Metabolic syndrome in the rat: females are protected against the pro-oxidant effect of a high sucrose diet

Metabolic syndrome is more prevalent in men than in women. In an experimental dietary model of metabolic syndrome, the high-fructose-fed rat, oxidative stress has been observed in males. Given that estradiol has been documented to exert an antioxidant effect, we investigated whether female rats were better protected than males against the adverse effects of a high-sucrose diet, and we studied the influence of hormonal status in female rats. Males and females were first fed a sucrose-based or starch-based diet for 2 weeks. In the males, the plasma triglyceride (TG)-raising effect of sucrose was accompanied by significantly lowered plasma alpha-tocopherol and a significantly lowered alpha-tocopherol/TG ratio (30%), suggesting that vitamin E depletion may predispose lipoproteins to subsequent oxidative stress. In males, after exposure of heart tissue homogenate to iron-induced lipid peroxidation, thiobarbituric reactive substances were significantly higher in the sucrose-fed than in the starch-fed rats. In contrast, in sucrose-fed females, neither a decrease in vitamin E/TG ratio nor an increased susceptibility of heart tissue to peroxidation was observed, despite both a significantly decreased heart superoxide dismutase activity (14%) and a significant 3-fold increase in plasma nitric oxide concentration compared with starch-fed females. The influence of hormonal status in female rats was then assessed using intact, ovariectomized, or estradiol-supplemented ovariectomized female rats fed the sucrose or starch diet for 2 weeks. After exposure of heart tissue to iron-induced lipid peroxidation, higher susceptibility to peroxidation was found only in ovariectomized females fed the sucrose diet compared with the starch group and not in intact females or ovariectomized females supplemented with estradiol. Thus, estrogens, by their effects on antioxidant capacity, might explain the sexual difference in the pro-oxidant effect of sucrose diet resulting in metabolic syndrome in rats.     

Influence of dietary carbohydrate on zinc-deficiency-induced changes in oxidative defense mechanisms and tissue oxidative damage in rats

The aim of this study was to determine the effect of dietary carbohydrate type on the expression of zinc (Zn) deficiency in rats with respect to tissue oxidative damage and defense mechanisms. Rats were fed diets containing adequate (+Zn) or low concentrations (-Zn) of Zn. Both fructose- and glucose-based diets were tested. Pair-fed controls were also studied to evaluate changes in the oxidative defense system which are secondary to Zn-deficiency-induced anorexia. Plasma and liver Zn concentrations and CuZn superoxide dismutase activities were lower in the -Zn rats than in the +Zn rats. Liver glutathione (GSH) and disulfide glutathione concentrations were higher in the -Zn rats than in the +Zn rats; this difference was most pronounced in the fructose groups. Liver and heart selenium glutathione peroxidase (Se-GSH-Px) activities were lower in the -Zn-fructose group than in the +Zn-fructose group. Liver Se-GSH-Px activity was higher in the fructose groups than in the glucose groups. Liver GSH reductase (GSH-Red) activity was lower in the -Zn-fructose group than in its control group. Liver glutamine synthetase activity was lower in the -Zn-glucose group and in the fructose groups than in the glucose control group. Liver thiobarbituric acid reactive substance (TBARS) production was similar among the groups. Collectively, these results support the concept that Zn deficiency can result in an impaired oxidant defense system. Based on the observation that pair-fed control animals also showed evidence of oxidative damage, we suggest that one factor that contributes to the effect of Zn deficiency is the reduction in caloric intake that occurs in these animals. Fructose feeding resulted in increased activities of several of the oxidant defense enzymes. Protein oxidative damage assessed by glutamine synthetase activity was increased by both Zn deficiency and fructose feeding.     

Downregulation of NADPH oxidase, antioxidant enzymes, and inflammatory markers in the heart of streptozotocin-induced diabetic rats by N-acetyl-L-cysteine

We investigated the effect of N-acetyl-l-cysteine (NAC) on the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, antioxidant enzymes, and inflammatory markers in diabetic rat hearts. Metabolic parameters, free 15-F(2t)-isoprostane level, protein expression of NADPH oxidase, superoxide dismutase (SOD), heme oxygenase (HO-1), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) were analyzed in control and streptozotocin-induced diabetic rats treated with or without NAC in drinking water for 8 wk. The cardiac protein expression of p67(phox) and p22(phox) was increased in diabetic rats, accompanied by increased NADPH-dependent superoxide production. As a compensatory response to the increased NADPH oxidase, the protein expression of Cu-Zn-SOD and HO-1 and the total SOD activity were also increased in diabetic rat hearts. Consequently, cardiac free 15-F(2t)-isoprostane, an index of oxidative stress, was increased in diabetic rats, indicating that the production of reactive oxygen species becomes excessive in diabetic rat hearts. Cardiac inflammatory markers IL-6 and COX-2 were also increased in diabetic rats. NAC treatment prevented the increased expression of p22(phox) and translocation of p67(phox) to the membrane in diabetic rat hearts. Subsequently, the levels of cardiac free 15-F(2t)-isoprostane, HO-1, Cu-Zn-SOD, total SOD, IL-6, and COX-2 in diabetic rats were decreased by NAC. Consequently, cardiac hypertrophy was attenuated in diabetic rats treated with NAC. The protective effects of NAC on diabetic rat hearts may be attributable to its protection of hearts against oxidative damage induced by the increased NADPH oxidase and to its reduction in cardiac inflammatory mediators IL-6 and COX-2.     

Exogenous nitric oxide effect on fructan accumulation and FBEs expression in chilling-sensitive and chilling-resistant wheat

This study was to investigate the effect of exogenous nitric oxide (NO) on fructan accumulation and fructan biosynthesic enzymes (FBEs) expression in seedlings leaves of two wheat (Triticum aestivum L.) cultivars, winter wheat (Zhoumai18, ZM) and spring wheat (Yanzhan4110, YZ), under 4 °C. The seedlings of two wheat cultivars were subjected to different concentrations of sodium nitroprussiate (SNP) for 0, 24, 48, and 96 h. Relative water content (RWC) was increased by exogenous NO in YZ, but decreased in ZM. Except for glucose, fructose and fructans of degree of polymerization (DP) 3 in YZ, other soluble carbohydrates contents in the two wheat cultivars all increased to different degrees. The activities of FS (including sucrose: sucrose 1-fructosyltransferase (1-SST, EC: 2.4.1.99) and sucrose: fructan 6-fructosyltransferase (6-SFT, EC: 2.4.1.10)) were significantly higher than fructan: fructan 1-fructosyltransferase (1-FFT, EC: 2.4.1.100) in the seedlings of two wheat cultivars. The same phenomenon occurred to FBEs expression. In addition, sucrose content decreased while fructans content increased under low temperature, which was in accordance with the improved 1-FFT activity in ZM. Moreover, fructans content increased to a high level under high concentration of NO in ZM while kept at a constant low level in YZ. The expression levels of FBEs were universally higher in ZM than in YZ, which identified with the high frost resistance of the winter cultivar. It is concluded that exogenous NO treatment on wheat may be a good option to reduce chilling injury by regulating fructan accumulation in leaves. This is the first report owing that exogenous NO alleviated the negative effects of chilling stress by accumulating fructans in wheat.     

Impacts of high-sucrose diet on circadian rhythms in the small intestine of rats

Excessive sucrose intake, known as fructose toxicity, leads to fatty liver, hyperlipidemia, and metabolic syndrome. Circadian disorders also contribute to metabolic syndrome. Here, we investigated the effect of excessive sucrose intake on circadian rhythms of the small intestine, the main location of sucrose absorption, to elucidate a mechanism of sucrose-induced abnormal lipid metabolism. Male Wistar rats were fed control starch or high-sucrose diets for 4 weeks. High-sucrose diet-induced fatty liver and hypertriglyceridemia in rats. Amplitudes of PER1/2 expression oscillations in the small intestine were reduced by excessive sucrose, while gene expression of GLUT5 and gluconeogenic enzymes was enhanced. These changes would contribute to interfering in lipid homeostasis as well as adaptive responses to control fructose toxicity in rats.     

The effect on some enzymes of rat tissue of diets low in fat content

1. Rats of two strains were kept on three different diets; one was a commercial diet of rat pellets, one contained about 80% of sucrose and 20% of casein and was supplemented with corn oil, and the third was a similar diet without the corn oil. 2. On the commercial diet, the specific activities of pyruvate kinase, glucose 6-phosphate dehydrogenase and fructose 1,6-diphosphatase in the livers of one strain of rats (strain A) were 1.5-3 times those in the other strain (strain B). When the diet high in sucrose and supplemented with corn oil was given, there were large increases in the specific activity of pyruvate kinase, glucose 6-phosphate dehydrogenase and fructose 1,6-diphosphatase in the livers of strain A rats. With strain B rats the increases were much smaller. Omission of corn oil from the diet caused a threefold increase in the specific activity of glucose 6-phosphate dehydrogenase in strain B rats, but had little effect on other enzymes. 3. The enzymes of the kidneys and hearts of strain A rats were also more active than those of strain B rats. In strain A rats, the specific activities of pyruvate kinase and fructose 1,6-diphosphatase in the kidney increased when the sucrose content of the diet was high, but in the kidneys of strain B rats there was little change. 4. In strain A rats, the specific activity of pyruvate kinase in the heart more than doubled with the high-sucrose-corn oil diet and increased threefold when corn oil was omitted. No changes were seen in strain B rats. 5. In strain A rats, omission of corn oil from the diet increased the ability of the kidneys to synthesize glucose from lactate. 6. In strain B rats, addition of corn oil to the diet resulted in a decrease in the liver in the specific activity of ATP citrate lyase and in the ability to incorporate acetate into lipid.     

Ginger extract mitigates ethanol-induced changes of alpha and beta – myosin heavy chain isoforms gene expression and oxidative stress in the heart of male wistar rats

The association between ethanol consumption and heart abnormalities, such as chamber dilation, myocyte damage, ventricular hypertrophy, and hypertension is well known. However, underlying molecular mediators involved in ethanol-induced heart abnormalities remain elusive. The aim of this study was to investigate the effect of chronic ethanol exposure on alpha and beta – myosin heavy chain (MHC) isoforms gene expression transition and oxidative stress in rats’ heart. It was also planned to find out whether ginger extract mitigated the abnormalities induced by ethanol in rats’ heart. Male wistar rats were divided into three groups of eight animals as follows: Control, ethanol, and ginger extract treated ethanolic (GETE) groups. After six weeks of treatment, the results revealed a significant increase in the β-MHC gene expression, 8- OHdG amount, and NADPH oxidase level. Furthermore, a significant decrease in the ratio of α-MHC/β-MHC gene expression to the amount of paraoxonase enzyme in the ethanol group compared to the control group was found. The consumption of Ginger extract along with ethanol ameliorated the changes in MHC isoforms gene expression and reduced the elevated amount of 8-OHdG and NADPH oxidase. Moreover, compared to the consumption of ethanol alone, it increased the paraoxonase level significantly.These findings indicate that ethanol-induced heart abnormalities may in part be associated with MHC isoforms changes mediated by oxidative stress, and that these effects can be alleviated by using ginger extract as an antioxidant molecule.     

盐敏感性高血压大鼠eNOS、iNOS表达与心肌细胞凋亡关系分析

目的探讨盐敏感性高血压形成和心肌细胞损害产生的机制。方法以辣椒辣索损伤Wistar大鼠感觉神经,饲喂高盐饲料,建立盐敏感性高血压大鼠模型。苏木素～伊红染色观察大鼠组织病理学改变;分光光度法检测心肌组织iNOS活性和NO含量;免疫组织化学方法检测心肌eNOS、iNOS蛋白表达;RT．PCR检测心肌eNOS、iNOSmRNA的表达。单细胞凝胶电泳检测心肌细胞凋亡。结果实验结束时各组比较体重无显著性差异（P〉0．05）。在第2、3、4周时,辣椒辣素高盐组鼠尾收缩压与对照组相比差异显著（P〈0．05）。辣椒辣素高盐组心肌细胞排列紊乱、细胞间隙明显增大,细胞核排列不整齐;心肌iNOS、NO水平升高（P〈0．05）;eNOS蛋白表达减少（P〈0．05）与eNOSmRNA表达减少（P〈0．01）;iNOS蛋白表达和iNOSmRNA表达显著增高（P〈0．01）;凋亡细胞数升高（P〈0．05）。结论eNOSmRNA和蛋白的低表达与感觉神经损伤性盐敏感性高血压大鼠形成相关。iNOSmRNA和蛋白的高表达及iNOS活性升高使心肌组织局部产生大量NO。NO可能使得感觉神经损伤性盐敏感性高血压大鼠心肌细胞凋亡增加,从而加重心肌的损伤。     

Enhancement of sucrase-isomaltase gene expression induced by luminally administered fructose in rat jejunum

We have previously shown that feeding a diet containing sucrose to rats causes an elevation of sucrase-isomaltase (SI) mRNA level in the jejunum. In this study, we examined whether the SI mRNA level could be directly elevated by administration of one of the constituting monosaccharides (i.e., glucose and/or fructose). Gastric intubation of a sucrose solution caused increases in both sucrase activity and SI mRNA level in the jejunum. Intrajejunal intubation of fructose, but not glucose, led to an elevation of sucrase activity and SI mRNA level. To examine whether fructose directly affects the gene expression of SI at the segment where the absorption of this sugar takes place or the sugar-induced increase in the gene expression of SI is secondary to any possible changes in the level(s) of certain hormonal factor(s) in the blood stream, a solution containing either fructose or glucose was simultaneously perfused into two consecutive cannulated and irrigated loops of jejunum that were not isolated from blood circulation. Compared with the loop perfused with glucose, the loop perfused with fructose exhibited significantly greater sucrase activity and SI mRNA level as well as the elevated GLUT5 mRNA level. These results suggest that fructose is capable of directly increasing the gene expression of SI and GLUT5 in the confined segment where fructose is absorbed.     

Tempol attenuates atherosclerosis associated with metabolic syndrome via decreased vascular inflammation and NADPH-2 oxidase expression

Abstract

Oxidative stress is an important factor in the generation of vascular injury in atherosclerosis. Chronic administration of fructose in rodents is able to facilitate oxidative damage. In the present study we evaluated the role of Tempol, a superoxide dismutase mimetic, on the effect of high fructose intake in apolipoprotein E-deficient (ApoE-KO) mice. Rodents were fed with fructose overload (FF, 10% w/v) for 8 weeks and treated with Tempol 1 mg/kg/day the latest 4 weeks. Tempol revert the pro-oxidant effects caused by FF, diminished lipid peroxidation and impaired vascular NADPH oxidase system through the downregulation of p47phox expression in the vascular wall. Tempol inhibited the expression of vascular adhesion molecule 1 (VCAM-1) in aorta and reduced the development of atheroma plaques. Our results indicate that tempol attenuates oxidative stress by interfering with the correct assembly of Nox2 oxidase complex in the vascular wall and is able to reduce atherosclerosis. Thus tempol represents a potential therapeutic target for preventing risk factors associated with metabolic syndrome.     

Diet-induced adaptation of intestinal fructose absorption in the rat.

The effect of dietary sucrose, fructose and glucose on the intestinal absorption of fructose and glucose was investigated in adult rats in vivo: Glucose absorption was not affected by the type of dietary carbohydrate, while the absorption of fructose was increased by the ingestion of the sucrose or fructose diet, as compared with the glucose diet. An almost maximal increase of fructose absorption was already observed when the quarter of the total dietary carbohydrates was replaced by fructose. Faecal fructose elimination declined during the feeding experiment. The enhanced intestinal absorption of the fructose load in rats fed the fructose diet was manifested by higher concentrations of fructose, but also of glucose and lactate in the hepatic portal blood.     

Effects of dietary calcium restriction and acute exercise on the antioxidant enzyme system and oxidative stress in rat diaphragm

Calcium deficiency is considered to increase intracellular calcium level; thus the aim of the current study was to elucidate whether dietary calcium restriction enhanced exercise-induced oxidative stress in rat diaphragm. Twenty male Wistar rats were randomly assigned to either a control group or a group subjected to 1 mo of calcium restriction. In addition, each group was subsequently subdivided into rested or acutely exercised group. Dietary calcium restriction significantly (P < 0.05) upregulated the activities of manganese-superoxide dismutase (Mn-SOD), copper-zinc-superoxide dismutase (Cu-Zn-SOD), and glutathione peroxidase (Gpx) but not catalase. Acute exercise, in addition to calcium restriction, decreased both SOD isoenzymes in the diaphragm of calcium-restricted rats (P < 0.05). On the other hand, calcium restriction resulted in increased Gpx mRNA expression (P < 0.05). In control rats, acute exercise significantly (P < 0.05) increased the expressions of both SOD mRNAs, whereas in the calcium-restricted rats, it increased that of Mn-SOD mRNA (P < 0.05) but decreased that of Gpx mRNA (P < 0.05). Furthermore, reactive carbonyl derivative, a marker of protein oxidation, was significantly greater in the calcium-restricted rats than in the control rats after acute exercise (P < 0.05). The results suggest that antioxidant enzymes in rat diaphragm were upregulated in response to an increased oxidative stress by dietary calcium restriction but that upregulation is not enough to cope with exercise-induced further increase of oxidative stress.     

17β-雌二醇对去卵巢胰岛素抵抗大鼠主动脉舒缩功能损伤的保护作用

为观察17β-雌二醇（17beta-estradiol,17β-E2）对去卵巢胰岛素抵抗（insulin resistance,IR）大鼠主动脉结构和舒缩功能的影响及其可能机制,成年雌性Sprague-Dawley大鼠卵巢切除后,高果糖喂养8周诱导IR,同时给予生理剂量的17β-E2（30μg／kg）,每天皮下注射一次,并检测IR相关指标。大鼠胸主动脉石蜡切片,HE染色,图像分析系统测定其结构。采用血管环灌流法,观察各组大鼠胸主动脉环对新福林（L-phenylephrine,PE）的收缩反应和对ACh、硝普钠（sodium nitroprusside,SNP）的舒张反应以及一氧化氮合酶（nitric oxide synthase,NOS）抑制剂N-硝基-L-精氨酸甲脂（N-nitrl-L-arginine methylester,L-NAME）对卵巢切除＋果糖喂养＋17β-E2组大鼠胸主动脉ACh的舒张反应的影响;检测各组大鼠一氧化氮（nitric oxide,NO）含量。结果显示：（1）17β-E2能防止高果糖诱导的去卵巢IR人鼠收缩压升高、高胰岛素血症和胰岛素敏感性下降;（2）各组火鼠胸主动脉的结构无显著性差异;（3）卵巢切除＋果糖喂养组大鼠与卵巢切除组或果糖喂养组相比,血清NO显著降低,胸主动脉对PE的收缩反应显著增强,对ACh的舒张反应显著降低,17β-E2能逆转上述改变,L-NAME可部分阻断17β-E2的这种作用;（4）各组大鼠胸主动脉对SNP的舒张反应和去内皮后对PE的收缩反应均无显著差异。以上结果表明,17β-E2能抑制高果糖诱导的去卵巢IR大鼠血管舒缩功能的紊乱,其机制一方面可能是部分通过血管内皮细胞NOS途径促进NO的释放,保护内皮细胞;另一方面可能是通过降低血压,血清胰岛素水平,改善IR所致。     

左卡尼汀对血液透析肾性贫血的疗效及氧化应激的影响

目的:探讨左卡尼汀联合蔗糖铁对血液透析肾性贫血患者的疗效及氧化应激的影响。方法:收取2013年3月至2015年6月间于我院进行维持性血液透析的肾性贫血患者76例作为研究对象均分为观察组及对照组,分别给予左卡尼汀联合蔗糖铁治疗或单用蔗糖铁治疗。对两组患者临床疗效、贫血及铁代谢指标、氧化应激水平以及不良反应发生率进行考察与比较。结果:观察组治疗总有效率高于对照组(P0.05)。治疗后两组患者贫血及铁代谢指标均明显升高,观察组明显高于对照组(P0.05)。治疗后对照组患者MDA、AOPP,观察组患者SOD、GSH-Px明显升高,组间差异有统计学意义(P0.05)。两组患者不良反应发生率无显著差异(P0.05)。结论:左卡尼汀联合蔗糖铁对维持性血液透析肾性贫血患者具有良好的治疗效果,安全性高,可有效降低氧化应激水平。     

Response of hepatic fructokinase to long-term sucrose diets and diabetes in spiny mice, albino mice and rats

The activity of hepatic fructokinase increased about 2-fold in desert-derived spiny mice (Acomys cahirinus) and laboratory bred albino mice and rats, maintained on a 50% sucrose diet for 3 months. The role of fructose as the specific inducer was apparent, as 25% fructose diet produced activity increases similar to those of sucrose in contrast to 25% glucose diet. The activity of hexokinase was not affected by the sucrose diet, that of glucokinase rose marginally but those of pyruvate kinase and NADP-malate dehydrogenase rose pronouncedly, especially in the spiny mice. Fructokinase activity increased significantly only after 2 weeks on the diet and continued to rise gradually. The activities of other gycolytic enzymes rose markedly already after 3 days and peaked at about 14 days. Fasting for 48 hr did not influence fructokinase activity while markedly reducing that of glucokinase, pyruvate kinase and NADP-malate dehydrogenase. Streptozotocin diabetes in rats resulted in a 40% reduction in fructokinase activity after 14 days which was restored after 6 days of insulin treatment. The activity increases of other glycolytic enzymes were more marked. However, the fructokinase induction on the sucrose diet was evident also in diabetic rats, suggesting that the insulin and substrate effects are independent. The preference of fructose over glucose phosphorylation capacity was clearly demonstrable in the non-diabetic and diabetic rats and became enhanced on sucrose feeding. The activity of triokinase also increased on the sucrose diet in the 3 rodent species, suggesting a coordinative substrate effect on the induction of these two rate-limiting fructolysis enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a selective endothelin a receptor antagonist on the expressions of iNOS and eNOS in the heart of early streptozotocin-induced diabetic rats

Vascular tone is regulated through the actions of locally produced agents. Among the vasoconstrictors, the most potent agent is endothelin (ET), which exerts its vasoconstrictor actions principally through ET type A (ET(A)) receptors. Of the vasodilators, nitric oxide (NO) seems to be the most important contributor to the acute regulation of vascular tone. Vasculopathy is an important feature of diabetes mellitus (DM). Endogenous ET-mediated vasoconstrictor tone is augmented in diabetic states, and conflicting results persist concerning the NO system in diabetes. The present study investigated the expressions of inducible NO synthases (iNOS) and endothelial NOS (eNOS) in the heart of diabetic animals and the effects of a selective ET(A) receptor antagonist on these alterations. Type I diabetes was induced by intraperitoneal injection of streptozotocin (65 mg/kg) in Sprague-Dawley rats, while control (Con) rats received only citrate buffer. After 1 week, the streptozotocin-administered rats were randomly divided into two groups: the selective ET(A) receptor antagonist-administered group (DM+TA-0201, 1 mg/kg/day, by osmotic minipump for 2 weeks) and the DM+vehicle group (comprising the diabetic rats that received saline). The random blood glucose level was 405 +/- 103 mg/dl in DM animals, and this level was unchanged by ET antagonism. Body weight was more greatly decreased in DM rats than in Con rats, but the left ventricle to body weight ratio was increased in the DM group and was unaffected by ET antagonism. Protein expressions of eNOS and iNOS were assessed in the left ventricular tissues. eNOS expression was significantly increased in DM heart and was greatly inhibited by the treatment with ET antagonist. The expression of iNOS was also increased in early DM heart but was reversed by the ET antagonist. Thus, endothelin antagonism might be beneficial for DM heart by reversing the upregulated eNOS and iNOS expressions.     

茶多酚对NASH 大鼠肝脏组织VEGF 及氧化应激的影响

目的:茶多酚对NASH大鼠肝脏组织VEGF及氧化应激的影响。方法:雄性SD大鼠30只,随机分为3组,正常对照组、模型组、茶多酚治疗组。正常组普通饲料喂养,模型组喂高脂饮食,茶多酚治疗组在高脂饮食12周后茶多酚(150mg(/kg.d)灌胃治疗,16周末处死各组大鼠,留取肝脏组织,观察各组大鼠肝组织病理改变,测定其肝脏丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性以及血管内皮生长因子(VEGF)、Ⅰ、Ⅲ型胶原的表达。结果:模型组大鼠肝组织中SOD活性降低而MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达均明显高于正常组。茶多酚治疗可减轻肝纤维化程度,显著升高肝组织中SOD活性、降低MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达水平。结论:茶多酚可通过抑制肝纤维化组织VEGF表达,降低肝组织氧化应激水平而发挥抗肝纤维化作用。     

Introduction of Daytime Feeding in Rats by Exposure to Choice of a Sugar Diet

Food intakes of rats having first access to either sucrose or fructose as the carbohydrate source in a three-way selection of macronutrients were compared. In the first period of choice between sugar, protein and fat similar day/night intakes were found in rats given sucrose or fructose. When rats had a first experience with either sucrose or fructose as the carbohydrate source, their total energy and macronutrient intakes decreased dramatically and diurnal rather than nocturnal feeding occurred when sugar was switched. These findings indicate that a previous adaptation to a sugar as a carbohydrate source in a three-way selection design has long-lasting effects on the subsequent pattern and amount of food intake on a similar choice among diets.     

Sinapic Acid Prevents Hypertension and Cardiovascular Remodeling in Pharmacological Model of Nitric Oxide Inhibited Rats

Objectives

Hypertensive heart disease is a constellation of abnormalities that includes cardiac fibrosis in response to elevated blood pressure, systolic and diastolic dysfunction. The present study was undertaken to examine the effect of sinapic acid on high blood pressure and cardiovascular remodeling.

Methods

An experimental hypertensive animal model was induced by L-NAME intake on rats. Sinapic acid (SA) was orally administered at a dose of 10, 20 and 40 mg/kg body weight (b.w.). Blood pressure was measured by tail cuff plethysmography system. Cardiac and vascular function was evaluated by Langendorff isolated heart system and organ bath studies, respectively. Fibrotic remodeling of heart and aorta was assessed by histopathologic analyses. Oxidative stress was measured by biochemical assays. mRNA and protein expressions were assessed by RT-qPCR and western blot, respectively. In order to confirm the protective role of SA on endothelial cells through its antioxidant property, we have utilized the in vitro model of H₂O₂-induced oxidative stress in EA.hy926 endothelial cells.

Results

Rats with hypertension showed elevated blood pressure, declined myocardial performance associated with myocardial hypertrophy and fibrosis, diminished vascular response, nitric oxide (NO) metabolites level, elevated markers of oxidative stress (TBARS, LOOH), ACE activity, depleted antioxidant system (SOD, CAT, GPx, reduced GSH), aberrant expression of TGF-β, β-MHC, eNOS mRNAs and eNOS protein. Remarkably, SA attenuated high blood pressure, myocardial, vascular dysfunction, cardiac fibrosis, oxidative stress and ACE activity. Level of NO metabolites, antioxidant system, and altered gene expression were also repaired by SA treatment. Results of in vitro study showed that, SA protects endothelial cells from oxidative stress and enhance the production of NO in a concentration dependent manner.

Conclusions

Taken together, these results suggest that SA may have beneficial role in the treatment of hypertensive heart disease by attenuating fibrosis and oxidative stress through its antioxidant potential.