CIC对高脂膳食大鼠肝脏氧化应激的影响

目的:研究慢性间断性冷暴露(mild chronic intermittent cold exposure,CIC)对高脂膳食大鼠肝脏氧化应激的影响。方法:轻度CIC已被广泛用于建立冷适应研究的动物模型。本研究通过将大鼠暴露于温和的CIC和/或高脂膳食4w,检测肛温、体重、肝脏重量、ATP和活性氧(ROS)的水平,Western blot检测冷诱导RNA结合蛋白(cold inducible RNA binding protein,Cirbp)和硫氧还蛋白(Thioredoxin,TRX)的蛋白表达。结果:同对照组相比,高脂膳食组体重显著增加,血清和肝脏ROS水平显著升高,ATP水平没有显著影响。同对照组相比,CIC暴露1w后大鼠肛温显著降低,而2w、3w和4w周肛温没有显著差异,ROS水平无显著差异,但ATP水平显著升高;Cirbp和TRX的表达显著升高。同常温高脂膳食组相比,CIC暴露4w后,大鼠体重显著降低,ROS水平无显著差异,而ATP水平显著升高;Cirbp和TRX的表达水平显著升高。这些结果均提示冷适应增强了高脂膳食大鼠肝脏的抗氧化水平,可能是由于冷适应后Cirbp表达升高,继而调控其下游的抗氧化蛋白TRX的表达增加,从而清除ROS的缘故。结论:CIC暴露诱导的冷适应可保护肝脏免于高脂膳食诱导的氧化应激。     

高脂膳食对大鼠血液内糖脂代谢相关激素水平的影响

目的：探讨高脂膳食对大鼠血液内瘦素（leptin）、胰岛素（insulin）、胰高血糖素（glucagon）、单核细胞趋化蛋白-1（MCP-1）、胰多肽（PP）和酪酪肽（PYY）水平的影响。方法：将SD大鼠随机分为高脂饲料组（H组）和普通饲料组（C组）。8周后将H组中大鼠根据体重情况再分为肥胖易感组（OS组）和肥胖抵抗组（OR组）。使用ELISA方法检测激素水平。结果：OS组大鼠血leptin、insulin和MCP-1水平均显著高于C组;OS组和OR组大鼠血glucagon水平均显著高于C组;OR组大鼠血PYY水平显著低于C组。结论：高脂膳食可导致OS组和OR组大鼠血glucagon水平升高,并可导致OS组大鼠血leptin、insulin和MCP-1水平升高,以及OR组大鼠血PYY水平的下降。     

高糖高脂膳食诱导大鼠肝脏ChREBPmRNA表达

目的：观察高糖高脂膳食对大鼠肝组织碳水化合物反应元件结合蛋白（ChREBP）表达的影响。方法：16只雄性SD大鼠随机分为2组,对照组给予普通饲料,高糖高脂组给予高糖高脂饲料。6周后,检测血脂和肝组织中ChREBP表达水平。结果：高糖高脂膳食组ChREBPmRNA表达水平、血总甘油三酯、总胆固醇和高密度脂蛋白浓度均显著高于对照组（P〈0．05）;血低密度脂蛋白明显低于对照组（P〈0．05）。结论：高搪高脂膳食能引起肝脏组织中碳水化合物反应元件结合蛋白表达增加。     

高脂膳食对小鼠生化及病理形态的影响

目的高脂膳食对机体血液、组织匀浆中各种生化指标的影响,尤其是对胆固醇等脂质代谢的影响,为研究高胆固醇引起的心血管等疾病建立模型。方法将C57BL/6 j小鼠63只随机分为2组。普食组（用普通饲料饲喂）12只,雌雄各6只,高脂组（用高脂饲料饲喂）51只,雌26只、雄25只。单笼饲喂,饲喂期为67 d。观察动物体重、摄食量、比较血液以及肝、肾组织匀浆中有关脂类代谢和抗氧化方面的生化指标以及组织病理学观察。结果高脂组血液中胆固醇（TC）和低密度脂蛋白胆固醇（LDLC）均显著高于普食组（P〈0.05）;高脂组肝、肾脏组织匀浆中T-AOC、CuZn-SOD、SOD、AKP、NOS、MDA的水平与普食组相比均无统计学差异;与普食组相比,雄性小鼠摄食量差异显著（P〈0.05）、体重差异不显著;病理观察可见高脂组中肝细胞空泡变性。结论通过高脂膳食成功的建立了高胆固醇血症模型,该模型有可能在胆固醇浓度升高引起的脂质代谢异常、动脉粥样硬化、冠心病和其他代谢性疾病的研究中发挥作用。     

有氧运动联合黑果枸杞对高脂膳食大鼠心肌脂代谢某些指标的影响

目的:研究有氧运动联合黑果枸杞对高脂膳食大鼠心肌脂代谢某些指标的影响。方法:55只雄性Wistar大鼠经过适应性饲养4 d后进行20 min/d的无负重游泳训练,连续3 d,筛选淘汰5只不适应游泳训练的大鼠后,按体重以数字随机分组法分为5组:普通膳食+安静组(RDC组)、高脂膳食+安静组(HDC组)、高脂膳食+黑果枸杞+安静组(HDLC组)、高脂膳食+有氧运动组(HDM组)、高脂膳食+黑果枸杞+有氧运动组(HDLM),每组10只。HDM组和HDLM组进行6周每周6次60 min/d的无负重游泳训练。RDC组大鼠以普通饲料常规喂养;其余各组以高脂饲料喂养; HDLC组和HDLM组大鼠灌胃黑果枸杞,灌胃剂量为4.48 g/(kg·d),灌胃体积为5 ml/kg,其余各组灌胃等量蒸馏水。6周后,测定大鼠Lee’s指数,取血、心肌检测相关生化指标。结果:与RDC组比较,HDC组Lee’s指数,血清FFA、TNF-α、IL-6、TC、TG、LDL-C,心肌FFA、ICAM-1显著升高(P<0.01);血清HDL-C水平显著降低(P<0.01)。与HDC组比较,HDLC、HDM、HDL...     

有氧运动联合破壁蛋白核小球藻对高脂膳食大鼠脂代谢某些指标的影响

目的：研究有氧运动联合破壁蛋白核小球藻对高脂膳食大鼠脂代谢某些指标的影响。方法：55只雄性Wistar大鼠经过适应性饲养4 d后进行3 d、20 min/d的无负重游泳训练,筛选淘汰5只不适应游泳训练的大鼠后,按体重以数字随机分组法分为5组：普通膳食+安静对照组（C组）、高脂膳食+安静对照组（H组）、高脂膳食+小球藻+安静对照组（HC组）、高脂膳食+有氧运动组（HM组）、高脂膳食+有氧运动+小球藻组（HMC）,每组10只。HM组和HMC组进行6周每周6次60 min/d的无负重游泳训练。C组大鼠以普通饲料常规喂养;其余各组以高脂饲料喂养;HC组和HMC组大鼠灌胃破壁小球藻1次,灌胃剂量为3.9 g/（kg·d）,灌胃体积为5 ml/kg,其余各组ig等量生理盐水。6周后,测定大鼠Lee’s指数,取血、肝脏检测相关生化指标。结果：与C组比较,H组Lee’s指数,血清FFA、IL-6、TNF-α、TC、TG、LDL-c,肝脏FFA、IL-10显著升高（P<0.01）;血清HDL-c水平显著降低（P< 0.01）。与H组比较,HC、HM、HMC组Lee’s指数,血清FFA、IL-6、TNF-α、TC、TG、LDL-c,肝脏FFA、IL-10显著降低（P<0.05或P<0.01）;血清HDL-c水平显著升高（P<0.05或P<0.01）。与HC、HM组比较,HMC组Lee’s指数,血清FFA、IL-6、TNF-α、TC、TG、LDL-c,肝脏FFA、IL-10显著降低（P<0.05）;血清HDL-c水平显著升高（P<0.05）。结论：有氧运动和破壁蛋白核小球藻干预能够不同程度改善高脂膳食大鼠脂代谢,降低肥胖对肝脏造成的脂毒性。其中联合干预较单一干预更为有效。     

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。     

胶原蛋白肽对高脂日粮小鼠抗氧化能力和血脂代谢的影响

本文探讨胶原蛋白肽对高脂日粮小鼠抗氧化能力及血脂代谢的影响。40只小鼠随机分为5组(n=8):分别饲喂正常日粮,高脂日粮,添加0.5%和1%胶原蛋白肽及0.1%硫辛酸的高脂日粮。42 d后测定小鼠全血(血清)和组织活性氧(Reactive oxygen species,ROS)水平、丙二醛(Malondialdehyde,MDA)含量、抗氧化酶活力及血脂水平。结果表明:0.5%和1%胶原蛋白肽都可显著降低机体ROS水平及MDA含量(P<0.05),增强抗氧化能力(P<0.05),改善血脂水平(P<0.05)。1%胶原蛋白肽能使机体抗氧化能力及血脂水平恢复到正常水平,0.5%的添加量效果不显著。适量的胶原蛋白肽可有效提高机体抗氧化能力,缓解高脂膳食造成的氧化应激,改善血脂代谢。     

山楂总黄酮对心肌缺血大鼠尿液代谢谱的影响北大核心CSCD

为了研究山楂总黄酮对异丙肾上腺素(ISO)诱导的心肌缺血大鼠尿液代谢谱的影响及其代谢通路,取雄性SD大鼠24只,随机分为正常组、模型组和山楂总黄酮组(0. 276 g/kg),灌胃给药,连续5天。~1H NMR检测大鼠尿液代谢物变化,并进行模式识别分析。确认了6个生物标志物,山楂总黄酮(0. 276 g/kg)上调TMAO、Creatinine(P <0. 05),下调DMA、DMG、Hippurate、Citrate(P <0. 05)。通路分析表明山楂总黄酮可能通过调节钙超载、氧化应激、三羧酸循环以及肾功能改善心肌缺血。本文为在细胞和分子水平阐释山楂总黄酮抗心肌缺血的作用机制提供了参考,为筛选山楂总黄酮中的抗心肌缺血成分提供了代谢组学分析手段。     

高脂膳食对肥胖易感和肥胖抵抗大鼠学习记忆能力的影响及机制

经过长期的高脂膳食后并非所有个体都会发生肥胖,还有些个体会产生肥胖抵抗现象。高脂膳食影响海马依赖的学习记忆等认知功能已被广泛证实,但目前关于高脂膳食对肥胖抵抗个体学习记忆能力影响的研究仍较少见。本文旨在对比研究高脂膳食对肥胖易感（obesity-prone, OP）和肥胖抵抗（obesity-resistant, OR）大鼠空间学习记忆能力的影响,并探讨其潜在的可能机制。Morris水迷宫结果显示,肥胖易感大鼠的学习能力显著低于对照大鼠和肥胖抵抗大鼠,但3组大鼠的记忆功能无显著性差异。Western印迹结果显示,与对照组相比,肥胖易感和肥胖抵抗大鼠海马内脑源性神经营养因子(BDNF)、血管内皮细胞生长因子(VEGF)和突触素(SYN)的含量均显著降低,丙二醛(MDA)和白介素1β(IL-1β)的含量均显著升高;且肥胖易感大鼠海马内上述蛋白质含量的变化更明显。免疫荧光染色和激光共聚焦显微镜扫描结果均显示,肥胖易感大鼠的海马神经发生水平显著低于肥胖抵抗大鼠和对照大鼠,但肥胖抵抗大鼠的海马神经发生水平与对照大鼠相比未见显著性变化。这些结果提示,高脂膳食可能是通过降低海马内突触可塑相关蛋白质的表达和神经发生,以及加剧炎症反应来损害肥胖易感大鼠的空间学习能力,而对肥胖抵抗大鼠的学习记忆能力影响不显著。     

Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet

Oxidative stress, physical inactivity and high-fat (FAT) diets are associated with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects of physical training (PT) were evaluated in rats with MS induced by FAT diet for 13 weeks, on oxidative stress and insulin signaling in the liver, during the last 6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine aminotransferase, glucose and insulin. Livers of FAT-SED rats increased superoxide dismutase activity, thiobarbituric acid-reactive substances, protein carbonyl and oxidized glutathione (GSSG); and decreased catalase activity, reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin, total cholesterol, MAP and HR; and their livers increased superoxide dismutase and catalase activities, the reduced glutathione/GSSG ratio and the expression of peroxisome proliferator-activated receptor gamma and insulin receptor compared to FAT-SED rats. These findings indicated adaptive responses to PT by restoring the oxidative balance and insulin signaling in the liver and certain biometric and biochemical parameters as well as MAP in MS rats.     

Black tea polyphenols modulate xenobiotic-metabolizing enzymes,oxidative stress and adduct formation in a rat hepatocarcinogenesis model

The present study was designed to investigate the modulatory effects of black tea polyphenols (Polyphenon-B) on phase I and phase II xenobiotic-metabolizing enzymes and oxidative stress in a rat model of hepatocellular carcinoma (HCC). Liver tumours induced in male Sprague-Dawley rats by dietary administration of ρ-dimethylaminoazobenzene (DAB) increased cytochrome P450 (total and CYP1A1, 1A2 and 2B isoforms), cytochrome b₅, cytochrome b₅ reductase, glutathione S-transferase (GST total and GST-P isoform) and gamma-glutamyltranspeptidase (GGT) with decrease in quinone reductase (QR). This was accompanied by enhanced lipid and protein oxidation and compromised antioxidant defences associated with increased expression of the oxidative stress markers 4-hydroxynonenal (4-HNE), anti-hexanoyl lysine (HEL), dibromotyrosine (DiBrY) and 8-hydroxy 2-deoxyguanosine (8-OHdG). Dietary administration of Polyphenon-B effectively suppressed DAB-induced hepatocarcinogenesis, as evidenced by reduced preneoplastic and neoplastic lesions, modulation of xenobiotic-metabolizing enzymes and amelioration of oxidative stress. Thus, it can be concluded that Polyphenon-B acts as an effective chemopreventive agent by modulating xenobiotic-metabolizing enzymes and mitigating oxidative stress in an in vivo model of hepatocarcinogenesis.     

Effect of dietary tea polyphenols on growth performance and cell-mediated immune response of post-weaning piglets under oxidative stress

To gain insights into the effects of tea polyphenols (TP) on growth performance and cell-mediated immune response of piglets under oxidative stress, an oxidative stress model was established by intraperitoneally injecting weaned piglets with diquat. After intake of either basal diet or TP-supplemented diet for 7 d, half of the piglets in each group were challenged with diquat. Results showed that dietary TP alleviated growth depression to some extent. A T lymphocyte transformation test (LTT) demonstrated that TP promoted the proliferation and activation of T lymphocytes. The ratio of CD4+/CD8+ was elevated, indicating a recovering tendency from immune damages caused by oxidative stress. The increment of pro-inflammatory IL-1 caused by oxidative stress was attenuated, and the concentration of serum IFN-γ was decreased by TP-supplementation. However, the serum concentrations of anti-inflammatory cytokine, such as IL-4, were greatly enhanced by TP, which suggested an immune shift from Th1 to Th2. These findings supported the immunomodulatory potential of TP for piglets subjected to oxidative stress.     

Protective effects of green tea polyphenol against reactive oxygen species-induced oxidative stress in cultured rat calvarial osteoblast

The injurious effects of reactive oxygen species on osteoblasts and the potential protective role played by green tea polyphenols (GtPP) were investigated using primarily cultured rat calvarial osteoblasts. Oxidative stress was induced in cultured osteoblasts, either by adding 100 mmol/L H2O2 or by the action of 40 U/L xanthine oxidase (XO) in the presence of xanthine (250 micromol/L). After incubation, the cellular viability, function and morphology were evaluated. Both treatments produced a significant reduction in osteoblast viability, as assessed by a two-colored fluorescence staining method combined with flow cytometric analysis and MTT assay. A significant reduction in the alkaline phosphatase activity was observed after H2O2 addition, whereas XO did not have the same effect. On the microscopic observations, the morphological changes and intracellular ultrastructural damages were remarkably induced by both treatments. The H2O2-induced alterations were prevented by pre-incubating the osteoblasts with 200 microg/ml GtPP for 1 h. When the oxidative stress was induced by XO, the cellular viability and morphology was also maintained at the same polyphenol concentration. These results demonstrate that GtPP can act as a biological antioxidant in a cell culture experimental model and protect cells from oxidative stress-induced toxicity.     

An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila

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槲皮素体外抗氧化及对小鼠血脂代谢作用的研究

本研究旨在探讨槲皮素体外抗氧化能力以及对高脂日粮小鼠血脂代谢的影响.体外分别测定了槲皮素对DPPH·,·OH和ABTS+·自由基的清除作用.动物实验:将昆明种雄性小鼠32只,随机分为4组,分别饲喂正常、高脂、高脂+0.05g/kg槲皮素、高脂+0.1g/kg槲皮素日粮.9周后测定小鼠肝脏活性氧(Reactive oxygen species,ROS)水平、丙二醛(Malondialdehyde,MDA)含量、抗氧化酶活力及血脂水平.结果表明:槲皮素对DPPH·,·OH和ABTS+·具有较强的清除作用,在一定范围内呈现出明显的剂量增加-效应增强的关系.0.05g/kg槲皮素能显著降低肝脏自由基水平及MDA含量(P＜0.05),增强抗氧化能力(P＜0.05),改善血脂水平(P＜0.05),而0.1g/kg槲皮素效果不显著.结论:0.05g/kg槲皮素可有效提高机体抗氧化能力,缓解高脂膳食造成的氧化应激,改善血脂代谢.     

Long-term high-fat diet induces pancreatic injuries via pancreatic microcirculatory disturbances and oxidative stress in rats with hyperlipidemia

Stromal cell-derived factor 1 (CXCL12) is an angiogenic chemokine that is believed to act solely via its cognate receptor CXCR4. Evidence is now provided for the existence of a different CXCL12 binding and signaling receptor on endothelial cells. Bovine aortic endothelial cells (BAECs) strongly expressed CXCR4 and exhibited high binding capacity for fluorescently labeled CXCL12. However, CXCL12 binding was not correlated with the CXCR4 expression level and was virtually unaffected by the specific CXCR4 antagonists AMD3100 or T22. Similar observations were made in endothelial cells of mouse and human origin. Also, AMD3100 failed to block CXCL12 internalization and CXCL12-induced intracellular signal transduction via extracellular signal-regulated kinases 1/2 in BAECs. In contrast, CXCL12 binding and signaling were almost completely inhibited by the CXCR4 antagonist in T-lymphoid SupT1 cells. Together, our data point to the existence of an additional receptor through which CXCL12 exerts its biological effects in endothelial cells.     

The effect ofGongronema latifolium extracts on serum lipid profile and oxidative stress in hepatocytes of diabetic rats

Diabetes is known to involve oxidative stress and changes in lipid metabolism. Many secondary plant metabolites have been shown to possess antioxidant activities, improving the effects of oxidative stress on diabetes. This study evaluated the effects of extracts from Gongronema latifolium leaves on antioxidant enzymes and lipid profile in a rat model of non insulin dependent diabetes mellitus (NIDDM). The results confirmed that the untreated diabetic rats were subjected to oxidative stress as indicated by significantly abnormal activities of their scavenging enzymes (low superoxide dismutase and glutathione peroxide activities), compared to treated diabetic rats, and in the extent of lipid peroxidation (high malondialdehyde levels) present in the hepatocytes. The ethanolic extract of G. latifolium leaves possessed antioxidant activity as shown by increased superoxide dismutase and glutathione peroxidase activities and decreases in malondialdehyde levels. High levels of triglycerides and total cholesterol, which are typical of the diabetic condition, were also found in our rat models of diabetes. The ethanolic extract also significantly decreased triglyceride levels and normalized total cholesterol concentration.     

Alpha-lipoic acid affects the oxidative stress in various brain structures in mice with methionine and choline deficiency

Deficiency in methionine or choline can induce oxidative stress in various organs such as liver, kidney, heart, and brain. This study was to examine the effects of alpha-lipoic acid (LA) on oxidative stress induced by methionine and choline deficiency (MCD) in several brain structures. Male mice C57BL/6 (n = 28) were divided into four groups: (1) control – continuously fed with standard chow; (2) LA – fed with standard chow and receiving LA; (3) MCD2 – fed with MCD diet for two weeks, and (4) MCD2+LA – fed with MCD diet for two weeks and receiving LA (100 mg/kg/day intraperitonealy [i.p.]). Brain tissue (cortex, hypothalamus, striatum and hippocampus) was taken for determination of oxidative stress parameters. MCD diet induced a significant increase in malondialdehyde and NOx concentration in all brain regions, while LA restored their content to normal values. Similar to this, in MCD2 group, activity of total SOD, MnSOD, and Cu/ZnSOD was reduced by MCD diet, while LA treatment improved their activities in all brain structures. Besides, in MCD2 group a decrease in catalase activity in cortex and GSH content in hypothalamus was evident, while LA treatment induced an increase in catalase activity in cortex and striatum and GSH content in hypothalamus. LA treatment can significantly reduce lipid peroxidation and nitrosative stress, caused by MCD diet, in all brain regions by restoring antioxidant enzymes activities, predominantly total SOD, MnSOD, and Cu/ZnSOD, and to a lesser extent by modulating catalase activity and GSH content. LA supplementation may be used in order to prevent brain oxidative injury induced by methionine and choline deficiency.     

茶多酚对营养性肥胖大鼠肝脏自由基代谢的影响

目的:探讨茶多酚对营养性肥胖大鼠肝脏自由基代谢的影响。方法:采用高脂饲料喂养,体重(200±20)g的雄性SD大鼠32只,随机分为4组(n=8),测定各组大鼠肝脏细胞O自由基和N自由基。结果:高脂饲料组大鼠肝脏超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性显著提高,茶多酚补充组丙二醛(MDA)含量比对照组及高脂饲料组显著下降;高脂饲料组大鼠肝脏TNOS、iNOS活性及NO含量显著升高,茶多酚降低了总-氧化氮合酶(TNOS)、诱导型一氧化氮合酶(iNOS)活性及NO含量。结论:高脂饲料诱导了大鼠肝脏细胞的氧化应激状态,茶多酚提高了营养性肥胖大鼠肝脏的抗氧化能力,对营养性肥胖大鼠肝脏有一定的保护作用。