冷刺激条件下硒和维生素E对大鼠心脏内血管活性物质的影响

目的：用低硒／维生素E(Se／VE)饲料喂养的大鼠动物模型,施以冰冰在刺激,观察Se,VE对心肌血管活性物质的影响。方法：用60只Wistar大鼠,按体重和性别随机分为低硒／维生素EI组（Se/VEDGI）及上述每kg饲料补硒（亚硒酸钠）0.1mg（Se／VEDGI＋Se）组、补a－VE100mg（Se／VEDGI＋VE）组、联合补Se,VE（Se／VEDGI＋Se／VE）组、低硒／维生素EII组（Se／VEDGII）和常规饲料组（SG)等六组。饲养70d,测定各组动物心肌内皮素（ET）,一氧化氮（NO）,去甲管上腺素（NE）,血管紧张素II（Ang－II）,单胶氧化酶（MAO－A）,超氧化物歧化酶（SOD）,谷胱甘肽过氧化物酶（GSH－Px）,脂褐素（lipofuscin）等水平。结果：Se／VEDG组心肌ET,Ang－II含量明显高于其它组;NO含量明显低于其它组;心肌NE水平增高,而特异性分解NE的MAO－A活性降低;心肌Lipofusein含量明显增加;SOD,GSH－Px含量降低。补Se组、补SE／VE组、低Se/VEII组和对照组上述指标活性明显改善。结论：冷刺激条件下硒和维生素E对大鼠心脏内血管活性物质有明显影响。     

紫外线照射充氧自血回输对梭曼急性中毒肝脏自由基损伤保护作用的实验研究

目的:探讨家兔梭曼中毒后肝脏自由基损伤情况及研究紫外线照射充氧自血回输(ultraviolet blood irradiation andoxygenation,UBIO)的保护作用。方法:健康家兔100只随机分为5组,每组20只,雌雄不拘,包括正常对照组、中毒组、常规治疗组、UBIO治疗组及UBIO联合常规治疗(复合治疗)组,连续观察14天,记录家兔存活率,检测肝组织中总抗氧化力(T-AOC)、超氧化物歧化酶SOD、过氧化氢酶CAT、谷胱甘肽过氧化物酶(GSH-Px),谷胱甘肽转硫酶GST活性及丙二醛MDA含量。结果:家兔梭曼中毒后肝脏T-AOC、SOD、GSH-Px、GST活性明显低于正常对照组(P<0.01),而CAT活性及MDA含量明显高于正常对照组(P<0.01)。在经UBIO治疗或复合治疗后,肝组织中T-AOC、SOD、GSH-Px、CAT、GST活性明显高于(P<0.05),而MDA含量明显低于中毒组(P<0.01)。结论:家兔梭曼中毒后可引起肝脏自由基损伤,UBIO治疗有明显的保护作用,因而可以用于急性梭曼中毒的治疗或辅助治疗。     

维生素E在体内外具有抗氧化作用

目的探讨维生素E在体内外的应激损伤。方法体外实验:人肝RBL细胞系根据H_2O_2损伤及损伤前后给予维生素E分为4组,对照组(C)、H_2O_2损伤组(Ec)、H_2O_2损伤前(Eb)及后(Ea)给维生素E组;体内实验:将20只清洁级雄性Wistar大鼠分为对照组和大及小剂量维生素E组,每天进行一次35和15 mg/kg溶液2 m L灌胃,连续3 d。体外实验应用MTT和TUNEL法检测细胞存活率和凋亡率,免疫印迹和免疫组化方法检测细胞中NF-κB、Hsp-70、Bcl-2、Bax及caspase-3的表达水平;体内实验应用生化法检测3和6 d后血浆内T-AOC、SOD、GSH和MDA的水平。结果 H_2O_2损伤组(Ec)细胞凋亡率增加(P0.01),细胞内Bax、Hsp-70、NF-κB及caspase-3显著升高(P0.01),而Bcl-2显著下降(P0.01),维生素E干预后能显著缓解上述变化(P0.01),H_2O_2损伤前干预效果优于后干预。灌胃后3 d血浆中T-AOC、SOD、GSH的水平增高,MDA降低(P0.01),6 d后其相关指标变化更加显著(P0.05)。结论维生素E可通过调节人肝RBL细胞相关蛋白表达水平和Wistar大鼠血浆中抗氧化酶体系而发挥抗氧化作用。     

大鼠侧脑室内注射β淀粉样蛋白(25～35)致氧化应激反应的动态变化

观察外源性β淀粉样蛋白（β－Amyloid peptide,Aβ)25-35引起大鼠大脑的氧化应激。于大鼠侧脑室内一次性注射聚集态的Aβ（25－35）15nmol后，5，9和14d分别测定海马的脂质过氧化产物丙二醛（malodialdehyde,MDA)含量的还原型谷胱甘肽（reduced glutathione,GSH)水平以及谷胱革肽过氧化物酶（glutathione peroxidase,GSH-PX)和超氧化物歧化酶（Superoxide dismutase,SOD)活性。与对照组相比，Aβ组大鼠术后5d时MDA含量增加（P＜0．05），抗氧化酶GSH－PX活性下降（P＜0．001），9d时GSH－PX和SOD活性显著升高（P＜0．01和P＜0．05）。14d时，两组间各个指标均无明显差别。结果表明在大鼠脑室内一次性注射Aβ（25－35）可导致氧化应激反应，这一改变与时间相关，可被机体抗氧化系统所代偿。     

高交感活性诱导的大鼠心肌损伤模型中氧化应激的受体调控机制*

 目的：研究高交感活性诱发大鼠心肌损伤的氧化应激受体调控机制。方法：Sprague-Dawley (SD)大鼠随机分为对照组、模型组、普萘洛尔（Pro) 组、哌唑嗪(Praz)组、普萘洛尔+哌唑嗪 (Pro+Praz) 组、维生素E(VE)组及普萘洛尔+哌唑嗪+维生素E (Pro+Praz+VE) 组,除对照组外其余各组均腹腔注射去甲肾上腺素(NE) 复制高交感活性引起的心肌损伤模型,同时灌胃给予相应药物,连续给药16 d,期间监测各组动物体重的变化。16 d后进行心室重构指标（心指数和羟脯氨酸含量）、病理组织学检查、氧化/抗氧化指标（MDA、SOD、CAT、GSH-Px和T-AOC）和能量代谢指标（Na+-K+ATPase和Ca2+-Mg2+ATPase）分析。结果：从第9天开始,模型组动物体重与对照组的比较差异有统计学意义（P<0.05）,心指数和左心室肥厚明显增加,氧化/抗氧化和能量代谢障碍;Pro、Praz、Pro+Praz和VE各组均出现不同程度的动物体重、心指数、左心室肥厚和氧化/抗氧化失衡的改善;Pro、Praz和Pro+Praz能明显升高左心室Na+-K+ATPase和Ca2+-Mg2+ATPase的活性,Pro+Praz作用最明显（P<0.05）。结论：肾上腺素受体依赖是高交感活性诱导心肌氧化应激损伤的重要途径。     

谷胱甘肽治疗中度妊高征对机体抗氧化系统及新生儿窒息影响的研究

目的探讨低分子抗氧化剂谷胱甘肽在中度妊高征治疗中的作用。方法检测实验组与对照组中度妊高征各 30例脐血中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)、维生素E、维生素C、5项指标,并观察新生儿窒息发生率,进行统计分析。结果治疗组血中MDA水平下降(P<0．01),而GSH、VE、VC(P<0．01)上升,SOD无变化(P>0．05)。结论低分子抗氧化剂谷胱甘肽与维生素E、维生素C联合应用可减少中度妊高征时的自由基损伤,降低了新生儿窒息的发生率。     

糖尿病大鼠心肌病理变化及脂质过氧化和一氧化氮的改变

目的：研究糖尿病心肌的病理变化及其发生机制。方法：用光镜及透射电镜观察四氧嘧啶诱导的糖尿病1个月大鼠心肌形学改变,并测定心肌细胞超氧化物歧化酶（SOD）、谷膛甘肽过氧化物酶（GSH－Px)、一氧化氮合酶（NOS）的活性及一氧化氮（NO）、丙二醛（MDA）含量。结果：光镜下见心肌细胞萎缩、嗜酸性变及空泡变性,间质纤维增生,透射电镜下见线粒体扩张、嵴变短,内质网扩张,骨原纤维破坏,间质胶原纤维增生。SOD、GSH－Px活性下降,NOS活性及NO、MDA含量增加。结论：糖尿病大鼠心肌病变主要为心肌萎缩、线粒体扩张及肌原纤维破坏,间质纤维增生,脂质过氧化作用及NO所致的损伤可参与其中。     

腺病毒潜伏感染对大鼠肺泡上皮细胞氧化/抗氧化平衡的影响

目的：研究腺病毒潜伏感染对大鼠肺泡上皮细胞氧化/抗氧化平衡的影响。方法: 构建稳定表达腺病毒E1A蛋白的大鼠肺泡上皮细胞，检测氧化剂刺激时GSH、MDA的含量变化和主要抗氧化酶SOD、CAT、GPx、GST以及γ-GCS酶活性的变化。 结果：腺病毒E1A蛋白通过抑制大鼠肺泡上皮细胞内γ-GCS酶的活性，抑制了氧化应激时GSH的合成和GPx及GST酶的活性；腺病毒E1A蛋白下调了细胞在氧化应激后的恢复能力。结论： 腺病毒潜伏感染扩大了大鼠肺泡上皮细胞氧化应激时的氧化/抗氧化失衡，而腺病毒E1A蛋白抑制γ-GCS酶的活性是其中的关键环节。     

一氧化氮合酶抑制剂对大鼠结肠炎损伤的影响

目的：了解一氧化氮合酶抑制剂L－精氨酸甲酯（L-NAME）对大鼠结肠炎损伤的影响。方法：将实验大鼠随机分为对照组、损伤组、NAME1、NAME2、NAME3（即N1、N2、N3）干预组。采用三硝基苯磺酸（TNB）30 mg+50%乙醇0.25 mL给大鼠灌肠复制结肠炎模型，并检测各组的溃疡指数（UI）、一氧化氮（NO）、MDA含量及GSH活性。结果：N1、N2、N3组的NO、UI、MDA值低于损伤组，GHS值高于损伤组，对照组的损伤不明显。相关分析表明，NO含量与MDA含量呈正相关，与GSH活性呈负相关。结论：在结肠炎症反应中，NO过量生成具有损伤作用，L－NAME通过抑制NOS活性，减少NO及自由基的生成，具一定的抗损伤作用。     

慢性乙型肝炎高胆红素血症患者氧化损伤的研究

目的探讨慢性乙型肝炎（CHB）高胆红素血症患者氧化损伤的情况。方法75例血清总胆红素（TBIL）高于正常上限值（ULN）的CHB患者,按TBIL为ULN的倍数分为A、B、C、D、E五组。测定患者血清丙二醛（MDA）、黄嘌呤氧化酶（XOD）、维生素C（VC）、维生素E（VE）浓度,并做出统计分析。11例健康志愿者为正常对照组,16例乙肝表面抗原（HBsAg）携带者为携带者组。结果各患者组与正常对照组比较：MDA、XOD浓度升高,差异有统计学意义（P〈0．05）,VCVE浓度降低,差异有统计学意义（P〈0．05）;携带者组与正常对照组比较：XOD浓度升高,差异有统计学意义（P〈0．05）,MDA、VC、VE浓度差异无统计学意义（P〉0．05）。在CHB高胆红素血症患者中,MDA、XOD浓度与TBIL水平呈正相关（r=0．670,P〈0．01;r=0．737,P〈0．01）;VC、VE浓度与TBIL水平呈负相关（r=-0．463,P〈0．01;r=-0．247,P〈0．05）。各患者组间的比较：除A、B组间外,其余各组间MDA浓度差异有统计学意义（P〈0．05）;A、B、C组与D、E组间XOD浓度差异有统计学意义（P〈0．05）;A组与D、E组,B、C、D组与E组间VC浓度差异有统计学意义（P〈0．05）;A、B组与E组间VE浓度差异有统计学意义（P〈0．05）。结论CHB高胆红素血症患者体内存在氧化-抗氧化功能障碍,血清TBIL水平升高时氧化损伤程度加重。HBsAg携带者体内氧化损伤程度不高。抗氧化损伤可能有助于CHB高胆红素血症患者的治疗。     

褪黑激素对老年大鼠肝MDA含量和GSH—px、CAT，Ca^2＋—ATPase活性的影响

为探讨褪黑激素保肝抗衰老的作用及其机理 ,文章观察了褪黑激素对老年大鼠肝过氧化脂质产物含量和氧自由基、细胞内钙离子清除能力的影响。连续 30天给初老大鼠补充褪黑激素后 ,用生化比色法测定了肝组织内丙二醛 (MDA)含量和谷胱甘肽过氧化物酶 (GSH- px) )、氢过氧化物酶(CAT)、钙离子 -三磷酸腺苷酶 (Ca2 - ATPase)活性。与对照组比较 ,实验组大鼠肝内 MDA含量下降了 31.2 % ,GSH- px、CAT和 Ca2 - ATPase活性分别提高了 2 5.1%、49.6%和 2 5.4%。提示 ,褪黑激素能增强肝细胞抗氧化能力和清除细胞内游离钙离子的能力 ,具有一定的保护肝细胞和抗衰老作用。     

褪黑激素对老年大鼠肾MDA含量和GSH—px、CAT、Ca^2＋—ATPase活性的影响

为探讨褪黑激素在抗肾老化的作用及机理，观察了褪黑激素对老年大鼠肾过氧化脂质产物的含量及对氧自由基与细胞内钙离子清除能力的影响。本实验连续３０ 天给初老大鼠补充褪黑激素，采用生化比色法测定了肾组织内丙二醛（ＭＤＡ）含量和谷胱甘肽过氧化物酶（ＧＳＨｐｘ）、氢过氧化物酶（ＣＡＴ）与钙离子三磷酸腺苷酶（Ｃａ２＋ ＡＴＰａｓｅ）活性。与对照组比较，实验组大鼠肾组织ＭＤＡ 含量下降了１２７％ ，而ＧＳＨｐｘ、ＣＡＴ 和Ｃａ２＋ ＡＴＰａｓｅ 活性则分别提高了２７５％ 、２９５％ 和３９８％ 。提示　褪黑激素能增强肾抗氧化能力和清除游离钙离子的能力，对延缓肾结构老化和肾功能减退具有一定的作用     

Protective Effect of Glutathione Against Liver Warm Ischemia‐Reperfusion Injury in Rats is Associated with Regulation of P‐Selectin and Neutrophil Infiltration

We examined the effects of glutathione (GSH) preconditioning through the portal vein on rat warm liver ischemia reperfusion injury (I/R injury) and investigated the mechanisms involved. In rats with warm liver I/R injury, administration of GSH by means of the portal vein before ischemia increased the 7‐day survival rates of rats after liver I/R from 38% to 75%. This effect was correlated with significantly improved liver function, depressed MDA content in the liver and fewer histologic features of hepatocyte injury. Intrahepatic expression of P‐selectin and infiltration of neutrophils were increased significantly after liver I/R. GSH pretreatment decreased intrahepatic MPO content and the expression of P‐selectin. However, it did not significantly affect the mRNA levels for P‐selectin after liver I/R. Thus, preconditioning with GSH protects the liver against I/R injury by a mechanism dependent on free radical species scavenging, down‐regulation of adhesion molecule expression and inhibition of neutrophil accumulation. These findings document the potential clinical utility of GSH to improve the overall success of diverse procedures, such as liver surgery and liver transplantation. Anat Rec, 291:1016–1022, 2008. © 2008 Wiley‐Liss, Inc.     

Influence of subchronic administration of catechol estrogens on the formation of reactive oxygen species in rat liver microsomes.

Metabolic pathways of estrogens are the formation of catechol estrogens (CE; 2- and 4-hydroxy-estrogens), redox cycling of CE and free radical generation, mediated through cytochrome P450 (P450) oxidase/reductase activity. In previous investigations subchronic administration of estrogens showed prooxidative and antioxidative activities in rat liver microsomes (BARTH et al. 1999). To find out whether or not catechol metabolites are responsible for prooxidative activity, we checked 2- and 4-hydroxy-estradiol (2OH-E2 and 4OH-E2) and the non-catechol metabolite 6alpha-hydroxy-estradiol (6alpha-OH-E2) for formation of reactive oxygen species in liver microsomes of 30-day-old male Wistar rats after 5 days treatment (1, 10 mg/kg b. wt. orally, once a day). The results were compared with those after treatment of the rats with estradiol (E2), estradiol valerate (E2V) and ethinylestradiol (EE2). In liver homogenates glutathione and lipid peroxides were determined, in microsomes NADPH-Fe++-stimulated lipid peroxidation (LPO), H2O2 generation and lucigenin (LUC) and luminol (LUM) amplified chemiluminescence (CL) were investigated. In liver 9000 x g supernatants monooxygenase activities were measured. The two catechol estrogens did not show any antioxidative activity, whereas 6alpha-OH-E2 significantly diminished lipid peroxides in the liver as well as LPO and LUM-CL in liver microsomes. Among estrogens, only EE2 showed antioxidative activity. Both CE inhibited ethoxycoumarin O-deethylation. Peroxidative activity as enhanced LUC-CL was found after 2OH-E2 (1 mg/kg b.wt.) and E2, but 10 times higher doses of both CE did not change LUC-CL. Microsomal H2O2 generation was enhanced by E2, E2V and both CE, not by 6alpha-OH-E2. The lower level of H2O2 enhancement caused by CE in comparison to E2 and E2V together with unchanged LUC-CL after high CE doses did not unequivocally prove the CE to be mainly responsible for the prooxidative activities of E2 and E2V in liver microsomes, at least in 30-day-old male rats. Unchanged GSH in the liver after CE administration supports this hypothesis.     

金丝桃苷对CCl4诱导大鼠急性肝损伤抗氧化应激研究

目的研究金丝桃苷（Hyp）对四氯化碳（CCI。）诱导大鼠急性肝损伤的治疗作用。方法采用大鼠CCl4急性肝损伤模型,观察Hyp对急性肝损伤大鼠肝脏组织病理学改变的影响;检测肝组织匀浆中超氧化物歧化酶（T-SOD）、谷胱甘肽（GSH）的活性及丙二醛（MDA）含量变化。结果CCl4模型组大鼠肝组织HE染色病理检测结果见明显炎症变性死及纤维组织增生现象;Hyp高剂量60mg／kg、中剂量30mg／kg治疗组的肝组织病理改变明显改善;Hyp治疗组肝组织中T—SOD、GSH活性明显升高,MDA含量明显降低,并存在量效关系。结论Hyp对CCl4引起的大鼠急性肝损伤有较好的治疗作用,其机制可能与其抗氧化活性有关。     

Puerarin protects the rat liver against oxidative stress-mediated DNA damage and apoptosis induced by lead

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. In this study, we valuated the protective effect of puerarin against lead-induced oxidative DNA damage and apoptosis in rat liver. A total of forty male Wistar rats (8-week-old) was divided into 4 groups: control group; lead-treated group (500 mg Pb/l as the only drinking fluid); lead + puerarin treated group (500 mg Pb/l as the only drinking fluid plus 400 mg PU/kg bwt intra-gastrically once daily); and puerarin-treated group (400 mg PU/kg bwt intra-gastrically once daily). The experimental period was lasted for 75 successive days. Our data showed that puerarin significantly effectively improved the lead-induced histology changes in rat liver and decreased the serum ALT and AST activities in lead-treated rats. Puerarin markedly restored Cu/Zn-SOD, CAT and GPx activities and the GSH/GSSG ratio in the liver of lead-treated rat. Furthermore, the increase of 8-hydroxydeoxyguanosine induced by lead was effectively suppressed by puerarin. The enhanced caspase-3 activity in the rat liver induced by lead was also inhibited by puerarin. TUNEL assay showed that lead-induced apoptosis in rat liver was significantly inhibited by puerarin, which might be attributed to its antioxidant property. In conclusion, these results suggested that puerarin could protect the rat liver against lead-induced injury by reducing ROS production, renewing the activities of antioxidant enzymes and decreasing DNA oxidative damage.     

Effect of Methylsulfonylmethane on Paraquat-Induced Acute Lung and Liver Injury in Mice

Methylsulfonylmethane (MSM) is a natural organosulfur compound that exhibits antioxidative and anti-inflammatory effects. This study was carried out to investigate the effect of MSM on paraquat (PQ)-induced acute lung and liver injury in mice. A single dose of PQ (50 mg/kg, i.p.) induced acute lung and liver toxicity. Mice were treated with MSM (500 mg/kg/day, i.p.) for 5 days. At the end of the experiment, animals were euthanized, and lung and liver tissues were collected for histological and biochemical analysis. Tissue samples were used to determine malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and tumor necrosis factor-α (TNF-α) levels. Blood samples were used to measure plasma alanine transaminase (ALT), γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Histological examination indicated that MSM decreased lung and liver damage caused by PQ. Biochemical results showed that MSM treatment significantly reduced tissue levels of MDA, MPO, and TNF-α, while increased the levels of SOD, CAT, and GSH compared with PQ group. MSM treatment also significantly reduced plasma levels of ALT, GGT, and ALP. These findings suggest that MSM as a natural product attenuates PQ-induced pulmonary and hepatic oxidative injury.     

牛磺酸和甘糖酯对糖尿病大鼠自由基防御机能和肾脏功能的影响

目的：探讨牛磺酸和甘糖酯对糖尿病（ＤＭ）大鼠体内自由基防御机能和肾功能的影响。方法：牛磺酸（３００ｍｇ／ｋｇ ＢＷ）甘糖酯（１００ｍｇ／ｋｇ ＢＷ）给予ＤＭ大鼠３周后,检查体内抗氧化酶活性,抗氧化物质水平和肾脏功能。     

肠缺血再灌注时肠粘膜抗氧化系统及肝、肾功能改变的实验研究

目的：研究肠缺血再灌注损伤时肠粘膜抗氧化系统的改变及对肝、肾功能的影响。 方法： 复制大鼠肠缺血再灌注模型，采用分光光度计生化测定方法检测肠粘膜的还原型谷胱甘肽GSH、谷胱甘肽-S-转移酶GST、过氧化氢酶CAT、丙二醛MDA、超氧化物岐化酶SOD、谷胱甘肽过氧化物酶GSH-Px及血清谷丙转氨酶ALT、谷草转氨酶AST、尿素氮BUN、肌酐Cr的改变。 结果： 肠粘膜MDA含量于再灌注2 h显著高于假手术组(P<0.05)，再灌注4 h较假手术组高116%(P<0.05)，24 h较前有所降低但仍高于假手术组(P<0.05)；GSH含量于再灌注2 h显著低于假手术组(P<0.05)，再灌注4 h低至假手术组的40%（P<0.01），12 h恢复；肠粘膜CAT、SOD和GSH-Px活性未见明显改变；GST活性于再灌注2 h较假手术组低39%，再灌注4 h达最低，较假手术组低43%(P<0.05)，12 h恢复至假手术组水平；血清ALT、AST、 BUN及Cr于再灌注2 h显著高于假手术组(P<0.05)，再灌注4 h分别较假手术组高208%、100%、103%、41%（P<0.01），24 h基本恢复。 结论： 肠缺血45 min再灌注使肠粘膜GSH含量和GST活性降低，MDA含量增加，并造成肝肾功能的可逆性损伤。