白藜芦醇对大鼠局灶性脑缺血再灌注的治疗作用

目的:观察白藜芦醇对大鼠局灶性脑缺血再灌注损伤的治疗作用及可能的机制。方法:将SD大鼠随机分为2组:对照组(n=16),白藜芦醇组(n=16)。对照组再灌注即刻腹腔给予0.5 ml生理盐水,白藜芦醇组再灌注即刻腹腔给予20 mg/kg白藜芦醇。再灌注22小时后,进行神经功能学评分、脑梗死容积测定,用分光光度仪测定脑组织溶浆中SOD、MDA和MPO的含量。结果:再灌注22小时后,白藜芦醇治疗组可以改善大鼠神经功能学评分和降低脑梗死面积(P<0.05),同时可以增加脑组织溶浆中SOD的活性,降低MDA和MPO的含量。结论:白藜芦醇通过减轻白细胞的浸润、提高自由基的清除率对大鼠局灶性脑缺血再灌注损伤发挥治疗作用。     

Effect of glycerol-induced acute renal failure and di-2-ethylhexyl phthalate on the enzymes involved in biotransformation of xenobiotixs.

The effects of di-(2-ethylhexyl)-phthalate (DEPH) on the levels of cytochrome P-450 and b5 monooxygenases were studied in the rat kidney and liver in acute renal failure induced by glycerol. Intramuscular injection of glycerol (50%,10 ml x kg(-1)) to rats produced proximal tubular damage and acute renal failure. The indicators of renal function, serum urea and creatinine significantly increased (480 and 350 percent, respectively). In control and glycerol-treated animals DEPH had no significant effect on the concentrations of serum urea and creatinine. Twenty-four hours after glycerol injection the total amount of cytochrome P-450 and b5 significantly decreased in renal but increased in liver microsomal fractions. Moreover, 48 and 72 hours after glycerol injection the level of cytochrome P-450 and b5 significantly increased in both organs. A single dose of DEPH (2 ml x kg(-1), i.p.) also elevated the total cytochrome P-450 and b5 in control animals. This enhancing effect of DEPH was additive to that of glycerol in glycerol-induced acute renal failure. These results indicate that DEPH and glycerol evoked pathological changes may affect the metabolism of xenobiotics plus endogenous hormones in the liver and in kidney.     

The effect of resveratrol on surgery-induced peritoneal adhesions in an experimental model

Adhesion formation is a common cause of complications following surgery. The aim of this study was to investigate the effect of resveratrol on intra-abdominal adhesion prevention in a rat model. Twenty one Wistar-Albino rats weighing 200-250 g were assigned to three groups, of 7 rats each. After a midline laparotomy was performed, a 1 cm area of the ceacum was abraded in two of the groups. They were then given either resveratrol (Group 1), or saline (Group 2) intraperitoneally. Group 3 rats (sham operation) received no treatment, without the serosal damage. On the 14th day, the rats were killed and the adhesion score was determined according to Mazuji's adhesion grade scale. The tissue levels of malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) were measured. The mean Mazuji's adhesion grade in the resveratrol group was 1.0 +/- 0.0, in the saline group 2.57 +/- 1.51, and zero in the sham operated group (p < 0.05 between the resveratrol group and saline group comparison). The levels of MDA and NO in the resveratrol group were significantly lower than those of the saline group (p < 0.001). The level of GSH in the resveratrol group was significantly higher than in the saline and sham operated groups (p < 0.001 and p < 0.001, respectively). Introduction of resveratrol into the peritoneal cavity at the time of surgery reduced adhesion formation effectively in this model. Resveratrol probably acts through reduction of lipid peroxidation products.     

The effects of resveratrol administration on lipid oxidation in experimental renal ischemia-reperfusion injury in rats

ABSTRACT

We investigated how resveratrol affects lipid oxidation during experimental renal ischemia-reperfusion injury in rats. We used 48 adult male rats assigned to five groups: group 1, control; group 2, renal ischemia; group 3, renal ischemia + reperfusion; group 4, resveratrol + renal ischemia; group 5, resveratrol + renal ischemia + reperfusion. Plasma and renal tissue malondialdehyde (MDA), and erythrocyte and renal tissue glutathione (GSH) levels were measured and histologic changes in the renal tissue were examined. Ischemia-reperfusion affected the MDA-GSH balance adversely and caused histopathological changes in the renal tissue of the ischemia and ischemia + reperfusion groups. Resveratrol treatment normalized MDA and GSH levels as well as the histopathology that occurred in the renal tissue of the ischemia and ischemia + reperfusion groups.     

Effects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats

The present study investigated the effects of resveratrol (RV), a polyphenol with potent antioxidant properties, on oxidative stress parameters in liver and kidney, as well as on serum biochemical parameters of streptozotocin (STZ)-induced diabetic rats. Animals were divided into six groups (n = 8): control/saline; control/RV 10 mg/kg; control/RV 20 mg/kg; diabetic/saline; diabetic/RV10 mg/kg; diabetic/RV 20 mg/kg. After 30 days of treatment with resveratrol the animals were sacrificed and the liver, kidney and serum were used for experimental determinations. Results showed that TBARS levels were significantly increased in the diabetic/saline group and the administration of resveratrol prevented this increase in the diabetic/RV10 and diabetic/RV20 groups (P < 0.05). The activities of catalase (CAT), superoxide dismutase (SOD) and aminolevulinic acid dehydratase (δ-ALA-D) and the levels of non protein thiols (NPSH) and vitamin C presented a significant decrease in the diabetic/saline group when compared with the control/saline group (P < 0.05). The treatment with resveratrol was able to prevent these decrease improving the antioxidant defense of the diabetic/RV10 and diabetic/RV20 groups (P < 0.05). In addition, the elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamiltransferase (γ-GT) activities as well as in levels of urea, creatinine, cholesterol and triglycerides observed in the diabetic/saline group were reverted to levels close to normal by the administration of resveratrol in the diabetic/RV10 and diabetic/RV20 groups (P < 0.05). These findings suggest that resveratrol could have a protector effect against hepatic and renal damage induced by oxidative stress in the diabetic state, which was evidenced by the capacity of this polyphenol to modulate the antioxidant defense and to decrease the lipid peroxidation in these tissues.     

白藜芦醇通过调节SIRT1/NF-κB通路减轻力竭训练致大鼠肾脏炎症反应

白藜芦醇是天然存在的沉默信息调节因子2相关酶1(sirtuin1，SIRT1)小分子激动剂，其肾的保护作用已在多种肾疾病动物模型中得到了验证。然而，白藜芦醇是否能够改善力竭训练导致的大鼠肾损伤，以及是否通过SIRT1/NF κB信号通路调节运动性肾损伤大鼠肾炎症反应，尚缺乏系统研究。本研究将32只SD大鼠随机分为安静对照组(Con组)，白藜芦醇组（Rsv组），力竭运动组（Ex组），力竭运动+白藜芦醇组（Ex+Rsv组）。Rsv和Ex+Rsv组每天灌胃50 mg/kg体重剂量的白藜芦醇， Ex和Ex+Rsv组进行4周力竭训练，最后1次训练后24 h取材。本研究结果显示，与Con组相比，Ex组大鼠Scr（175.66 ± 16.08 vs.153.34 ± 8.67，P < 0.01）、BUN（6.67 ± 0.53 vs.5.37 ± 019，P < 0.01）和尿NGAL（9.01 ± 0.18 vs.7.48 ± 0.31，P < 0.01）水平均显著升高，Ex组大鼠肾组织NF κB P65在蛋白质水平表达显著升高（0.77 ± 010 vs. 0.27 ± 0.03，P < 0.01）；各组大鼠肾组织SIRT1在蛋白质水平表达上，Rsv组显著高于Con组（0.90 ± 0.14 vs. 0.43 ± 0.15，P < 0.05），Ex+Rsv组显著高于Ex组（1.0 ± 0.28 vs. 0.38 ± 0.12，P< 001）；与Ex组相比，Ex+Rsv组大鼠肾组织NF-κB P65（0.57 ± 0.13 vs. 0.77 ± 0.10，P < 0.05）和Ac-NF-κB P65（0.52 ± 0.13 vs. 0.78 ± 0.11，P < 0.05）在蛋白质水平表达显著降低。以上结果表明，4周大强度力竭运动导致大鼠出现运动性肾损伤，并激活大鼠肾NF-κB的表达。白藜芦醇可显著提高大鼠肾组织SIRT1在蛋白质水平的表达，并增加脱乙酰化作用，降低NF-κB P65蛋白质乙酰化修饰水平，进一步降低NF-κB的表达。白藜芦醇减轻力竭训练致大鼠肾的炎症反应的机制可能与SIRT1/NF-κB通路有关。     

Role of glomerular nitric oxide in glycerol-induced acute renal failure

Myoglobinuric acute renal failure remains one of the least understood clinical syndromes and the mediators involved remain obscure. The aim of the present study was to assess the role of nitric oxide in glycerol-induced acute renal failure under normal conditions and after uninephrectomy. Acute renal failure was induced in rats by injection of 50% glycerol (10 mL x kg(-1) body weight). Half of the animals were subjected to uninephrectomy two days before glycerol injection. Two days after the induction of acute renal failure, glomeruli from some animals were isolated and glomerular nitrite production was measured. Another group of animals was used for acute clearance studies. In this case, the effect of infusing either L-NAME or L-arginine was assayed. Glomerular nitrite production was significantly decreased in glycerol-induced acute renal failure. Glomeruli from uninephrectomized animals showed an increase in nitrite production, both in normal conditions and after glycerol injection, as compared with glomeruli from non-nephrectomized animals. L-NAME infusion worsened renal function in all the study groups, but more slowly in animals with glycerol-induced acute renal failure than in control rats. In uninephrectomized animals L-NAME reduced renal function more than in animals with two kidneys. In conclusion, in this model of acute renal failure the decrease in glomerular nitric oxide production plays an important role in the decrease in renal function. After uninephrectomy, an increase in glomerular nitric oxide synthesis plays a protective role against glycerol-induced acute renal failure.     

Chemomodulatory effect of Ficus racemosa extract against chemically induced renal carcinogenesis and oxidative damage response in Wistar rats

Ferric nitrilotriacetate (Fe-NTA) is a well-known renal carcinogen. In this communication, we show the chemopreventive effect of Ficus racemosa extract against Fe-NTA-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [(3)H] incorporation into renal DNA. It also enhances DEN (N-diethylnitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors. Treatment of rats orally with F. racemosa extract (200 and 400 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (P<0.001) and incidence of tumors. Renal glutathione content (P<0.01), glutathione metabolizing enzymes (P<0.001) and antioxidant enzymes were also recovered to significant level (P<0.001). Thus, our data suggests that F. racemosa extract is a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rats.     

Protective effect of resveratrol against doxorubicin-induced cardiac toxicity and fibrosis in male experimental rats

The possible effectiveness of resveratrol, a polyphenol present in different plants comprising berries, grapes and peanuts, on the prevention of doxorubicin-induced cardiac toxicity and fibrosis was investigated. Forty adult male Wistar albino rats were divided into four groups. Group I received normal saline, group II gavaged with resveratrol (20 mg/kg, daily for 4 weeks), group III received doxorubicin (2.5 mg/kg i.p. in six injections for 2 weeks; accumulative dose of 15 mg/kg), and group IV received doxorubicin?+?resveratrol (starting resveratrol intake 2 weeks before doxorubicin administration). Resveratrol significantly alleviated the increase in left ventricular lipid peroxidation, hydroxyproline, and tumor necrosis factor alpha levels as well as serum creatine kinase-myocardial band (CK-MB) activity and prevented the decrease in body and heart weights in doxorubicin-treated group. However, a marked protection against reduced glutathione content depletion and superoxide dismutase activity reduction was observed in the left ventricles of rats pretreated with resveratrol in combination with doxorubicin. Resveratrol also ameliorated the up-regulation of left ventricular caspase-3 and transforming growth factor-beta1 gene expression as well as left ventricular histopathological changes including necrosis and fibrosis induced by doxorubicin. Collectively, our results suggest that resveratrol provides a significant protection against doxorubicin-induced cardiotoxicity and fibrosis in rats. Therefore, it may be used as a promising cardioprotective agent in patients treated with doxorubicin due to malignant diseases. So, further clinical trials are required to confirm these findings.     

Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats

Iron nitrilotriacetate (Fe-NTA), a chief environmental pollutant, is known for its extensive toxic manifestations on renal system. In the present study, caffeic acid, one of the most frequently occurring phenolic acids in fruits, grains, and dietary supplements was evaluated for its shielding effect against the Fe-NTA-induced oxidative, inflammatory, and pathological damage in kidney. Fe-NTA was administered (9 mg Fe/kg body weight) intraperitoneally to the Wistar male rats on 20th day while caffeic acid was administered orally (20 and 40 mg/kg body weight) before administration of Fe-NTA. The intraperitoneal administration of Fe-NTA-enhanced lipid peroxidation, xanthine oxidase, and hydrogen peroxide generation with reduction in renal glutathione content, antioxidant enzymes, viz., catalase, glutathione peroxidase, and glutathione reductase. A sharp elevation in the levels of myloperoxidase, blood urea nitrogen (BUN), and serum creatinine has also been observed. Tumor promotion markers viz., ornithine decarboxylase (ODC) and [(3)H] thymidine incorporation into renal DNA were also significantly increased. Treatment of rats orally with caffeic acid (20 and 40 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.001), lipid peroxidation (P < 0.001), γ-glutamyl transpeptidase (P < 0.01), and H(2)O(2) (P < 0.01). There was significant recovery of renal glutathione content (P < 0.001) and antioxidant enzymes (P < 0.001). There was also a reversal in the enhancement of renal ODC activity, DNA synthesis, BUN, and serum creatinine (P < 0.001). All these changes were supported by histological observations. The results indicate that caffeic acid may be beneficial in ameliorating the Fe-NTA-induced oxidative damage and tumor promotion in the kidney of rats.     

有氧运动和白藜芦醇对2型糖尿病大鼠肾脏JAK2及TGF-β1的影响

目的: 研究有氧运动和白藜芦醇对2型糖尿病大鼠肾脏Janus激酶2(JAK2)及转化生长因子-β1(TGF-β1)表达的影响,探讨运动与白藜芦醇改善糖尿病肾损伤的可能作用机制。方法: SD大鼠经5周高糖高脂饲料喂养加腹腔注射链脲佐菌素(STZ)建立糖尿病模型后,将糖尿病大鼠随机分为糖尿病安静组(DC组),糖尿病运动组(DE组),糖尿病药物组(DR组)和糖尿病运动药物组(DER组),每组各12只,另设正常对照组(NC组)。运动组大鼠进行8周的有氧运动(跑速为20 m/min),每天运动60 min,每周运动6 d;药物组大鼠进行8周的白藜芦醇灌胃(每天45 mg/kg,7天/周)。8周末,检测血糖、24 h尿白蛋白(24 h UA)、血肌酐(Scr)、血尿素氮(BUN)的变化;采用荧光定量PCR检测肾脏JAK2 mRNA的表达,免疫组织化学法和Western blot法检测肾脏JAK2和TGF-β1的表达。结果: 8周干预后,与NC组相比, DC组血糖浓度、24 h UA、Scr、BUN均显著上升(P＜0.05),肾组织病理损伤加重,肾组织TGF-β1、JAK2和JAK2 mRNA的表达均明显增加(P＜0.05)。与DC组相比,DE、DR和DER组血糖浓度、24 h UA、Scr、BUN均显著下降(P＜0.05),肾组织病理损伤减轻,肾组织TGF-β1、JAK2和JAK2 mRNA的表达均明显减少(P＜0.05),且DER组的降低更显著,与DE、DR组相比差异有显著性(P＜0.05)。结论: 有氧运动、白藜芦醇及联合干预可能通过下调肾脏JAK2 mRNA表达,抑制JAK2蛋白的合成,使TGF-β1表达减少,从而改善糖尿病大鼠肾脏损伤的病理性变化。有氧运动联合白藜芦醇干预减轻肾脏病理损伤的效果优于单一的有氧运动或白藜芦醇干预。     

白藜芦醇通过Pi3K/AKT 通路抑制胃癌SGC-7901 细胞增殖和迁移

目的:验证白藜芦醇是否可以抑制胃癌SGC-7901细胞增殖和迁移及其信号通路。方法:用不同浓度白藜芦醇干预SGC-7901细胞,再用LY-294002和IGF-1分别用来抑制和激活Pi3K/AKT通路。MTT法测细胞增殖,划痕试验和Transwell试验测细胞迁移,Western blot检测细胞迁移相关蛋白(MMP-2、MMP-9)、细胞迁移相关蛋白(P21、P27)、以及AKT、p-AKT的表达情况;结果:相比于对照组,白藜芦醇组胃癌细胞增殖和迁移减弱(P=0.001),p-AKT表达减少(P0.001);LY-294002可以抑制p-AKT的表达(P=0.004),和白藜芦醇一样可以抑制胃癌细胞的增殖和迁移;IGF-1可以显著增加p-AKT的表达(P0.001),可以逆转白藜芦醇对胃癌细胞增殖和迁移的抑制作用。结论:白藜芦醇通过抑制Pi3K/AKT信号通路抑制胃癌细胞增殖和迁移。     

Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure

Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.     

Modulatory influence of dietary resveratrol during different phases of 1,2-dimethylhydrazine induced mucosal lipid-peroxidation, antioxidant status and aberrant crypt foci development in rat colon carcinogenesis

To shed light on the association of lipid peroxidation and antioxidant status with the development of aberrant crypt foci (ACF), we studied the modulatory influence of resveratrol, supplemented in three dietary regimens (initiation, post-initiation and entire period) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were administered DMH (20 mg/kg body weight, s.c.) for 15 weeks and were supplemented with resveratrol (8 mg/kg body weight, p.o. everyday) in three dietary regimens. Intestines and colons were analyzed for the levels of diene conjugates (DC), lipid hydroperoxides (LOOHs) and thiobarbituric acid reactive substances (TBARS). Enzymic antioxidants (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX; glutathione S-transferase, GST; and glutathione reductase, GR) and non-enzymic reserve (reduced glutathione, GSH; ascorbate; and alpha-tocopherol) were also assessed in the intestine and colon. Unsupplemented DMH exposed rats showed significantly decreased levels/activities of tissue DC, LOOHs, TBARS, SOD, CAT, GSH, GR and significantly elevated (P<0.05) GPX, GST, alpha-tocopherol and ascorbate as compared to control rats. Resveratrol supplementation during the entire period of the study resulted in significant (P<0.01) modulation of lipid peroxidation markers and antioxidants status, which were paralleled with ACF suppression, as compared to DMH-alone treated rats. These results indicate that resveratrol effectively inhibits DMH-induced ACF and colonic tumor development.     

Resveratrol Attenuates Diabetic Nephropathy via Modulating Angiogenesis

Angiogenesis plays an important role in the pathogenesis of diabetic nephropathy (DN). In the present study, we investigated the therapeutic potential of resveratrol, a polyphenol with antiangiogenic activity in DN. In a type 1 diabetic rat model, resveratrol treatment blunted the increases of urine albumin excretion, kidney weight and creatinine clearance rate. The increases of glomerular diameter, mesangium accumulation, glomerular basement membrane thickness and renal fibrosis in diabetic rats were also reduced by resveratrol treatment. In the diabetic kidney, increased expression of vascular endothelial growth factor (VEGF), Flk-1 and angiopoietin 2, and reduced expression of Tie-2 were observed. These changes in angiogenic hormones and associated receptors were attenuated by resveratrol treatment. No changes in angiopoietin 1 expression were detected among each group of rats. Resveratrol also significantly downregulated high glucose-induced VEGF and Flk-1 expressions in cultured mouse glomerular podocytes and endothelial cells, respectively. These effects were attenuated by knocking-down silent information regulator 1 (Sirt1) expression. In contrast, upregulation of Sirt1 in cultured endothelial cells reduced Flk-1 expression. Increased permeability and cellular junction disruption of cultured endothelial cells caused by VEGF were also inhibited by resveratrol pretreatment. Taken together, the present study demonstrated that resveratrol may attenuate DN via modulating angiogenesis.     

Resveratrol Protects Against Neurotoxicity Induced by Kainic Acid

Increased oxidative stress has been implicated in the mechanisms of excitotoxicity in hippocampus induced by kainic acid (KA), an excitatory glutamate receptor agonist. Resveratrol, a polyphenolic antioxidant compound enriched in grape, is regarded as an important ingredient in red wine to offer cardiovascular and neural protective effects. This study was designed to investigate whether resveratrol treatment may ameliorate neuronal death after KA administration. Adult Sprague Dawley male rats were treated with KA (8 mg/kg) daily for 5 days and another group was treated similarly with KA plus resveratrol (30 mg/kg/day). Three hr after the last treatment protocol, animals were sacrificed, and brain sections were obtained for histochemical and immunohistochemical identification of neurons, astrocytes and microglial cells. After KA administration, significant neuronal death and activation of astrocytes and microglial cells were observed in the hippocampal CA1, CA3 and polymorphic layer (hilar) of the dentate gyrus (DG) (P < 0.001). The KA-induced hippocampal neuronal damage was significantly attenuated by treatment with resveratrol (P < 0.001). Resveratrol also suppressed KA-induced activation of astrocytes and microglial cells. Since increased oxidative stress is a key factor for KA-induced neurotoxicity, this study demonstrated the ability of resveratrol to act as free radical scavenger to protect against neuronal damage caused by excitotoxic insults.Special issue dedicated to Dr. Lawrence F. Eng.     

白藜芦醇对力竭训练动物能量代谢和抗氧化功能的影响

白藜芦醇具有多种生物学功能和药用价值,例如抗炎、抗衰老、抗病毒、抗肿瘤等。为了探讨白藜芦醇在外源性抗氧化剂方面的开发价值。本研究建立了跑步力竭SD大鼠模型,应用不同浓度的白藜芦醇处理大鼠4周。研究显示,白藜芦醇处理可以剂量依赖性方式提高大鼠的跑步力竭时间(p<0.05)。白藜芦醇处理以剂量依赖方式降低大鼠血清乳酸和尿素氮水平并升高游离脂肪酸水平(p<0.05)。白藜芦醇处理以剂量依赖方式升高大鼠体内超氧化物歧化酶和过氧化氢酶水平,并降低丙二醛水平(p<0.05)。白藜芦醇处理以剂量依赖方式降低血清肌酸激酶、天冬氨酸转氨酶和丙氨酸转氨酶水平(p<0.05)。此外,白藜芦醇明显减轻了大鼠骨骼肌的病理改变。因此,白藜芦醇可提高跑步力竭大鼠的抗疲劳能力,改善能量代谢方式,提高机体抗氧化能力,减少运动损伤。     

Resveratrol inhibition of lipid peroxidation

To define the molecular mechanism(s) of resveratrol inhibition of lipid peroxidation we have utilized model systems that allow us to study the different reactions involved in this complex process. Resveratrol proved (a) to inhibit more efficiently than either Trolox or ascorbate the Fe2+ catalyzed lipid hydroperoxide-dependent peroxidation of sonicated phosphatidylcholine liposomes; (b) to be less effective than Trolox in inhibiting lipid peroxidation initiated by the water soluble AAPH peroxyl radicals; (c) when exogenously added to liposomes, to be more potent than alpha-tocopherol and Trolox, in the inhibition of peroxidation initiated by the lipid soluble AMVN peroxyl radicals; (d) when incorporated within liposomes, to be a less potent chain-breaking antioxidant than alpha-tocopherol; (e) to be a weaker antiradical than alpha-tocopherol in the reduction of the stable radical DPPH*. Resveratrol reduced Fe3+ but its reduction rate was much slower than that observed in the presence of either ascorbate or Trolox. However, at the concentration inhibiting iron catalyzed lipid peroxidation, resveratrol did not significantly reduce Fe3+, contrary to ascorbate. In their complex, our data indicate that resveratrol inhibits lipid peroxidation mainly by scavenging lipid peroxyl radicals within the membrane, like alpha-tocopherol. Although it is less effective, its capacity of spontaneously entering the lipid environment confers on it great antioxidant potential.     

白藜芦醇后处理对大鼠脑缺血再灌注损伤海马CA1区Bax、Bcl-2的影响

摘要 目的：探讨白藜芦醇后处理对大鼠脑缺血再灌注损伤Bax、Bcl-2表达的影响。方法：清洁级雄性SD大鼠60只随机分为假手术组（n=12）、I/R组（n=12）、白藜芦醇组（n=36）,白藜芦醇组按不同剂量分为低剂量、中剂量、高剂量组（10 mg/kg、20 mg/kg、40 mg/kg）,每组12只。假手术组：仅暴露大鼠颈外动脉,不做缺血处理;I/R组：采用改良线栓法制备大鼠大脑中动脉缺血再灌注损伤模型（缺血2 h,再灌注24 h）;白藜芦醇组：造模方法同I/R组,在大鼠缺血2h后,将不同剂量白藜芦醇腹腔注射入大鼠体内,比较各组SD大鼠神经功能缺损评分、采用Western blotting法、免疫组化法对大鼠脑组织缺血侧海马CA1区Bax和Bcl-2表达进行比较。结果：白藜芦醇低、中、高剂量组神经功能缺损评分均低于I/R组,随着白藜芦醇剂量的增加,神经功能缺损评分逐渐降低,其中白藜芦醇高剂量组神经功能缺损评分降低最为明显;白藜芦醇组与I/R组相比,不同剂量白藜芦醇组Bax表达逐渐减少,而Bcl-2表达明显增加,其中以白藜芦醇高剂量组改变最为明显。结论：高剂量白藜芦醇可以降低大鼠神经功能缺损评分,减轻脑缺血再灌注损伤,对大鼠脑缺血再灌注损伤具有保护作用,其机制与Bax、Bcl-2的表达有关。     

Hypolipidemic action of dietary resveratrol,a phytoalexin in grapes and red wine,in hepatoma-bearing rats

Resveratrol is an antioxidant present in grapes and their related products. We investigated whether dietary resveratrol could inhibit the proliferation and metastasis of tumors and hyperlipidemia in Donryu rats subcutaneously implanted with an ascites hepatoma cell line of AH109A. By feeding 10 or 50 ppm resveratrol in the diet to hepatoma-bearing rats for 20 days, solid tumor growth and metastasis tended to be suppressed dose-dependently. Resveratrol (50 ppm) significantly suppressed the serum lipid peroxide level, indicating its antioxidative properties or those of its metabolite(s) in vivo. Resveratrol dose-dependently suppressed both the serum triglyceride and very-low-density lipoprotein + low-density lipoprotein (VLDL + LDL)-cholesterol levels. The hypocholesterolemic action of resveratrol is attributed, at least in part, to an increased excretion of neutral sterols and bile acids into feces. These results suggest that dietary resveratrol is hypolipidemic with a tendency for anti-tumor-growth and anti-metastasis effects in hepatoma-bearing rats.