Resveratrol treatment improves the altered metabolism and related dysbiosis of gut programed by prenatal high-fat diet and postnatal high-fat diet exposure

A maternal high-fat (HF) diet sensitizes offspring to the adverse effects of postnatal HF intake and can lead to metabolic dysregulation. Resveratrol, a natural polyphenolic compound found in grapes and red wine, could help to relieve metabolic syndrome dysregulation. Since the gut microbiota is known to be closely related to metabolic homeostasis, this study aimed to investigate the impact of a combination of maternal and postweaning HF diets on the gut microbiota and whether resveratrol could relieve the gut dysbiosis associated with metabolic dysregulation. Sprague–Dawley dams were sustained on either a chow or HF diet before mating, during pregnancy and during lactation. Their offspring were randomly fed chow or a HF diet after weaning. Four experimental groups were generated: CC (maternal/postnatal chow diet), HC (maternal HF/postnatal chow diet), CH (maternal chow/postnatal high-fat diet) and HH (maternal/postnatal HF diet). A fifth group consisted of HH with resveratrol treatment. We found that both maternal and postnatal HF exposure has a distinct effect on the gut microbiota metagenome of offspring. Maternal HF diet exposure decreased plasma acetate, propionate and butyrate level, while postnatal HF diet exposure decreased plasma acetate level in adult life. The metabolic dysregulation programed by the maternal and postnatal HF diets was related to the relevant gut microbiota. Resveratrol treatment ameliorated the altered plasma propionate level related to maternal HF and postnatal HF diet treatment. Resveratrol treatment also improved most of the altered metabolic dysregulation and related dysbiosis programmed by maternal and postnatal HF diet exposure.     

Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis

Resveratrol is a natural polyphenol that has been reported to reduce the risk of obesity and nonalcoholic fatty liver disease (NAFLD). Recent evidence has demonstrated that the gut microbiota plays an important role in the protection against NAFLD and other metabolic diseases. The present study aimed to investigate the relationship between the gut microbiota and the beneficial effects of resveratrol on the amelioration of NAFLD in mice. We observed marked decreases in body weight and liver steatosis and improved insulin resistance in high-fat diet (HFD)-fed mice treated with resveratrol. Furthermore, we found that resveratrol treatment alleviated NAFLD in HFD-fed mice by improving the intestinal microenvironment, including gut barrier function and gut microbiota composition. On the one hand, resveratrol improved gut intestinal barrier integrity through the repair of intestinal mucosal morphology and increased the expression of physical barrier- and physiochemical barrier-related factors in HFD-fed mice. On the other hand, in HFD-fed mice, resveratrol supplementation modulated the gut bacterial composition. The resveratrol-induced gut microbiota was characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group and Alistipes, as well as an increased abundance of short-chain fatty acid (SCFA)-producing bacteria, such as Allobaculum, Bacteroides and Blautia. Moreover, transplantation of the HFDR-microbiota into HFD-fed mice sufficiently decreased body weight, liver steatosis and low-grade inflammation and improved hepatic lipid metabolism. Collectively, resveratrol would provide a potentially dietary intervention strategy against NAFLD through modulating the intestinal microenvironment.     

Resveratrol attenuates oxidative stress and prevents steatosis and hypertension in obese rats programmed by early weaning

We hypothesized that resveratrol, a natural phytoalexin found in grapes, can prevent oxidative stress, obesity and its related disturbances in obese rats programmed by early weaning. Lactating Wistar rats were separated into two groups: early weaning (EW) — dams who were wrapped with a bandage to interrupt the lactation in the last 3 days of lactation; control — dams whose pups had free access to milk during all lactation. At the 150th day, EW offspring were randomly subdivided into EW+resveratrol (EW+Res) — resveratrol (30 mg/kg/day); EW+vehicle (EW) — rats that received 0.5% (w/v) aqueous methylcellulose. The control group received vehicle. Rats were treated by gavage daily for 30 days. EW offspring developed hyperphagia, higher body weight, visceral obesity, higher systolic (SBP) and diastolic blood pressure (DBP) (+15% and +20%, respectively; P<.05) and higher serum triglycerides (TG) and low-density lipoprotein but lower high-density lipoprotein (+55%, +33% and ?13%, respectively; P<.05). Resveratrol normalized food intake, SBP and DBP and prevented obesity and dyslipidemia in EW+Res. EW rats had higher plasma and liver thiobarbituric-acid-reactive substances (TBARS) and lower plasma superoxide dismutase (SOD) and liver glutathione peroxidase activities (+51%, +18%, ?58%, ?31%, respectively; P<.05), and resveratrol normalized both plasma and liver TBARS and increased the activity of SOD and catalase in plasma. EW rats presented liver steatosis and higher liver TG, and resveratrol prevented these hepatic alterations. In conclusion, this study demonstrated a potential therapeutic use of resveratrol in preventing obesity and oxidative stress and reducing the risk of hypertension, dyslipidemia and steatosis in adult rats programmed by early weaning.     

Focus: The Science of Stress: Resveratrol Supplants Captopril’s Protective Effect on Cardiac Remodeling in a Hypertension Model Elicited by Renal Artery Stenosis

Background: Renovascular hypertension elicits cardiac damage and remodeling. Two-kidney, one-clip (2K1C) is an experimental model used to study hypertension pathophysiology. In this model, the renin-angiotensin-system (RAS) is overactive due to renal artery stenosis, leading to cardiac remodeling. Redox mechanisms underlying RAS activation mediate hypertension-induced cardiovascular damage. Preclinical studies and clinical trials demonstrated resveratrol’s protective effects in cardiovascular diseases, mainly attributed to its antioxidant properties. We hypothesized resveratrol alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor would be beneficial against cardiac damage caused by renovascular hypertension. Objective: We investigated the benefits of resveratrol against cardiac remodeling in 2K1C rats compared with captopril. Methods: Male Wistar rats underwent unilateral renal stenosis – 2K1C Goldblatt model of hypertension. Systolic Blood Pressure (SBP) was measured before and 6 weeks after surgery. Hypertensive 2K1C rats presented SBP≥160 mmHg. From the 6^th week after the surgery, the animals received oral resveratrol (20 mg/kg), captopril (12 mg/kg), or their combination for 3 times per week for 3 weeks. Whole heart hypertrophy was evaluated. Histological assays assessed left ventricle hypertrophy and fibrosis. Results: Renovascular hypertension caused cardiac hypertrophy, accompanied by increased myocyte diameter and collagen deposition. Resveratrol reduced 2K1C rats’ SBP and whole heart hypertrophy, independently of captopril. Resveratrol caused a higher reduction in ventricular hypertrophy than captopril. Collagen deposition was greater reduced by 2K1C treated only with resveratrol than with captopril alone or combined with resveratrol. Conclusion: Independent of captopril, resveratrol prompts cardioprotective effects on cardiomyocyte remodeling and fibrosis resulting from renovascular hypertension in 2K1C rats.     

肠道菌群及其代谢产物氧化三甲胺——冠心病治疗的新靶点

冠心病 (Coronary artery disease,CAD) 是全球发病率和死亡率最高的一种心血管疾病,冠心病和肠道菌群失调密切相关,肠道菌群可能是未来冠心病的重要诊断标志物,改善肠道菌群微环境有望成为治疗冠心病的新途径。作为肠道菌群参与合成的活性代谢产物,氧化三甲胺 (Trimethylamine-N-oxide,TMAO) 水平的升高与心血管疾病患病风险、全因死亡率的增加有关;基础研究表明TMAO可能具有促动脉粥样硬化特性;这些研究提示TMAO可作为预防和治疗冠心病的潜在靶点。文中分析了当前调控肠道菌群及其代谢产物TMAO治疗冠心病的临床及基础性研究,以期为冠心病的治疗提供帮助。     

Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity

Background  

Resveratrol, a natural polyphenolic compound, was shown to protect rodents against high-fat-diet induced diabesity by boosting energy metabolism. To the best of our knowledge, no data is yet available on the effects of resveratrol in non-human primates. Six non-human heterotherm primates (grey mouse lemurs, Microcebus murinus) were studied during four weeks of dietary supplementation with resveratrol (200 mg/kg/day) during their winter body-mass gain period. Body mass, spontaneous energy intake, resting metabolic rate, spontaneous locomotor activity and daily variations in body temperature were measured. In addition, the plasma levels of several gut hormones involved in satiety control were evaluated.     

Transient Exposure of Enalapril Normalizes Prenatal Programming of Hypertension and Urinary Angiotensinogen Excretion

Maternal low protein diet programs offspring to develop hypertension as adults. Transient exposure to angiotensin converting enzyme inhibitors or angiotensin II receptor blockers can result in improvement in hypertension. Male rats whose mothers received a low protein diet during the last half of pregnancy were given either vehicle, continuous enalapril (CE) in their drinking water or were given transient enalapril exposure (TE) after weaning at 21 days of age. The TE group had enalapril in their drinking water for 21 days starting from day 21 of life. All rats were studied at 6 months of age. Vehicle treated rats whose mothers were fed a low protein diet were hypertensive, had albuminuria, and demonstrated upregulation of the intrarenal renin-angiotensin system as evidenced by higher urinary angiotensinogen and urinary angiotensin II levels. In low protein rats both continuous and transient exposure to enalapril normalized blood pressure, urinary angiotensinogen and urinary angiotensin II levels at 6 months of age, but only continuous administration of enalapril decreased urinary albumin excretion. These data support the importance of the intrarenal renin-angiotensin system in mediating hypertension in programmed rats and transient exposure to enalapril can reprogram the hypertension and dysregulation of the intrarenal renin-angiotensin system.     

Postnatal high-fat diet sex-specifically exacerbates prenatal dexamethasone-induced hypertension: Mass spectrometry-based quantitative proteomic approach

Hypertension can originate from pre- and post-natal insults. High-fat (HF) diet and prenatal dexamethasone (DEX) exposure are both involved in hypertension of developmental origins. We examined whether postnatal HF diet sex-specifically increases the vulnerability to prenatal DEX exposure-induced programmed hypertension in adult offspring. Additionally, we sought to identify candidate proteins involved in programmed hypertension through a mass spectrometry-based quantitative proteomic approach. Male and female offspring were studied separately: control, DEX, HF, and DEX + HF (n=8/group). Pregnant Sprague–Dawley rats received dexamethasone (0.1 mg/kg body weight) or vesicle from gestational day 16–22. Offspring received high-fat diet (D12331, Research Diets) or regular diet from weaning to 4 months of age. Rats were sacrificed at 4 months of age. We found that postnatal HF diet increased vulnerability of prenatal DEX-induced hypertension in male but not in female adult offspring. Additionally, HF and DEX elicited renal programming in a sex-specific fashion. In males, DEX + HF increased renal parvalbumin (PVALB) and carbonic anhydrase III (CA III) protein levels. While prenatal DEX down-regulated PVALB and CA III protein abundance in female offspring kidneys. Moreover, DEX + HF increased renal protein level of type 3 sodium hydrogen exchanger (NHE3) in males but not in females. In conclusion, postnatal HF diet and prenatal DEX exposure synergistically induced programmed hypertension in male-only offspring. DEX + HF induced sex-specific alterations of protein profiles in offspring kidneys. By identifying candidate proteins underlying sex-specific mechanisms, our results could lead to novel offspring sex-specific interventions to prevent hypertension induced by antenatal corticosteroids and postnatal HF intake in both sexes.     

白藜芦醇抑制嗜水气单胞菌毒力作用研究

为探索白藜芦醇(Resveratrol, Res)在水产动物细菌病防控中的应用价值, 实验以淡水养殖中重要的细菌病原嗜水气单胞菌(Aeromonas hydrophila)为研究对象, 通过设置药物浓度梯度, 检测其对嗜水气单胞菌生长、生物膜形成和溶血活性的抑制作用, 和对毒力及群感调控系统相关基因表达的影响; 同时通过人工感染异育银鲫(Carassius auratus gibelio)试验检测其对鱼体保护作用和对鱼体炎症相关因子基因表达的影响。结果显示: 白藜芦醇对嗜水气单胞菌的最小抑菌浓度(MIC)>1024 μg/mL; 浓度低于64 μg/mL时, 对菌株生长影响不显著; 浓度≥32 μg/mL时, 对病原菌株生物膜形成和溶血活性具有显著抑制作用(P<0.05), 且随剂量增加而增强。荧光定量RT-PCR结果分析发现白藜芦醇能引起嗜水气单胞菌群感调控系统中luxR和luxS基因分别显著上调和下调表达; 外膜蛋白基因omp表达显著下降。人工感染试验发现攻毒前两小时腹腔注射25、50和100 mg/kg白藜芦醇处理组的异育银鲫死亡率显著下降, 鱼体炎症相关的肿瘤坏死因子(TNF-α)和Ⅱ型干扰素(IFN-γ)的mRNA表达量也显著下降。研究表明药用植物大黄、虎杖等所含白藜芦醇成分能有效抑制嗜水气单胞菌毒力, 降低鱼体炎症反应的功效; 腹腔注射25—100 mg/kg白藜芦醇对感染病原菌的异育银鲫有一定保护作用。     

Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations

The dietary polyphenolic compound resveratrol, by activating the protein deacetylase enzyme silent information regulator 2/sirtuin 1 (SIRT1), prolongs life span in evolutionarily distant organisms and may mimic the cytoprotective effects of dietary restriction. The present study was designed to elucidate the effects of resveratrol on cigarette smoke-induced vascular oxidative stress and inflammation, which is a clinically highly relevant model of accelerated vascular aging. Cigarette smoke exposure of rats impaired the acetylcholine-induced relaxation of carotid arteries, which could be prevented by resveratrol treatment. Smoking and in vitro treatment with cigarette smoke extract (CSE) increased reactive oxygen species production in rat arteries and cultured coronary arterial endothelial cells (CAECs), respectively, which was attenuated by resveratrol treatment. The smoking-induced upregulation of inflammatory markers (ICAM-1, inducible nitric oxide synthase, IL-6, and TNF-alpha) in rat arteries was also abrogated by resveratrol treatment. Resveratrol also inhibited CSE-induced NF-kappaB activation and inflammatory gene expression in CAECs. In CAECs, the aforementioned protective effects of resveratrol were abolished by knockdown of SIRT1, whereas the overexpression of SIRT1 mimicked the effects of resveratrol. Resveratrol treatment of rats protected aortic endothelial cells against cigarette smoking-induced apoptotic cell death. Resveratrol also exerted antiapoptotic effects in CSE-treated CAECs, which could be abrogated by knockdown of SIRT1. Resveratrol treatment also attenuated CSE-induced DNA damage in CAECs (comet assay). Thus resveratrol and SIRT1 exert antioxidant, anti-inflammatory, and antiapoptotic effects, which protect the endothelial cells against the adverse effects of cigarette smoking-induced oxidative stress. The vasoprotective effects of resveratrol will likely contribute to its antiaging action in mammals and may be especially beneficial in pathophysiological conditions associated with accelerated vascular aging.     

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.     

Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms

Animal models support human epidemiological studies in demonstrating a relationship between impaired fetal growth and risk of adult hypertension. Undernutrition during pregnancy exerts programming effects on the developing kidney, and modulation of angiotensin receptor (ATR) expression has been observed persisting into adult life. Fetal overexposure to glucocorticoids is thought to be central to the nutritional programming of blood pressure and may act through an interaction with ATR expression. Pregnant female Wistar rats were fed a control (n = 6) or a maternal low-protein diet (MLP; n = 17) throughout pregnancy. The glucocorticoid dependency of MLP effects was tested using metyrapone, an inhibitor of corticosterone synthesis. MLP-fed rats were injected twice daily with metyrapone, metyrapone plus corticosterone, or vehicle over days 1-14 of pregnancy. At delivery, all animals were fed standard laboratory chow. MLP-exposed offspring 4 wk of age exhibited increased systolic blood pressure compared with controls (P < 0.05), which proved to be glucocorticoid dependent in males only. AT(1)R mRNA expression was independent of in utero dietary treatment. AT(2)R mRNA expression was downregulated in MLP-exposed females only (P < 0.05) and in a glucocorticoid-independent manner. Male offspring exhibited glucocorticoid-dependent hypertension with no modulation of renal ATR mRNA expression. In contrast, female offspring exhibited glucocorticoid-independent hypertension associated with reduced expression of renal AT(2)R mRNA. These data do not support the hypothesis that an interaction between glucocorticoid and ATR mRNA expression underlies the nutritional programming of blood pressure but instead suggest two independent mechanisms acting in a sex-specific manner.     

Resveratrol and 4-hydroxynonenal act in concert to increase glutamate cysteine ligase expression and glutathione in human bronchial epithelial cells

Resveratrol has been shown to protect against oxidative stress through modulating antioxidant capacity. In this study, we investigated resveratrol-mediated induction of glutathione (GSH) and glutamate cysteine ligase (GCL), and the combined effect of resveratrol and 4-hydroxynonenal (HNE) on GSH synthesis in cultured HBE1 human bronchial epithelial cells. Resveratrol increased GSH and the mRNA contents of both the catalytic (GCLC) and modulatory subunit (GCLM) of GCL. Combined HNE and resveratrol treatment increased GSH content and GCL mRNAs to a greater extent than either compound did alone. Compared to individual agent, combining exposure to HNE and resveratrol also showed more protection against cell death caused by oxidative stress. These effects of combined exposure were additive rather than synergistic. In addition, Nrf2 silencing significantly decreased the combined effect of HNE and resveratrol on GCL induction. Our data suggest that resveratrol increases GSH and GCL gene expression and that there is an additive effect on GSH synthesis between resveratrol and HNE. The results also reveal that Nrf2-EpRE signaling was involved in the combined effects.     

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.     

Impacts of ceftriaxone exposure during pregnancy on maternal gut and placental microbiota and its influence on maternal and offspring immunity in mice

This study aimed to investigate the association between microbiota found in the maternal gut and placenta, and whether ceftriaxone exposure during pregnancy could alter these microbiota, and consequently affect the immunity of the mothers and their offspring. The microbiota in the feces and placenta of the dams were comprehensively analyzed using16S rRNA sequencing. Furthermore, viable bacteria in the placentas and blood of pups were also isolated by plate cultivation then taxonomically identified in detail by clone sequencing. Serum cytokines collected from dams and pups were quantitatively profiled using Luminex. The spleen organ index of dams was significantly lower and the offspring serum interleukin-6 levels were significantly higher in ceftriaxone-treated mice compared with the control group. The maternal fecal microbiota community was drastically altered in ceftriaxone-treated mice with significantly decreased diversity, depletion of Bacteroidetes and the blooming of Tenericutes. However, the placenta microbiota was dominated by Proteobacteria especially characteristically by Ralstonia, which was distinct from the maternal gut microbiota, regardless of whether ceftriaxone treatment or not. Viable bacteria have been found in placenta and blood cultures. These results indicated that ceftriaxone exposure in pregnancy could dramatically alter maternal intestinal microbiota, which affected the immunity of the mothers and their offspring at least partly, characteristically by enhanced pro-inflammatory responses. This study also indicated that the placenta might harbor its own microbes and the microbes were distinct from maternal gut microbiota, which may not be affected by oral administration of ceftriaxone during pregnancy.     

Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses

Scavenging or quenching of the reactive oxygen species (ROS) involved in oxidative stress has been the subject of many recent studies. Resveratrol, found in various natural food products, has been linked to decreased coronary artery disease and preventing cancer development. The present study measured the effect of resveratrol on several different systems involving the hydroxyl, superoxide, metal/enzymatic-induced, and cellular generated radicals. The rate constant for reaction of resveratrol with the hydroxyl radical was determined, and resveratrol was found to be an effective scavenger of hydroxyl, superoxide, and metal-induced radicals as well as showing antioxidant abilities in cells producing ROS. Resveratrol exhibits a protective effect against lipid peroxidation in cell membranes and DNA damage caused by ROS. Resveratrol was also found to have a significant inhibitory effect on the NF-kappaB signaling pathway after cellular exposure to metal-induced radicals. It was concluded that resveratrol in foods plays an important antioxidant role.     

Resveratrol attenuates angiotensin II-induced senescence of vascular smooth muscle cells

Resveratrol (3,5,4'-trihydroxystilbene), a polyphenol abundant in red wine, is known to extend the life span of diverse species. On the contrary, it was reported that angiotensin (Ang) II enhances senescence of vascular smooth muscle cells (VSMCs). We, therefore, examined whether resveratrol attenuates Ang II-induced senescence of VSMC. Senescence-associated β-galactosidase (SA β-gal) assay showed that Ang II induced senescence of VSMC. The Ang II-induced senescence was inhibited by losartan, an Ang II type 1 receptor (AT1R) antagonist but not by PD123319, Ang II type 2 receptor antagonist, indicating that AT1R is responsible for the induction of senescence. Resveratrol suppressed Ang II-induced senescence of VSMC in a dose-dependent manner. In addition, resveratrol suppressed Ang II-induced induction of p53 and its downstream target gene p21, both of which play an important role in the induction of senescence. Resveratrol suppressed senescence of VSMC possibly through inhibition of AT1R-dependent induction of p53/p21. Suppression of p53 induction may be involved in the longevity by resveratrol.     

Piceatannol is more effective than resveratrol in restoring endothelial cell dimethylarginine dimethylaminohydrolase expression and activity after high-glucose oxidative stress

Glucose-induced oxidative stress is involved in endothelial dysfunction. Dimethylarginine dimethylaminohydrolase (DDAH) and arginase are regulators of the endothelial NO synthase (eNOS). This study aimed to compare the effect of two polyphenolic antioxidants, resveratrol and piceatannol, on DDAH and arginase pathways in bovine aortic endothelial cells under 25 mM glucose for 24 h. DDAH activity and expression were decreased in these cells as compared to control cells, whereas arginase activity was unchanged. DDAH inhibition led to intracellular accumulation of asymmetric dimethylarginine (ADMA), a natural inhibitor of eNOS. Under these conditions, cell pre-treatment with resveratrol (0.1-10 μM) restored basal DDAH activity and ADMA level with a dose-dependent effect. Piceatannol acted as resveratrol on DDAH pathway but at 10-fold lower concentrations. Resveratrol and piceatannol restored DDAH activity even in the presence of splitomicin, a specific inhibitor of Sirtuin 1. These results suggest potential therapeutic intervention targeting resveratrol or piceatannol administration to improve endothelial dysfunction.     

肠道菌群在应激诱发大鼠高血压中的作用

观察应激性高血压大鼠肠道菌群的变化,探索肠道菌群在应激性高血压发生中的作用。应激性高血压模型的制备:大鼠每天2次接受足底电刺激加噪声的应激,每次2 h,中间间隔4 h,共14 d。血压的测量:大鼠股动脉插管,Powerlab系统记录血压。伪无菌鼠的制备:在大鼠的饮用水中加入氨苄西林(1 g/L)、万古霉素(500 mg/L)、新霉素(1 g/L)和甲硝唑(1 g/L)4种抗生素,共持续4周。采用Illumina MiSeq测序技术,测定大鼠粪便中微生物16S rRNA V3-V4区序列,并对群落结构和多样性进行比较分析。慢性应激导致大鼠血压升高,心率加快,血清去甲肾上腺素浓度增加;α多样性分析显示应激大鼠肠道菌群丰富度和多样性下降,β多样性分析显示应激组大鼠肠道菌群物种组成变少,差异性变大;伪无菌鼠的肠道菌群物种单一,仅有少量的变形菌门。给予伪无菌鼠相同的慢性应激,不能引起大鼠血压升高、心率增快,血清去甲肾上腺素浓度未升高。应激引起大鼠肠道菌群紊乱,应激性高血压的发生可能依赖于肠道菌群的状态。