Beneficial effects of a moderate consumption of red wine on cellular cholesterol efflux in young men

BACKGROUND AND AIM: Protection against coronary artery disease (CAD) by moderate alcohol consumption is thought to be partly mediated through an increase in high density lipoprotein (HDL) levels. The protective effect of HDL can be related to its role in reverse cholesterol transport. Some studies have shown that wine intake is associated with a lower CAD risk compared to other alcoholic beverages. METHODS AND RESULTS: In order to separate the possible beneficial effects of the alcoholic and the non-alcoholic components of red wine, three beverages were compared in a group of 56 healthy young men: red wine (W) (30 g alcohol/day), a solution with the same degree of alcohol (A) and alcohol-free red wine (AFW). Beverages were consumed in random order over a period of 14 days. W significantly increased serum HDL-C, Apo A-I, HDL3-C, LpA-I and LpA-I:A-II particles. With A, only ApoA-I, HDL3-C, LpA-I:A-II were increased, though triglycerides were also increased. AFW had no effect apart from decreasing HDL-C. Plasma CETP was never altered. Serum-promoted cellular cholesterol efflux was measured on 3H labelled Fu5AH cells. Fractional cholesterol efflux was increased only after W intake, by 7%. Efflux variations correlated positively with HDL-C, HDL3-C and HDL-phospholipid variations. CONCLUSIONS: A modest, specific beneficial effect of moderate red wine consumption was demonstrated in comparison to an alcoholic solution. This was due to its effects on lipoproteins and its stimulation of serum ability to induce efflux of cellular cholesterol.     

Comparison of acute effects of red wine, beer and vodka against hyperoxia-induced oxidative stress and increase in arterial stiffness in healthy humans

Objective

We determined and compared acute effects of different alcoholic beverages on oxygen-induced increase in oxidative stress plasma marker and arterial stiffness in healthy humans.

Methods

Ten males randomly consumed one of four tested beverages: red wine (RW), vodka, beer (0.32 g ethanol/kg body wt) and water as control. Every beverage was consumed once, a week apart, in a cross-over design. The volunteers breathed 100% normobaric O₂ between 60th and 90th min of 3 h study protocol. Plasma lipid peroxides (LOOH) and uric acid (UA) concentration, blood alcohol concentration (BAC) and arterial stiffness (indicated by augmentation index, AIx) were measured before and 30, 60, 90, 120 and 180 min after beverage consumption.

Results

Intake of all alcoholic beverages caused a similar increase of BAC. The oxygen-induced elevation in AIx was similarly reduced in all three groups relative to the control (3.4 ± 1.3%, 5.4 ± 2.2% and 0.2 ± 1.6% vs. 13.7 ± 2.6% for red wine, vodka, beer and control, respectively, 60 min after intake). Exposure to oxygen resulted in increased plasma LOOH in all groups. However, in RW group this increase was lowest (1.1 ± 0.5) in comparison to the vodka (2.1 ± 0.5), beer (1.6 ± 0.3) and control (2.5 ± 0.4 μM/L H₂O₂). 60 min after intake of RW and beer plasma UA significantly increased (34 ± 4 and 15 ± 3) in contrast to vodka and control (−6 ± 2 and −8 ± 2 μmol/L).

Conclusion

All three alcoholic beverages provided similar protection against oxygen-induced increase in arterial stiffness, probably due to central vasodilatatory effect of alcohol itself, but only RW provided protection against oxygen-induced oxidative stress.     

Effects of moderate consumption of white wine on weight loss in overweight and obese subjects

BACKGROUND: Patients on dietary, weight-reducing treatment commonly are advised against alcohol consumption. In light of the widespread use of alcoholic beverages and the well-established benefits of light to moderate alcohol consumption in risk reduction, a revision of dietary treatment recommendations may be warranted. OBJECTIVE: To investigate whether daily consumption of moderate amounts of alcohol influences the effectiveness of an energy-restricted diet in overweight and obese subjects. DESIGN: A prospective randomized clinical trial was conducted, with a 3-months intervention period and two isocaloric dietary regimens containing 6.3 MJ (1500 kcal) each, one with 10% of energy from white wine and one with 10% of energy from grape juice. The trial was performed in obese subjects being recruited from the Obesity Outpatient Clinic at the University Hospital, Ulm, who all habitually consumed moderate amounts of alcohol. Out of 87 patients, 49 were eligible to participate and 40 completed the study (age 48.1+/-11.4 y, BMI 34.2+/-6.4 kg/m(2)). Efficacy parameters were body weight and biomarkers of good health. RESULTS: All subjects achieved significant body weight reduction. Weight loss in the grape juice group and white wine group was 3.75+/-0.46 and 4.73+/-0.53 kg, respectively. Percent body fat, waist circumference, blood pressure, blood glucose, insulin, triglycerides, and cholesterol were reduced. The antioxidant status was unchanged, as were liver enzyme activities and other safety parameters. There were no significant differences between the groups. CONCLUSIONS: An energy-restricted diet is effective in overweight and obese subjects used to drinking moderate amounts of alcohol. A diet with 10% of energy derived from white wine is as effective as an isocaloric diet with 10% of energy derived from grape juice.     

Age associated oxidative damage in RBC and serum of humans

ObjectiveTo evaluate the level of lipid-protein damage and antioxidant status in red blood corpuscle (RBC) and serum of healthy individuals to correlate between oxidative damage with the aging process.MethodsTwenty healthy individuals of each age group (11–20; 21–30; 31–40; 41–50; and 51–60 years old) were selected randomly. Blood samples were drawn by medical practitioner and serum was separated and RBC was isolated from blood samples. Malondialdehyde (MDA), protein carbonyls (PC) level were evaluated to determine the lipid and protein damage in RBC and serum. superoxide dismutase (SOD), catalase (CAT), glutathione and glutathione dependent enzymes were estimated to evaluate the antioxidant status in RBC and serum.ResultsIncreased MDA and PC levels strongly supported the increased oxidative damage in elderly subject than young subjects. The results indicated that, balance of oxidant and antioxidant systems in RBC and serum shifts in favor of accelerated oxidative damage during aging.ConclusionsOxidative stress in RBC and serum may particular interest in aging and may play important role in immunosenescence.     

Effect of raisin consumption on oxidative stress and inflammation in obesity

Aim: Oxidative stress can initiate increased inflammation that elevates risk for cardiovascular disease. The objective of this study was to determine the effects of daily consumption of raisins on markers of oxidative stress, inflammation and endothelial activation in response to an acute high‐fat meal in overweight individuals. Methods: Seventeen overweight men and women consumed 90 g raisins or isocaloric placebo (264 kcal/day) for 14 days in a randomized, crossover design while following a low‐flavonoid diet. The oxidative [urinary 8‐iso‐prostaglandin‐F_2α (8‐epi PGF_2α) and serum oxygen radical absorbance capacity (ORAC)], inflammatory (serum C‐reactive protein and interleukin‐6), endothelial (serum soluble intercellular adhesion molecule‐1 and soluble vascular cell adhesion molecule‐1, sVCAM‐1) and metabolic [free fatty acids (FFAs), triacylglycerol, glucose and insulin] response to four high‐fat (53%) meals was tested pre‐ and postintervention. Results: Urinary 8‐epi PGF_2α decreased (?22%) and fasting ORAC increased (+3%) after both interventions combined. Fasting protein‐free ORAC was modestly (+3.5%) higher during the raisin than the placebo intervention. Neither the meals nor the raisins consistently induced fasted markers of inflammation or endothelial dysfunction. Gender influenced postprandial metabolic responses in that males responded with higher serum FFAs, sVCAM‐1 and glucose compared with females. Conclusions: Serum antioxidant capacity was modestly increased by daily raisin consumption, but this did not alter fasted or postprandial inflammatory response in these relatively healthy but overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress.     

Effect of moderate white wine consumption on serum IgA and plasma insulin under fasting conditions

BACKGROUND/AIMS: The present study aims to investigate the contribution of alcohol toxicity to the development of malnutrition by assessing the effect of consuming a moderate amount of white wine on plasma insulin and serum IgA under fasting conditions. METHODS: A total of 5 non-alcoholic males aged between 19 and 22 years participated in the current investigation. The experimental procedure required participants to undergo a 6-hour fast before ingesting 4 standard units of alcohol (40 g) in the form of white wine over a 120-min period. The level of blood alcohol, plasma insulin and serum IgA was assessed at 30-min intervals across the 120-min experimental period. RESULTS: Consuming alcohol promotes a significant increase in serum IgA in the absence of any change in plasma insulin or ketone production in fasted individuals. CONCLUSION: White wine prior to a meal does not promote glucose metabolism and utilization and may increase the risk of developing a transient diabetic condition due to an alteration in energy metabolism.     

Beyond the French paradox: the impact of moderate beverage alcohol and wine consumption in the prevention of cardiovascular disease

Alcohol beverages, particularly red wine, when consumed in moderation reduce the risk of acute CVD and death. Important questions and issues, however, still remain, including the role of beverage type, pattern of drinking, and the risk that moderate drinking can lead to problem drinking. The mechanism for alcohol beverage benefit is complex, and includes an independent benefit of ethyl alcohol. The multiplicity of effects identified for the non-alcohol components of red wine, play a role in improved endothelial physiology and enhance vascular homeostasis. CAD begins in early life, and it progresses over decades. As the complexity of vascular pathology changes with time, so may the healthful effects of alcohol and non-alcohol wine components also vary. Prospective studies of alcohol or wine consumption in the young, middle, and older aged persons would be interesting, but they are laden with obvious sociologic complexities. Meanwhile, it is prudent for physicians to discuss the harmful effects of alcohol with their patients, while at the same time, not discourage a potentially healthy practice of wine in moderation (e.g., with meals). The current literature is consistent in that heavy drinkers would be better off to reduce drinking or abstain, and abstainers or light drinkers, should be advised to avoid heavy drinking [13]. Whether moderate alcohol consumption can be characterized as a pharmacologic intervention or a dietary intercession may be a matter of opinion. I would rather like to believe that the growing scientific interest in wine and better health is a part of adopting a healthy lifestyle that connects our society with nature, to sustain and enhance human life.     

左西孟旦对心肌细胞氧化应激损伤的保护作用

目的研究左西孟旦对心肌细胞氧化应激损伤的保护作用。方法1、MTT法检测不同浓度的左西孟旦以及H2O2对大鼠心肌细胞生存率的影响。2、光镜观察左西孟旦以及H2O2对大鼠心肌细胞形态学的影响。3、流式细胞仪检测左西孟旦以及H2O2对大鼠心肌细胞凋亡的影响。结果1、MTT显示：①浓度为0.03—0.24umol/L的左西孟旦加入正常大鼠心肌细胞后,测得其吸光度值与空白对照组吸光度值接近,并没有促进增殖的作用;②当加入浓度＞0.3umol/L的左西孟旦后测得细胞吸光度值明显低于空白对照组;③H2O2500umol/L和1000umol/L处理大鼠心肌细胞吸光度的值明显低于空白对照组;④预先加入左西孟旦进行预处理的心肌细胞的吸光度较单加入H2O2的吸光度的值明显升高且与浓度呈正相关。2、光镜下观察：①单纯加入左西孟旦组的心机细胞呈现梭形,呈放射状或栅栏状排列,浓度增加未见细胞伪足收缩及胞体变圆。②加入H2O2500 umol/L和1000 umol/L后,随H2O2浓度的增加,胞体变圆,伪足收缩的细胞增多。③有左西孟旦保护的心肌细胞,胞体变圆,伪足收缩的细胞数量与浓度呈相关性,左西孟旦浓度越高,胞体变圆,伪足收缩的细胞越少。3、流式细胞结果显示：①空白对照组：早期凋亡为0.31%,晚期凋亡6.88%,坏死的心肌细胞4.65%,存活的心肌细胞88.16%。②H2O2 1000umol/L组：早期凋亡为1.52%,晚期凋亡8.03%,坏死的心肌细胞7.66%,存活的心肌细胞82.79%。③Levo0.24umol/L H2O21000umol/L组：早期凋亡为0.44%,晚期凋亡6.48%,坏死的心肌细胞4.95%,存活的心肌细胞88.13%。结论 左西孟旦对大鼠心肌细胞氧化损伤有保护作用,且0.24 umol/L组作用较0.03 umol/L组作用更明显。     

Age-related reduction of NO availability and oxidative stress in humans

Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normotensive and hypertensive individuals. In 47 normotensive subjects and 49 patients with essential hypertension, we evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial sodium nitroprusside (1, 2, and 4 microg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-independent vasodilator and an endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower (P<0.01) in hypertensive patients compared with control subjects. Moreover, in both groups, endothelium-dependent vasodilation declined with aging. In normotensive subjects, the inhibiting effect of L-NMMA on response to acetylcholine decreased in parallel with advancing age, whereas vitamin C increased vasodilation to acetylcholine in only the oldest group (age >60 years). In young hypertensive patients (age <30 years), vasodilation to acetylcholine was sensitive to L-NMMA, whereas in hypertensive patients age >30 years, vitamin C enhanced endothelium-dependent vasodilation and restored the inhibiting effect of L-NMMA on response to acetylcholine. In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-related reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.     

Enhanced oxidative stress in GH-transgenic rat and acromegaly in humans

BackgroundExcessive oxidative stress plays a causal role in various diseases such as diabetes, hypertension, atherosclerosis, and heart failure. Acromegaly is a pathological condition associated with excess growth hormone (GH) and insulin-like growth factor-I (IGF-I) and a high prevalence of diabetes, hypertension, atherosclerosis, and heart failure; resulting in premature death. We hypothesized that these conditions may be associated with increased oxidative stress.Objective and methodsWe explored the oxidative stress levels in the serum and tissues of GH-transgenic rats as an animal model for acromegaly. We also measured the oxidative stress levels in the serum of patients with acromegaly and age-, sex-, and BMI-matched control subjects. We examined the effects of GH and IGF-I on reactive oxygen species (ROS) production in C2C12 myocytes.ResultsThe levels of an oxidative stress marker, serum thiobarbituric acid reactive substances (TBARS) were increased in the GH-transgenic rats. Further, tissue oxidative stress damage was enhanced in the cardiomyocytes and vascular smooth muscle cells in the aorta of the GH-transgenic rats. In addition, serum TBARS levels and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were increased in acromegaly in humans. IGF-I but not GH induced ROS production in C2C12 myocytes in vitro.ConclusionsThese data indicate that the increased levels of IGF-I are associated with enhanced oxidative stress in rats and humans. In addition, increased ROS may play an important role in the complications and premature death in acromegaly.     

Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress

Abstract Aims/hypothesis. Oxidative stress plays an important role in diabetic vascular complications. It has been shown that an imbalance in the ratio of nitric oxide: superoxide anion, because of a prevalence of superoxide anion, leads to an alteration in vascular reactivity. In this condition peroxynitrite production, resulting from the reaction between nitric oxide and superoxide, could increase. Peroxynitrite is responsible for nitration of tyrosine residues in proteins. Therefore, the presence of nitrotyrosine in plasma proteins is considered indirect evidence of peroxynitrite production. The aim of this study was to demonstrate the presence of nitrotyrosine in the plasma of patients with Type II (non-insulin-dependent) diabetes mellitus and to correlate its concentrations with the plasma concentrations of glucose and antioxidant defenses. Methods. A total of 40 Type II diabetic patients and 35 healthy subjects were enrolled, and glycaemia, plasma nitrotyrosine, total antioxidant parameter and glycated haemoglobin were measured. Nitrotyrosine was detected by ELISA with a detection limit of 10 nmol/l. Results. Nitrotyrosine was found in the plasma of all diabetic patients (means ± SD = 0.251 ± 0.141 μmol/l), whereas it was not detectable in the plasma of healthy control subjects. Nitrotyrosine plasma values were correlated with plasma glucose concentrations (r = 0.38, p < 0.02) but not with total antioxidant parameter or glycated haemoglobin. Total antioxidant parameter was reduced in diabetic patients (p < 0.01). Conclusions. The presence of nitrotyrosine in the plasma of diabetic patients indicates that peroxynitrite is generated in diabetes, suggesting a possible involvement of peroxynitrite in the development of diabetic complications. [Diabetologia (2001) 44: 834–838] Received: 6 October 2000 and in revised form: 9 February 2001     

Prevention of cardiovascular risk by moderate alcohol consumption: epidemiologic evidence and plausible mechanisms

An inverse association between moderate alcohol intake and cardiovascular risk, in particular coronary disease and ischemic stroke, has been shown in many epidemiologic studies. In addition, several other diseases are also known to occur less frequently in moderate drinkers than in non-drinkers, whereas excess of drinking is invariably harmful. However, some concern has been recently raised about the possibility that at all dosages the harm of alcohol could overcome its beneficial effects. We present here the epidemiologic and mechanistic evidence to support the protective effect of moderate alcohol intake against cardiovascular disease and all-cause mortality.     

Propofol and in vivo oxidative stress: effects of preservative

Reactive oxygen species are associated with tissue inflammation and injury. Our laboratory has demonstrated that ethane, a stable product of lipid peroxidation, in exhaled breath can be used to measure total body oxidative stress. An ischemia-reperfusion model of lung injury in sheep has been studied in which pulmonary and bronchial lung perfusion could be interrupted and restored. The goal of this study was to investigate whether two commercial formulations of propofol and the individual components of the commercial formulations attenuated the oxidative stress produced in this model. Breath ethane and breath carbon monoxide were measured as biomarkers of oxidative stress that occur at reperfusion of ischemic tissue. Data were analyzed by a standard least-squares-fit model. One of the formulations for propofol, which contained the preservative ethylenediaminetetraacetic acid (EDTA), was found to decrease the overall level of oxidative stress in sheep. Furthermore, while several models of severe lung injury demonstrate additional production of reactive oxygen species, our model of ischemia/reperfusion of lung tissue did not.     

Experimental evidence for the cardioprotective effects of red wine

Both epidemiological and experimental studies have revealed that intake of wine, particularly red wine, in moderation protects cardiovascular health; however, the experimental basis for such an action is not fully understood. Because all types of red wine contain varying amounts of alcohol and antioxidants, it is likely that the cardioprotective effect of red wine is due to both these constituents. In view of its direct action on the vascular smooth muscle cells, alcohol may produce coronary vasodilation in addition to attenuating oxidative stress by its action on the central nervous system. The antioxidant components of red wine may provide cardioprotection by their ability to reduce oxidative stress in the heart under different pathological conditions. Mild-to-moderate red wine consumption improves cardiac function in the ischemic myocardium through the protection of endothelial function, the expression of several cardioprotective oxidative stress-inducible proteins, as well as the activation of adenosine receptors and nitrous oxide synthase mechanisms.     

Evidence of oxidative stress in chronic heart failure in humans

Chronic heart failure (CHF) due to coronary artery disease (CAD)has been shown to be associated with increased plasma thiobarbituricreactive substances (TBARS) and reduced plasma thiol (PSH) concentrations,suggesting oxidative stress (OS). The aims of the present studieswere (a) to determine whether OS is due to CAD or CHF per seand (b) to determine if a wider range of more specific markersof OS are abnormal in CHF. In the first study, two groups of patients (n = 15 each) werecompared. Group 1 (11 male, mean age 56 years) had CHF due toCAD and group 2 (12 male, mean age 53 years) had non-CAD CHF.Median plasma TBARS in controls was 7.6 nmol . ml^–1 ,10.0 nmol . m^–1 in group 1 and 9.3 nmol. ml^–1 ingroup 2 (P < 0.01 both groups vs control). Median PSH was505 384 and 364 nmol. ml^–1 (P < 0.05 and P < 0.01vs control) respectively. Fifty-three patients with CHF were recruited in the second study.Malondialdehyde and PSH were 10.3 and 409 nmol. ml^–1 respectively,compared to control values of 7.9 and 560 nmol. ml^.1 (both P< 0.001). The median values for the following additionalmeasures of OS in controls and patients were: erythrocyte superoxidedismustase 131 vs 114 U . l^–1 (P = 0.005); caeruloplasminoxidase 97 vs 197 U. l^–1 (P < 0.01); erythrocyte glutathione1.56 nmol . ml^–1 vs 1.77 nmol . ml^–1 (P < 0.02);plasma conjugated dienes 0.28 vs 0.33 optical density units(P = ns). Chronic heart failure, regardless of aetiology, is associatedwith abnormalities of a range of markers of OS.     

Polyphenols synergistically inhibit oxidative stress in subjects given red and white wine

Aim of this study was to analyse the relationship between the plasma levels of polyphenols and the antioxidant activity of red and white wine. Twenty healthy subjects (HS) were randomly allocated to drink 300 ml of red (n = 10) or white n = 10 wine for 15 days. Ten HS who refrained from any alcohol beverage for 15 days were used as control. Urinary PGF-2alpha-III, a marker of oxidative stress and plasma levels of polyphenols were measured. Urinary PGF-2alpha-III significantly fell in subjects taking wine with a higher percentage decrease in subjects given red wine (-38.5 +/- 6%, p < 0.001) than in those given white wine (-23.1 +/- 6%). Subjects taking red wine had higher plasma polyphenols than those taking white wine (1.9 +/- 0.6 microM versus 1.5 +/- 0.33 microM, p < 0.001). Plasma polyphenols were inversely correlated with urinary PGF2alpha (r = 0.77, p < 0.001). No changes of urinary isoprostanes were observed in subjects who refrained from wine intake. In vitro study demonstrated that only a mixture of polyphenols, all in a range corresponding to that found in human circulation, inhibited LDL oxidation and PKC-mediated NADPH oxidase activation. Such inhibitory effects were more marked using the concentrations of polyphenols detected in human circulation after red wine intake. This study shows that red wine is more antioxidant than white wine in virtue of its higher content of polyphenols, an effect that may be dependent upon a synergism among polyphenols.     

Diabetic cardiomyopathy and its mechanisms: Role of oxidative stress and damage

Diabetic cardiomyopathy as an important threat to health occurs with or without coexistence of vascular diseases. The exact mechanisms underlying the disease remain incompletely clear. Although several pathological mechanisms responsible for diabetic cardiomyopathy have been proposed, oxidative stress is widely considered as one of the major causes for the pathogenesis of the disease. Hyperglycemia‐, hyperlipidemia‐, hypertension‐ and inflammation‐induced oxidative stress are major risk factors for the development of microvascular pathogenesis in the diabetic myocardium, which results in abnormal gene expression, altered signal transduction and the activation of pathways leading to programmed myocardial cell deaths. In the present article, we aim to provide an extensive review of the role of oxidative stress and anti‐oxidants in diabetic cardiomyopathy based on our own works and literature information available.     

The effects of oxidative stress on the liver sieve

BACKGROUND/AIMS: Oxidative stress is implicated in the pathogenesis of age-related and disease-associated changes in the hepatic sinusoid. We studied the effects of oxidative stress on the morphology of the liver, focusing specifically on the hepatic sinusoidal endothelium (the 'liver sieve'). METHODS: The effects of tert-butyl hydroperoxide on the intact liver and isolated sinusoidal endothelial cells were assessed by electron microscopy, immunohistochemistry and biochemical analysis. RESULTS: Immunohistochemistry revealed a dose-dependent increase in peri-sinusoidal 3-nitrotyrosine staining, particularly in the regions adjacent to the portal triads. Electron microscopy showed dose-dependent formation of large intracellular gaps in the sinusoidal endothelium with reduction in the diameter of the remaining endothelial fenestrations. Activated Kupffer cells extending processes through the fenestrations to contact hepatocytes were noted. Biochemical analysis of total liver tissue showed no significant changes in malondialdehyde content but a decrease in the ratio of GSH to GSSG. tert-Butyl hydroperoxide administered directly onto isolated liver sinusoidal endothelial cells was associated with similar gap formation, indicating a direct effect on the endothelial cells by tert-butyl hydroperoxide. CONCLUSIONS: Oxidative stress selectively damages hepatic sinusoidal endothelial cells. This has implications for those processes associated with changes in the sinusoidal endothelium such as ageing, cirrhosis and exposure to hepatotoxins.     

大鼠中度液压颅脑损伤后氧化应激反应的实验研究

目的：通过建立大鼠中度颅脑液压损伤模型,检测损伤病灶生化指标脂质氧化终产物丙二醛及抗氧化剂谷胱甘肽含量的变化,探讨其与继发性脑损伤之间的关系,为后续研究提供实验基础。方法雄性Sprague-Dawley大鼠48只,随机分成中度颅脑损伤组（mTBI组）和假手术组（sham-TBI组）,各24只。以液压中度颅脑损伤指标致伤TBI组。并于伤后6h、24h处死大鼠,通过ELISA技术测定抗氧化剂谷胱甘肽和脂质氧化产物丙二醛在两组的不同表达,采用独立样本t检验评价大鼠颅脑创伤后的氧化应激损伤。结果mTBI组脑组织见损伤灶及蛛网膜下腔出血,HE染色后可见神经元损伤核固缩,细胞坏死呈空泡状,而sham-TBI组未见神经元损伤表现。TBI后mTBI组中丙二醛浓度较sham-TBI组显著升高,随伤后时间延长丙二醛浓度显著升高（t6h＝6.49,P＜0.01;t24h＝11.22,P＜0.01）;而TBI后mTBI组谷胱甘肽浓度显著低于sham-TBI组,随伤后时间延长谷胱甘肽浓度显著降低（t6h＝9.25,P＜0.01;t24h＝11.24,P＜0.01）。结论液压颅脑损伤模型致伤能量能够测量,稳定性及重复性良好,伤情可能分级。中度闭合性颅脑外伤可导致脑组织病理学改变和氧化应激损伤,且氧化应激损伤指标与脑损伤时间有关,外伤后早期阻断氧化应激过程可以起到脑保护作用。