β-胡萝卜素对阿霉素致大鼠心肌组织的超氧化物歧化酶、谷胱甘肽过氧化物酶mRNA表达改变的影响

目的研究β-胡萝卜素(BC)对阿霉素(ADM)所致大鼠心肌组织的锰超氧化物歧化酶(Mn SOD)mRNA、铜-锌超氧化物歧化酶(Cu-Zn SOD)mRNA、谷胱甘肽过氧化物酶(GPx)mRNA表达改变的影响,探讨BC拮抗ADM导致心肌组织的Mn SOD、Cu-Zn SOD、GPx活性降低的机制。方法大鼠腹腔注射(ip)ADM(10·0mg·kg-1,1次);ADM处理的大鼠灌胃(ig)不同剂量的BC(每天1次,3次;ipADM前igBC,每天1次,11次行预处理)进行干预。分别用硫代巴比妥酸法、硝酸还原酶法、黄嘌呤氧化酶法、二硫代二硝基苯甲酸法、血红蛋白氧化法测定心肌组织的丙二醛(MDA)含量、一氧化氮(NO)含量、Mn SOD及Cu-Zn SOD活性、GPx活性、一氧化氮合酶活性;RT-PCR方法检测心肌组织的Mn SODmRNA、Cu-Zn SOD mRNA、GPx mRNA、诱导型一氧化氮合酶(iNOS)mRNA表达。结果BC(20·0,40·0,80·0mg·kg-1)拮抗ADM所致心肌组织的MDA含量及NO含量增加、iNOS mRNA表达水平增加及其酶活性增加(P<0·01);拮抗ADM所致心肌组织的Mn SOD mRNA、Cu-Zn SOD mR-NA、GPx mRNA表达水平降低及其酶活性降低(P<0·01)。结论BC拮抗ADM导致心肌组织的Mn SOD mRNA、Cu-ZnSOD mRNA、GPx mRNA表达降低而拮抗ADM导致Mn SOD、Cu-Zn SOD、GPx活性降低。其机制可能与BC抑制ADM诱导心肌组织的iNOS mRNA表达而降低iNOS活性使心肌组织产生NO减少,从而减少NO抑制Mn SOD mRNA、Cu-ZnSOD mRNA、GPx mRNA表达有关。     

S-甲基异硫脲对阿霉素致大鼠心肌脂质过氧化的影响

目的　研究S 甲基异硫脲 (SMT)对阿霉素 (ADM )所致大鼠心肌脂质过氧化的影响。方法　 32只Wistar大鼠随机分成 4组 :对照组 ;SMT组 (SMT 5 0mg·kg-1,iv ,1次 ) ;ADM组 (ADM 5 0mg·kg-1,ip ,1次 ) ;ADM +SMT组(ADM、SMT的剂量及用法分别同ADM组、SMT组 )。于给药后 2 4h处死所有大鼠。分别用TBA法、硝酸还原酶法、DTNB法、邻苯三酚自氧化法、血红蛋白氧化法测定心肌的脂质过氧化物 (LPO)含量、一氧化氮 (NO)含量、谷胱甘肽过氧化物酶 (GPx)活性、超氧化物歧化酶 (SOD)活性、一氧化氮合酶活性 ;用免疫组织化学法检测心肌的硝基酪氨酸(NT)水平。结果　SMT干预ADM处理的大鼠后 ,降低心肌的LPO及NO含量、诱导型一氧化氮合酶 (iNOS)活性、NT水平 (P <0 0 1) ,增加心肌的SOD及GPx活性 (P <0 0 1)。SMT、ADM对心肌的结构型一氧化氮合酶活性无影响 (P >0 0 5 )。结论　SMT抑制ADM导致心肌脂质过氧化。其机制可能与SMT选择性地抑制ADM所诱导心肌的iNOS活性使心肌产生NO减少而减少心肌生成过氧亚硝基阴离子、保护心肌的SOD及GPx活性有关。     

硫普罗宁对阿霉素心脏毒性的保护作用及机制

目的：研究硫普罗宁（MPG）对阿霉素（ADM）心脏毒性的保护作用及机制。方法：建立ADM损伤大鼠心脏模型,灌胃给予MPG,检测血清肌钙蛋白Ⅰ（cTnⅠ）、肌酸激酶同工酶（CK-MB）及脑钠肽（BNP）、心肌组织超氧化物歧化酶（SOD）活力,丙二醛（MDA）、一氧化氮（NO）含量及一氧化氮合酶（NOS）的活性,并观察心肌组织病理改变。结果：与ADM大鼠心脏模型组相比,MPG干预ADM处理后大鼠的血清cTnⅠ、CK—MB及BNP显著降低（P〈0．05或P〈0．01）,心肌组织SOD活力显著增高,MDA、NO含量,总NOS活力及iNOS活力显著降低（P均〈0．01）,心肌组织病理积分显著下降（P〈0．05）。结论：MPG对ADM心脏毒性具有较好的保护作用;MPG可能通过恢复心肌组织SOD的活力、抑制iNOS活性使心肌组织NO产生减少,从而减轻ADM所致大鼠心肌组织的氧化损伤。     

硫普罗宁对阿霉素心脏毒性的保护作用及机制

目的：研究硫普罗宁（MPG）对阿霉素（ADM）心脏毒性的保护作用及机制。方法：建立ADM损伤大鼠心脏模型,灌胃给予MPG,检测血清肌钙蛋白工（cTnⅠ）、肌酸激酶同工酶（CK—MB）及脑钠肽（BNP）、心肌组织超氧化物歧化酶（SOD）活力,丙二醛（MDA）、一氧化氮（NO）含量及一氧化氮合酶（NOS）的活性,并观察心肌组织病理改变。结果：与ADM大鼠心脏模型组相比,MPG干预ADM处理后大鼠的血清cTnI、CK．MB及BNP显著降低（P〈0．05或P〈0．01）,心肌组织SOD活力显著增高,MDA、NO含量,总NOS活力及iNOS活力显著降低（P均〈0．01）,心肌组织病理积分显著下降（P〈0．05）。结论：MPG对ADM心脏毒性具有较好的保护作用;MPG可能通过恢复心肌组织SOD的活力、抑制iNOS活性使心肌组织NO产生减少,从而减轻ADM所致大鼠心肌组织的氧化损伤。     

1,6-二磷酸果糖对阿霉素导致大鼠心肌细胞凋亡的影响

目的　研究 1,6 二磷酸果糖 (FDP)对阿霉素 (ADM )导致大鼠心肌细胞凋亡的影响。方法　给大鼠腹腔注射ADM ( 2 5 0mg·kg-1,隔日 1次 ,共 6次 )处理大鼠 ;给ADM处理的大鼠腹腔注射不同剂量的FDP(隔日 1次 ,共 2 1次 )进行干预。分别用TBA法、硝酸还原酶法、DTNB法、邻苯三酚自氧化法测定心肌的脂质过氧化物 (LPO)含量、一氧化氮 (NO)含量、谷胱甘肽过氧化物酶 (GPx)活性、超氧化物歧化酶 (SOD)活性 ;用透射电镜技术和TUNEL法检测心肌细胞凋亡 ;用原位杂交法检测心肌的诱导型一氧化氮合酶 (iN OS)mRNA表达。结果　FDP( 3 0 0 ,60 0 ,12 0 0mg·kg-1)干预ADM处理的大鼠后 ,均可降低心肌的LPO及NO含量、减少心肌细胞的凋亡数量、降低心肌iNOSmRNA的表达水平、增加心肌的SOD及GPx活性。结论　FDP抑制ADM导致心肌细胞凋亡 ,减轻ADM对心肌的毒性损伤 ,其机制2 0 0 1 0 4 12收稿 ,2 0 0 1 0 5 30修回 广西自然科学基金 (No 982 40 0 1)和广西教育厅科学基金 (No 1999 34 9)资助1 广西肿瘤研究所生化室 ,南宁　 5 30 0 2 1作者简介 :阳冠明 ,男 ,39岁 ,医学硕士 ,副研究员 ,硕士生导师。Tel:0 771 5 35 8130 (O) ,5 35 130 5 (H) ;林善修 ,男 ,67岁 ,教授 ,博士生导师可能与其保护心肌的SOD及GPx活性、抗脂质?     

左旋精氨酸和超氧化物歧化酶联合对大鼠心肌缺血再灌注损伤的影响

目的观察左旋精氨酸（L-Arg）及超氧化物歧化酶（SOD）在大鼠心肌缺血再灌注损伤中的作用。方法40只大鼠完全随机分为L—Arg组、SOD组、L—ArgSOD组及对照组各10只。在心肌缺血再灌注期间分别给予含L—Arg、SOD、L-Arg＋SOD及不含L—Arg和SOD的KH灌注液,期间测定心脏功能指标、乳酸脱氢酶、肌酸磷酸激酶、一氧化氮、心肌组织丙二醛含量。结果心肌缺血再灌注期间,各组间心率差异无统计学意义。L—Arg组左心室内压力高于对照组[分别为（71．2±3．7）mmHg和（52．3±4．3）mmHg],冠状动脉流量也高于对照组[分别为（87．4±13．5）m]／min和（64．2±11．2）ml／min]（P〈0．05）;SOD组左心室内压力[分别为（74．3±3．4）mmHg]也高于对照组（P〈0．05）,L—Arg＋SOD组左心室内压力[（78．6±3．2）mmHg]和冠状动脉流量高于L-Arg组和SOD组,差异有统计学意义（P〈0．05）。在缺血再灌注10min时,L—Arg组和SOD组乳酸脱氢酶、肌酸激酶均较对照组减少（P〈0．05）,L—Arg＋SOD组乳酸脱氢酶、肌酸激酶均较L—Arg组和SOD组减少（P〈0．01）;L．Arg组冠状动脉流出液NO含量高于对照组（P〈0．05）;SOD组冠状动脉流出液NO含量和对照组相比差异无统计学意义;L-Arg＋SOD组略高于L-Arg组,但差异无统计学意义。与对照组相比,SOD组、L．Arg＋SOD组心肌丙二醛含量均明显降低（P〈0．01）,但这2组间差异无统计学意义。L—Arg组心肌丙二醛含量和对照组相比,差异无统计学意义。结论L—Arg和SOD在心肌缺血再灌注损伤中有保护作用,二者联合效果更明显。     

复方丹参滴丸对心肌保护作用的实验研究

为探讨复方丹参滴丸（DSP）对心肌损伤的保护作用机制，将120只大鼠随机分为4组：异丙肾上腺素（ISO）损伤组、DSP保护组、DSP＋ISO组及正常对照组。应用ISO腹腔内注射造成心肌缺血损伤，测定大鼠血清及心肌组织中脂质过氧化物丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性及血浆中内皮素（ET）和血清中一氧化氮（NO）含量的变化。结果表明，DSP保护组血浆中NO含量升高，与正常对照组差异有显性；DSP保护组注射ISO后MDA、SOD、ET及NO变化程度明显小于单纯ISO组，差异有显性。结论：复方丹参滴丸具有良好的抗急性心肌缺血损伤作用，其作用机制与抗自由基及血管内皮保护效应密切相关。     

1,6-二磷酸果糖对阿霉素导致大鼠心肌酪氨酸硝基化的影响

目的　研究 1,6 二磷酸果糖 (FDP)对阿霉素 (ADM )导致大鼠心肌酪氨酸硝基化的影响。方法　给大鼠腹腔注射ADM(2 5 0mg·kg-1,隔日 1次 ,共 6次 )处理大鼠 ;给ADM处理的大鼠腹腔注射不同剂量的FDP(隔日 1次 ,共2 1次 )进行干预。分别用TBA法、硝酸还原酶法、邻苯三酚自氧化法测定心肌的脂质过氧化物 (LPO)含量、一氧化氮(NO)含量、超氧化物歧化酶 (SOD)活性 ;分别用原位杂交法、免疫组织化学法检测心肌的诱导型一氧化氮合酶 (iN OS)mRNA表达、硝基酪氨酸 (NT) ,半定量分析心肌的iNOSmRNA表达水平、NT水平。结果　FDP(30 0 ,6 0 0 ,12 0 0mg·kg-1)干预ADM处理的大鼠后 ,均可显著降低心肌的LPO及NO含量、显著降低心肌的iNOSmRNA表达水平、显著降低心肌的NT水平、显著增加心肌的SOD活性 (P <0 0 1)。结论　FDP抑制ADM导致心肌酪氨酸硝基化而减轻ADM对心肌的毒性损伤。其机制可能与FDP抑制ADM引起心肌的iNOSmRNA表达而使心肌产生NO减少 ,以及FDP保护心肌的SOD活性而增强心肌清除超氧阴离子的能力 ,从而减少心肌生成过氧亚硝基阴离子有关     

西红花酸对阿霉素所致大鼠心肌线粒体损伤的影响

目的：研究西红花酸对阿霉素所致大鼠心肌线粒体损伤的保护作用。方法：建立阿霉素致大鼠心脏毒性模型，观察西红花酸对心肌线粒体膜电位、线粒体DNA断裂程度、细胞色素C氧化酶活性及其亚基ⅡmRNA表达的影响；测定心肌线粒体超氧阴离子含量及谷胱甘肽过氧化物酶（GSH-PX）活性。结果：与模型组相比，西红花酸可明显升高线粒体膜电位，降低线粒体DNA断裂程度，提高细胞色素C氧化酶活性及其亚基ⅡmRNA表达水平，显著降低心肌线粒体超氧阴离子含量，提高GSH—PX活性。结论：西红花酸能明显减轻阿霉素所致大鼠心肌线粒体损伤。     

罗格列酮改善糖尿病大鼠早期肾脏病变机制的研究

目的：探讨罗格列酮对糖尿病大鼠早期肾脏病变的改善作用及其机制。方法：采用链脲菌素（STZ）诱导的糖尿病大鼠模型作为研究对象。每日给予罗格列酮5mg·kg^-1、20mg·kg^-1灌胃,共4周。检测各组大鼠的血糖（BS）、血脂及24h尿白蛋白水平。随后处死大鼠,测定肾组织中丙二醛（MDA）含量、总抗氧化能力（T—AOC）及铜锌超氧化物歧化酶（Cu—ZnSOD）、谷胱甘肽过氧化酶（GSH—Px）、转录激活蛋白-1（AP—1）的活性。同时留取肾脏组织作PAS染色进行病理检查。分别用逆转录-聚合酶链式反应（PT—PCR）和免疫组化法检测肾组织中转化生长因子-β1（TGF—β1）mRNA及蛋白质的含量。结果：与糖尿病组相比,罗格列酮20mg·kg^-1干预组Bs、血脂水平无明显变化,但肾脏MDA、TGF—β1 mRNA及蛋白质含量明显下降,AP-1活性虽有所降低,但没有显著性差异。而肾脏抗氧化酶活性,包括SOD、GSH—Px、T—AOC则明显上升。病理检查发现该组较糖尿病组肾小球面积、体积减小。结论：罗格列酮可明显改善糖尿病大鼠的早期肾脏损害。机制可能与其抗氧化,下调TGF—β1的表达有关。     

Toxicity of ad lib. overfeeding: effects on cardiac tissue.

The aim of the present study was to determine the effects of ad lib. overfeeding and of dietary restriction (DR) on oxidative stress in cardiac tissue. Lipoperoxide concentrations were decreased and antioxidant enzymes were increased in moderate-DR-fed rats. Severe-DR induced increased lipoperoxide concentrations. Overfeeding increased lipoperoxide levels in cardiac tissue. Total superoxide dismutase (SOD) and Cu-Zn superoxide dismutase (Cu-Zn SOD) activities were decreased in cardiac tissue at 35 days of overfeeding. As no changes in glutathione peroxidase (GSH-Px) were observed in overfed rats, while SOD and Cu-Zn SOD activities were decreased in these animals, it is assumed that superoxide anion is an important intermediate in the toxicity of ad lib. overfeeding. Overfeeding induced alterations in markers of oxidative stress in cardiac tissue.     

Effects of antenatal dexamethasone on antioxidant enzymes and nitric oxide synthase in the rat lung

We investigated the effects of prenatal dexamethasone (DEX) administration on antioxidant enzymes (AOEs) and nitric oxide synthase (NOS) in fetal and neonatal rat lungs. DEX (1 mg/kg, s.c., for 2 days) or vehicle alone was administered to pregnant rats, and the lungs of fetuses on days 19 and 21 of gestation and of 1- and 3-day-old neonates were examined. We measured protein levels of the AOEs manganese superoxide dismutase and copper-zinc superoxide dismutase (Mn SOD and Cu-Zn SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and inducible and endothelial nitric oxide synthase (i-NOS and e-NOS). Mn SOD, GSH-Px, and e-NOS expression gradually increased with increasing gestational and postnatal age in the lungs of the control groups. Cu-Zn SOD, CAT, and i-NOS expression did not change with increasing gestational and postnatal age in the lungs of the control groups. DEX administration had significant effects on i-NOS and e-NOS protein and mRNA expression. The increased Mn SOD, GSH-Px, and e-NOS expressions during the perinatal period suggests that antenatal developmental changes in AOEs in the lungs of premature fetuses could be reduced by reactive oxygen species-mediated injury at birth. Furthermore, antenatal glucocorticoid treatment may accelerate the development of lungs via the two types of NOS.     

Effects of selenium deficiency on the response of cardiac tissue to ischemia and reperfusion

Over a 10-week period, female Wistar rats received a diet containing a low level of selenium, cofactor of the antioxidant enzyme glutathione peroxidase (GPx) in order to examine the influence of deficiency of this trace element (i) on tissue antioxidant enzyme defence systems, and (ii) on the susceptibility of the myocardium to ischemia-reperfusion injury. At the end of the dietary treatment, hearts were perfused at constant flow (11 ml/min) before being subjected to 15 min of global normothermic ischemia, followed by 30 min of reperfusion. The effects of selenium deficiency were estimated by studying functional recovery of various cardiac parameters (left ventricular developed pressure LVDevP, heart rate HR, and the product HR x LVDevP), as well as ultrastructural tissue characteristics. Furthermore, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured at the end of the reperfusion period. Results suggest that: (a) the activity of GPx is decreased by selenium deficiency while SOD activity remains unchanged, (b) the recovery of cardiac function and myocardial ventricular ultrastructure during reperfusion are altered in the selenium-deficient group compared to controls. These results illustrate the crucial role that selenium, the co-factor of one of the major antioxidant enzymes of the myocardium, plays in determining the vulnerability of the heart to ischemia and reperfusion.     

Protective effects of L-arginine on pulmonary oxidative stress and antioxidant defenses during exhaustive exercise in rats

AIM: To assess the effects of L-arginine (L-Arg) supplementation on pulmonary oxidative stress and antioxidant defenses in rats after exhaustive exercise. METHODS: Rats were randomly divided into four groups: sedentary control (SC), sedentary control with L-Arg treatment (SC+Arg), exhaustive exercise with control diet (E) and exhaustive exercise with L-Arg treatment (E+Arg). Rats in groups SC+Arg and E+Arg received a 2% L-Arg diet. Rats in groups E and E+Arg underwent an exhaustive running test on a motorized treadmill. Pulmonary oxidative stress indices [xanthine oxidase (XO), myeloperoxidase (MPO), and malondialdehyde (MDA)] and antioxidant defense systems [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH)] were investigated in this study. RESULTS: L-Arg supplementation significantly reduced exercise-induced elevations of XO and MPO activities in lung. L-Arg reversed the exercise-induced increase in SOD and GR activities, but increased CAT and GPX activities. L-Arg administration also significantly increased the GSH levels in plasma. CONCLUSION: L-Arg supplementation can prevent elevations of XO and MPO activities in the lung and favorably influence pulmonary antioxidant defense systems after exhaustive exercise.     

Exacerbative role of vitamın A on radiation damage in vivo

Purpose In our study, after applying a single dose of 612 cGy irradiation, we aimed to observe the role of free radicals on tissue damage in liver caused by irradiation, by measuring the nitric oxide (NO) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities, and the amount of thiobarbituric acid reactive substance (TBARS), which is an indicator of free-radical damage. On the other hand we investigated whether tissue damage can be prevented by vitamin A or not. Materials and methods The study was performed on three groups: (1) the control group, (2) the group to which irradiation was administrated, and (3) the group which was given irradiation + vitamin A. The irradiation group of animals was given a single dose of gamma irradiation at a sublethal dose. In the group to which both irradiation and vitamin A were administered, vitamin A was given for 2 days prior to irradiation. The amount of NO was measured by electron spin resonance (ESR) spectroscopy, whereas SOD, GPx and TBARS were measured by spectrophotometry. Results and conclusion As a result of irradiation-mediated tissue damage in liver, we observed a NO loss and an increase in TBARS amount. Administration of vitamin A before irradiation resulted in an increase in both NO and TBARS and a decrease in SOD and GPx enzyme activities. Together, these data indicate that vitamin A may play an exacerbative role in free-radical-mediated tissue damage.