Arg) supplementation against oxidative stress and inflammation in aging rats during exhaustive exercise. Thirty 18-month-old male Sprague-Dawley rats were randomly divided into four groups: sedentary control (SC); sedentary control with L-Arg treatment (SC+Arg); exhaustive exercise (E); and exhaustive exercise with L-Arg treatment (E+Arg). Rats in groups SC+Arg and E+Arg received a 2% L-Arg diet. Rats in groups E and E+Arg performed an exhaustive running test on a treadmill. The mean duration of exercise differed significantly between groups E and E+Arg (51+/-6 versus 63+/-3min). Results showed significant increases in xanthine oxidase (XO) and myeloperoxidase (MPO) activities and in lipid peroxidation end-product (malondialdehyde, MDA) levels of myocardial, muscular, hepatic, pulmonary, and renal tissues of exercised rats compared with SC and SC+Arg rats. The increased XO and MPO activities and MDA levels significantly decreased in exercised rats that were fed a diet supplemented with L-Arg. We also found that L-Arg supplementation prevented exhaustive exercise-induced elevations of plasma aminotransferase activity, and lactate and uric acid levels in aging rats. These findings suggest that L-Arg supplementation enhances exercise capacity and protects against oxidative damage and inflammatory responses caused by exhaustive exercise in aging rats.