吸烟所致宫内发育迟缓孕鼠肝脏药物代谢酶及抗氧化酶活性的变化

目的:研究和探讨吸烟所致宫内发育迟缓(IUGR)大鼠母体肝脏药物代谢酶活性和抗氧化功能的改变及其所带来的毒理学和药理学意义。方法:妊娠天数明确的Wistar大鼠16只,分为对照组和吸烟组。采用吸烟法建立大鼠IUGR模型,孕21d剖腹取胎,测量胎鼠生长发育指标(体重、身长、尾长)和胎盘重。差速离心法制备孕鼠肝亚细胞组分,测定多种药物代谢酶和抗氧化酶活性。结果:IUGR大鼠胎仔平均体重、身长、尾长、胎盘重都明显低于对照组,分别为对照组的87.7%、94.5%、95.3%和83.0%(P<0.01)。母体肝脏微粒体细胞色素P450(CYP)1A1活性升高,为对照组的137.9%(P<0.05);而CYP3A活性降低,为对照组的73.3%(P<0.05),谷胱甘肽S转移酶(GST)活性也降低,为对照组的86.5%(P<0.05)。母体肝脏胞浆超氧化物歧化酶(SOD)和过氧化氢酶(Cat)活性降低(P<0.05);谷胱甘肽过氧化物酶(GSHPx)活性升高,为对照组的1.11倍(P<0.05)。结论:孕期吸烟可致IUGR大鼠母体肝脏部分药物代谢酶活性和抗氧化系统功能改变,这些改变可能是导致IUGR发生的原因之一,同时吸烟可能改变孕期用药的疗效,增加药物毒性。     

Time-course of changes in hepatic lipid peroxidation and glutathione metabolism in rats with carbon tetrachloride-induced cirrhosis

1. The aims of the present study were to assess: (i) the temporal relationships between hepatic lipid peroxidation, changes in the glutathione detoxification system and the onset/development of cirrhosis in CCl4-treated rats; and (ii) the effects of oral zinc administration on these parameters. 2. Cirrhosis was induced in 120 rats by intraperitoneal injections of CCl4 twice a week over 9 weeks. One hundred and twenty additional animals were used as controls. Both groups were further subdivided to receive either a standard diet or one supplemented with zinc. Subsets of 10 animals each were killed at weeks 1, 2, 3, 5, 7 and 9 from the start of the study. 3. Induction of cirrhosis produced a decrease in the components of the hepatic glutathione anti-oxidant system: glutathione transferase activity decreased from week 1, the concentration of reduced glutathione (GSH) decreased from week 5 and glutathione peroxidase (GPx) activity decreased from week 7. This impairment was chronologically related to an increase in free radical generation. Hepatic lipid peroxidation was significantly correlated with GPx activity (r = -0.47; P < 0.001) in CCl4-treated rats. Zinc administration did not produce any significant improvement of the hepatic glutathione system. 4. In conclusion, cirrhosis induction in rats by CCl4 administration produced a decrease in the hepatic glutathione antioxidant system that was related to an increase in free radical production. Furthermore, zinc supplementation produced a reduction in the degree of hepatic injury and a normalization of lipid peroxidation, but not an improvement of the hepatic GSH anti-oxidant system.     

胸腺和性激素对大鼠肝脏脂质过氧化的调节作用(英文)

本文应用成年去胸腺或去性腺Wistar大鼠研究了胸腺对肝脏脂质过氧化(LPO)的影响及其与性激素有关的中间途径,结果表明,雌性成年去胸腺(ATx)大鼠肝匀浆丙二醛(MDA)含量增高,但雄性ATx大鼠肝脏MDA无明显变化;同时雌性ATx大鼠血浆雌二醇水平下降,雄性ATx大鼠血浆睾酮浓度降低,雌性大鼠卵巢切除术后肝脏MDA的变化与胸腺切除术后的变化相似,给予雌二醇可逆转去卵巢大鼠肝脏MDA的增高,在雄性大鼠中,无论是切除睾丸还是睾丸切除后补充睾酮对肝脏MDA均无明显影响,此外,给雌性ATx大鼠注射雌二醇可逆转其肝脏MDA的增高,这些结果提示胸腺在调节雌性大鼠肝脏抗氧化功能中起着重要作用,这种作用可能通过雌激素介导,因此我们设想在体内可能存在:胸腺-雌激素-肝脏通路”,它参与对肝脏抗氧化功能的调节。     

N-乙酰半胱氨酸对实验性肝硬化大鼠肝纤维化与脂质过氧化的影响

目的:探讨N-乙酰半胱氨酸(NAC)对肝硬化大鼠的作用及其影响肝纤维化与脂质过氧化损伤的机制。方法:雄性Wistar大鼠36只,随机分成正常组(7只)、模型组(14只)、NAC组(15只)。以10μL·kg~(-1)剂量二甲基亚硝胺(DMN)腹腔注射,每周连续3d,每日1次,共4 wk,诱导大鼠肝硬化模型。成模后,NAC组以NAC 0．1 g·kg~(-1)灌胃,每日1次,共4 wk;模型组给予等量生理盐水灌胃。HE染色与天狼猩红染色观察肝组织炎症与胶原沉积;水解法测定肝组织羟脯氨酸含量;生化法检查血清肝功能指标[丙氨酸转氧酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)、清蛋白(Alh)等],肝组织超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量;Western印迹法检测肝组织α-平滑肌肌动蛋白(α- SMA)与热休克蛋白47(HSP47)表达。结果:治疗4 wk后,模型组大鼠死亡7只,NAC组死亡3只, NAC明显提高肝纤维化大鼠的生存率(P＜0．01)。与正常组相比,模型大鼠肝脏肝细胞变性、坏死明显,炎性细胞浸润,胶原沉积并形成假小叶;血清ALT、AST和TBil升高,AIb下降;肝组织羟脯氨酸与MDA含量升高,SOD活性下降(P＜0．01)。而NAC可显著减轻肝脏炎症、肝细胞坏死与肝组织胶原沉积,改善模型大鼠异常的肝功能指标,降低肝组织羟脯氧酸与MDA含量,提高SOD活性(P＜0．05,P＜0．01),抑制模型大鼠肝组织HSP47与α-SMA蛋白的表达(P＜0．01)。结论:N-乙酰半胱氨酸有良好的治疗肝硬化作用,其作用机制与促进肝纤维化逆转及抗肝脏脂质过氧化有关。     

异莲心碱对大鼠肝匀浆脂质过氧化的影响

目的:研究异莲心碱(isoliensinine,IL)对大鼠肝匀浆脂质过氧化的影响.方法:用硫代巴比妥酸(TBA)法测定异莲心碱对大鼠肝匀浆自氧化及Vit C-Fe2 系统诱导引起的脂质过氧化产物丙二醛的含量.结果:异莲心碱能显著抑制大鼠肝匀浆自氧化及Vit C-Fe2 系统诱导所产生MDA的含量,且呈现出一定的量效关系,达到50%抑制率所需药物浓度IC50分别为0.67 g·L-1和1.05 g·L-1.结论:异莲心碱具有显著的抗脂质过氧化作用.     

琉璃苣油对脂质代谢和脂质过氧化的影响

在高脂饲料中加入６％的琉璃苣油饲喂Ｗｉｓｔａｒ♂大鼠３ｗｋ，其大鼠血清甘油三酯（ＴＧ）、总胆固醇（ＴＣ）、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）、ＴＣ／ＨＤＬ－Ｃ、ＬＤＬ－Ｃ／ＨＤＬ－Ｃ增加值和高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）、高密度脂蛋白亚组分Ⅱ胆固醇（ＨＤＬ２－Ｃ）、ＨＤＬ２－Ｃ与高密度脂蛋白亚组分Ⅲ胆固醇ＨＤＬ３－Ｃ比值及卵磷脂胆固醇酰基转移酶（ＬＣＡＴ）活性的下降显著低于单纯食猪油的高脂对照组，琉璃苣油组大鼠血清ＬＤＬ－Ｃ水平低于月见草油组。高脂摄入所致大鼠肝脂质和肝过氧化脂质（ＬＰＯ）水平增高，谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活性下降，琉璃苣油致肝脂质过氧化作用低于月见草油。     

Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice

Context: The application of bleomycin is limited due to its side effects including lung toxicity. Silymarin is a flavonoid complex isolated from milk thistle [Silybum marianum L. (Asteraceae)] which has been identified as an antioxidant and anti-inflammatory compound.

Objective: This study evaluates the effect of silymarin on oxidative and inflammatory parameters in the lungs of mice exposed to bleomycin.

Materials and methods: BALB/c mice were divided into four groups of control, bleomycin (1.5?U/kg), bleomycin plus silymarin (50 and 100?mg/kg). After bleomycin administration, mice received 10?d intraperitoneal silymarin treatment. On 10th day, blood and lung samples were collected for measurement of oxidative and inflammatory factors.

Results: Silymarin led to a decrease in lung lipid peroxidation (0.19 and 0.17?nmol/mg protein) in bleomycin-injected animals. Glutathione-S-transferase (GST) which was inhibited by bleomycin (32.4?nmol/min/mg protein) induced by higher dose of silymarin (41?nmol/min/mg protein). Silymarin caused an elevation in glutathione (GSH): 2.6 and 3.1?µmol/g lung compare with bleomycin-injected animals 1.8?µmol/g lung. Catalase (CAT) was increased due to high dose of silymarin (65.7?µmol/min/ml protein) compare with bleomycin treated-mice. Myeloperoxidase (MPO) which was induced due to bleomycin (p?p?Conclusions: Silymarin attenuated bleomycin induced-pulmonary toxicity. This protective effect may be due to the ability of silymarin in keeping oxidant–antioxidant balance and regulating of inflammatory mediator release.     

脂质过氧化在再灌流性肝损伤中的作用

采用低流率-再灌流模型研究脂质过氧化在再灌流性肝损伤中的作用,肝脏经过90min低速率灌流未见明显损伤,当灌流速率恢复到正常后中心静脉周围区(PC区)细胞发生迅速不可逆损害,并伴有丙二醛生成率大幅度上升,低速率灌流期间,灌流液中黄嘌呤与次黄嘌吟浓度由原来的1.5和3.6μmol·L~(-1)逐步升高至5.5和11.5μmol·L~(-1),自由基清除剂儿茶酸能使再灌流期丙二醛生成率由295 nm01·g~(-1)·h~(-1)下降至109 nmol·g~(-1)·h~(-1),并使LDH释放率减少约50％,PC区细胞死亡率减少89％,再灌流初期用氮饱和灌流液冲洗3 min,使再灌流所致的LDH释放下降约50％,PC区细胞死亡率减少84％,别嘌吟醇(2～6mmol·L~(-1))对防止再灌流性肝损伤表现出明显的剂量效应关系。 与预计结果相反低浓度别嘌呤醇(0.5～1mmol·~(-1))能增加再灌流性肝损伤,400μmol·L~(-1)黄嘌呤则使再灌流性肝损伤明显减轻,其代谢产物尿酸对降低再灌流时丙二醛生成率以及细胞损害均表现出明显的剂量反应关系。     

七叶皂苷素对肢体缺血-再灌注脂质过氧化反应影响的临床观察

目的观察七叶皂苷素对肢体缺血-再灌注脂质过氧化反应的临床效果。方法选择40例肢体手术需充气带加压肢体止血的患者,随机分为对照组（n=20）和治疗组（n=20）。治疗组患者术前10min静脉滴入七叶皂苷素注射液16mg,对照组患者给等量平衡液。肢体缺血前,再灌注后30、90、180min分别检测血丙二醛（MDA）、肌酸磷酸激酶（CPK）和超氧化物歧化酶（SOD）。结果肢体缺血-再灌注30、90、180min与缺血前比较,血MDA和CPK含量升高,SOD含量下降。治疗组缺血-再灌注同时间,血MDA含量明显低于对照组（P〈0.01）;CPK值低于对照组（P〈0.05）;SOD活性逐渐上升,180min高于对照组（P〈0.05）。结论七叶皂苷素有抗脂质过氧化作用,降低CPK值,提高SOD活性,能有效防治肢体缺血-再灌注损伤。     

急性黄磷中毒大鼠肝脏的脂质过氧化与肝损害的关系

本研究以黄磷3,6和9mg/kg ig,观察大鼠3,6,12和24h急性中毒时肝脏发生脂质过氧化程度、部位,以及与肝损害之间的关系。结果发现中毒大鼠肝匀浆、肝线粒体与微粒体MDA含量显著升高。肝匀浆Schiff碱荧光强度显著增强。肝线柱体与微柱体各自的标志酶SDH酶与G-6-P酶活性均显著降低,而且两亚细胞器的MDA含量升高与各自标志酶活性降低存在显著的负相关。肝TG含量显著升高与肝GSH含量显著降低的肝损害指标变化与脂质过氧化指标变化存在一定的平行关系。     

金丝桃甙对心肌脂质过氧化的影响

用ＴＢＡ法测定丙二醛（ＭＤＡ）含量，观察金丝桃甙（Ｈｙｐ）对阿霉素以及缺氧／再灌注所致心肌脂质过氧化的影响。结果表明：Ｈｙｇ１００ｍｇ·ｋｇ－１和ＥＧＴＡ４００μｍｏｌ·ｋｇ－１ｉｐ可明显抑制阿霉素所致小鼠心肌ＭＤＡ含量的升高，ＨＰＰ可增强ＥＧＴＡ的作用，Ａ２３１８７拮抗Ｈｙｐ的作用。ＨｙＰ１０、１００μｍｏｌ·Ｌ－１可显著减少缺氧；再灌注离体大鼠心脏ＭＤＡ的产生。提示Ｈｙｐ具有抗心肌脂质过氧化的作用，此作用可能与其阻滞钙内流有关。     

脂质过氧化对肾病患儿血液流变学的影响

本文观察了40例原发性肾病综合征患儿极期血清LPO与血液流变学各指标的变化及其二者的关系,结果表明:血清LPO显著增高,血液流变学明显异常,呈高凝状态改变。且二者呈明显正相关,逐步回归方程为Y=0.2119 0.9005x(1)。     

绞股蓝在大鼠肝的抗脂质过氧化作用

目的：观察绞股蓝（GP）对四氯化碳（CCl4)所致肝脏脂质过氧化的干预作用。方法：将Wistar大鼠随机分为4组：A（对照组）;B（CCL4）;C（GP);D(CCL4＋CP）。结果：CCL4组的脂质过氧化物（LPO）含量明显高于对照组,谷胱甘肽过氧化物酶（GSH－Px）活性低于对照组;而同时给予GP的D组可减弱CCL4诱发的上述作用。结论：GP能减弱CCL4对肝脏的损害。     

In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems in different models of gastrointestinal injury

1. The in vivo effects of the non-steroid anti-inflammatory drug (NSAID) amtolmetin guacyl (AMG) on lipid peroxidation (LP) and on antioxidant enzyme and non-enzyme defence systems were investigated in models of stomach and colon damages, induced by other NSAIDs, by ethanol or by 2,4,6-trinitrobenzenesulfonic acid (TNBS). 2. Indomethacin increased LP, glutathione peroxidase (GSH-PX) and glucose-6-phosphate dehydrogenase (Glu-6-P-DH) activities and decreased glutathione levels in gastric mucosa. Pretreatment with AMG normalized some of the parameters affected by indomethacin. 3. Treatment of rats with ethanol for 0.5 h led to a decrease in glutathione levels as well as activities of glutathione reductase and Glu-6-P-DH in gastric mucosa. AMG, administered 0.5 h before ethanol, limited the adverse actions of ethanol. 4. Amtolmetin guacyl failed to abolish the TNBS-induced changes in the followed-up parameters in colon mucosa and liver, but additional alterations (as with tolmetin) were not observed. 5. The beneficial profile of AMG in the various experimental models of free radical-induced damage investigated in this study suggests the possibility that this drug might possess antioxidant activity.     

补硒与锌对梭曼中毒大鼠乙酰胆碱酯酶活力和抗氧化力的影响

目的　探讨抗氧化剂硒 (Se)和锌 (Zn)预防梭曼中毒的可能性。方法　雄性大鼠 4 0只 ,按体重随机分为正常对照组、染毒组、硒治疗组、锌治疗组。正常对照组和染毒组每日 5mL·kg- 1的生理盐水(NS)ig ;硒治疗组每日 1mg·kg- 1Na2 Se0 3的NS液ig和锌治疗组每日 4mg·kg- 1Zn(C6 H11O7) 2 的NS液ig ,共ig 9d。d 10除正常对照组外其余各组大鼠均sc 0 .9LD50 梭曼 ,2h后断头处死并取样 ,测定大鼠全血乙酰胆碱酯酶 (AChE)活性及血清、大脑、肝脏的超氧化物歧化酶 (SOD)活性、总抗氧化力 (T AOC)和一氧化氮合酶 (NOS)活性。结果　梭曼中毒大鼠后 ,染毒组大鼠全血AChE活性被明显抑制 ,血清、大脑、肝脏的SOD活性、T AOC显著下降 ,NOS含量明显升高 ,而硒和锌预防组大鼠对梭曼引起的AChE、SOD、NOS活性和T AOC变化明显减轻。结论　提示硒和锌对梭曼中毒有较好的预防作用     

抗结核药物的肝损害与脂质过氧化反应的关系

目的　研究常用抗结核药物致肝脏损害的机制 ,了解不同抗结核药物组合对肝脏脂质过氧化反应程度 ,分析抗结核药物对肝脏损害的机制。方法　健康成年SD大鼠 (清洁级 ) 5 6只 ,体重 2 5 0～ 3 0 0g ,雌雄各半 ,随机分为 7组。对照组 :生理盐水 ;H(INH)组 :异烟肼 ;R(RFP)组 :利福平 ;Z(PZA)组 :吡嗪酰胺 ;HR组 :异烟肼 +利福平组 ;RZ组 :利福平 +吡嗪酰胺组 ;HRZ组 :异烟肼 +利福平 +吡嗪酰胺组 (大鼠用药的常规剂量 :指每公斤体重人的常用剂量乘以 5 .5倍 )。标本制备 :根据各组的不同要求 ,进行大鼠一次性灌胃 ,10d后断头取血 ,分离肝脏 ,制备 10 %的肝组织匀浆。分别测定各组肝组织匀浆丙二醛 (MDA)、超氧化物歧化酶 (SOD)、谷胱甘肽 (GSH)改变。结果　肝组织匀浆MDA与对照组比较 ,R组增高差异显著 (P <0 .0 5 ) ;HR组、RZ组、Z组增高差异非常显著 (P <0 .0 1) ;与HRZ组、HR组、R组、RZ组比较 ,HRZ组增高差异显著 (P <0 .0 5 ) ;HR组、Z组、RZ组组间差异无显著性 (P >0 .0 5 )。肝组织匀浆SOD与对照组比较 ,R组降低差异显著 ( P <0 .0 5 ) ;Z组、HR组、RZ组降低差异非常显著 ( P <0 .0 1) ;与HR组、R组、RZ组比较 ,HRZ组降低差异显著 (P <0 .0 5 ) ;Z组、HR组、RZ组组间差异无显著性 (P >0 .0 5 )。肝     

T2毒素对大鼠红细胞膜脂流动性及脂质过氧化的影响

Ｔ２毒素对大鼠红细胞膜脂流动性及脂质过氧化的影响彭双清，杨进生（北京毒物药物研究所，北京１００８５０）Ｔ２毒素是倍半萜类两歧性分子，极易与膜发生作用［１］．它能抑制ＤＮＡ，ＲＮＡ和蛋白质的合成，引起ＤＮＡ单链断裂及多核蛋白体分裂，以及与巯基酶相结合［...     

Effects of methiocarb on lipid peroxidation and glutathione level in rat tissues

Methiocarb is an N-methylcarbamate insecticide used worldwide in agriculture and health programs. The aim of this study was to investigate the possible effects of methiocarb to induce lipid peroxidation (LPO) in tissues of male Wistar rats following single and repeated oral exposures. Animals were divided into six different groups, and methiocarb was administered by orally at doses 25, 10, and 2?mg/kg body weight for 1, 5, and 28 days, respectively. Liver, kidney, brain, and testis tissues were taken from the rats for the biochemical examinations. LPO and reduced glutathione (GSH) levels were determined in the tissues. LPO was significantly increased in liver, kidney, brain, and testis after 1-, 5-, and 28-day treatments of methiocarb. GSH levels were significantly increased in the 1-day period and significantly decreased in the 5- and 28-day periods in all tissues after methiocarb administration. It is concluded that methiocarb may induce LPO and produce disturbances on the GSH levels in liver, kidney, testis, and brain of rats. This suggests that methiocarb-induced toxicity may be associated with oxidative stress to cellular membranes. Further studies are required to better understand the role of oxidative stress on methiocarb-induced toxicity.     

硒对过氧化氢所致老龄大鼠红细胞溶血及脂质过氧化的影响

本实验给老龄Wistar雄性大鼠腹腔注射亚硒酸钠(30μg/kg)15d,观察硒对过氧化氢所致红细胞溶血及脂质过氧化的抑制作用。结果表明硒降低了过氧化氢对红细胞的溶血率,同时过氧化氢所致脂质过氧化作用明显减弱。     

海狗油对实验性大鼠脂肪肝的抗脂质过氧化作用

目的:探讨海狗油对实验性大鼠脂肪肝的抗脂质过氧化作用及抗脂肪肝的作用机制。方法:小剂量四氯化碳合并高脂饲料建立大鼠脂肪肝模型,7周后,模型组ig等体积橄榄油、阳性药组ig辛伐他汀4mg·kg-1·d-1、海狗油低(L)、中(M)、高(H)剂量组分别ig海狗油0.5,1.6,4.8g·kg-1·d-1,连续8周,正常大鼠作为空白组。测定血清和肝脏中的丙二醛(MDA)、游离脂肪酸(FFA)、超氧化物歧化酶(SOD)、肝细胞色素P450 2E1(CYP2E1)免疫组化表达水平及脂肪肝指标即肝TC、TG、肝重、肝脏系数和组织学检查。结果:海狗油各治疗组与模型组相比血清和肝组织的MDA、FFA含量显著降低,SOD活性升高,CYP2E1免疫组化表达减弱。与之相应,大鼠脂肪肝指标肝重减轻,TC、TG减少,组织学检查显示肝细胞脂变程度显著减轻。结论:海狗油可诱导抗氧化酶SOD的活性,清除过多的氧自由基,从而减轻实验性脂肪肝症状,具有抗脂质过氧化作用。