肝脂类水平与脂质过氧化指标的多元相关分析

肝脂类水平与脂质过氧化指标的多元相关分析林育纯１林忠宁肝脏是机体脂类代谢的重要器官，肝细胞损伤可致肝脂类水平改变。近年研究表明，脂质过氧化作用是引起许多疾病和损伤的分子病理基础，抗氧化作用维护机体正常的功能［１］。但有关肝脂类代谢与氧化－抗氧化作用的...     

TNT影响肝脏混合功能氧化酶的规律

利用大鼠苯巴比妥诱导条件下急性和亚急性实验模型,以肝微粒体细胞色素P-450含量、氨基比林脱甲基酶活性、苯胺羟化酶活性和脂质过氧化水平为指标,进一步探讨不同剂量、不同时间TNT染毒对肝脏MFO影响规律及TNT改变MFO活性的可能机理。急性染毒时,各剂量组动物肝脏MFO功能均表现抑制,呈明显剂量反应关系;TNT对MFO抑制的酶谱较广,P-450含量、脱烷基功能和羟化功能均受影响。亚急性染毒见P-450含量与MFO代谢活性的改变同步,呈先诱导后抑制的双相效应,继而可表现“钝感”。TNT可在活体大鼠引起肝微粒体脂质过氧化,过氧化强度与MFO抑制程度经统计分析高度相关。本文扼要讨论了上述结果。     

工业毒物与肝脏混合功能氧化酶的相互影响

为探讨工业毒物与肝脏混合功能氧化酶（ＭＦＯ）的相互影响规律，从中寻找对人体影响的监测依据，进行了实验研究与现场研究。结果发现：在各种实验染毒条件下，不同毒物可导致ＭＦＯ活力的多样化改变：诱导或抑制、单相或双相反应等，毒物毒性可随之改变；ＭＦＯ还参与多种毒物代谢，与多种肝毒机制有关，如脂质过氧化作用、肾上腺皮质功能改变及肝细胞大分子共价结合作用等，其中人体ＭＦＯ对毒物的反应规律，有望提供肝脏毒物对人体影响的监测指标。     

125泛酸在脂肪酸代谢中的作用

泛酸是辅酶Ａ（ＣｏＡ）的前体，ＣｏＡ是其发挥功能的生物活性形式，在含碳架物质产生能量及许多细胞结构的形成中均需泛酸参与。摄食不足或生理状态的改变可引起泛酸缺乏。泛酸缺乏使需要ＣｏＡ的反应受到抑制，主要影响脂肪酸代谢，使脂肪酸β－氧化受到抑制，特别是过氧化物酶体中的脂肪酸氧化显被抑制，可导致高血脂等，严重可产生脑部损害。另外，泛酸尚具抗脂质过氧化作用，对遭受脂质过氧化损伤的细胞和大鼠具有很好的保     

镉对大鼠肝、肾微粒体脂质过氧化反应的影响

镉是一种重要的工业毒物,其进入机体后,可对人体产生多种损害作用,其中,肝和肾是镉作用的主要靶器官。有文献报道镉能明显抑制肝、肾微粒体生物转化酶的活性,从而使毒物在体内的代谢过程受到干扰。因此,为了进一步探讨镉对肝、肾生物转化过程抑制的机理,本文在体内和体外试验中,较为系统地研究了镉对肝、肾微粒体脂质过氧化(LPO)反应的影响。     

毒害物质与人体脂质过氧化的关系(综述)

脂质过氧化是近年来发展起来的重要中毒机理学说，它可引起各种生物膜的损伤。谷胱甘肽-S-转移酶(GST)是二相反应的重要酶系，催化具有亲合位点的谷胱甘肽(GSH)，与多种亲电子物质、致癌物、亲脂性化学物质结合，参与细胞代谢解毒，清除自由基。随着自由基学说的发展对脂质过氧化作用的研究不断深入，现就人体受几种毒害物质作用引起脂质过氧化变化加以概述。     

DNA氧化损伤与肿瘤

氧化应激或脂质过氧化造成的DNA氧化损伤是肿瘤发生的重要致病机理.本文对氧化应激或脂质过氧化诱发的DNA氧化损伤及其检测方法,以及DNA加合物作为氧化应激或脂质过氧化生物标志物在肿瘤病因学和预防研究中的应用作简要概述.     

黄磷与四氯化碳亚急性肝损害的机理

本文研究黄磷与CCl_4引起亚急性肝损害时,肝脏发生脂质过氧化的情况、部位及其与肝损害之间的关系。黄磷与CCl_4对大鼠亚急性中毒时,肝MDA 含量显著升高,Schiff 碱荧光强度明显增强;肝线粒体与微粒体MDA含量显著升高,且各自标志酶SDHase 活性与G-6-Pase 活性均显著降低;肝损害指标:肝TG 含量升高对两种毒物均敏感;而肝GSH 含量降低与血清SGPT 酶活性升高对两种毒物的敏感性有一定的差异。     

四氯化碳引起大鼠肝微粒体钙泵的抑制与巯基关系的探讨

四氯化碳（ＣＣｌ４）与肝微粒体共同温浴，引起微粒体的丙二醛（ＭＤＡ）升高、蛋白巯基的降低和钙泵的抑制。与对照组比较具有显著性意义，且存在着剂量－反应关系及时间－反应关系。在本实验条件下，发现Ｃｌ４引起蛋白巯基的降低和钙泵的抑制呈明显的相关关系。用巯基供剂ＤＴＴ、过化物自由基清除剂ＳＯＤ均能部分地拮抗ＣＣｌ４引起肝微粒体脂质过氧化（ＬＰＯ），从而保护了微粒体的蛋白巯基及钙泵。表现耿ＤＴＴ＋ＣＣｌ４及     

防治肝病，从补硒开始

国内外大量研究表明．硒与肝脏疾病的发生、发展及预后关系密切。在硒有效防治肝炎、肝硬化的作用下,肝癌也得到了较好地防治。一、肝炎肝炎产生的病因最常见的是肝炎病毒,此外还有酗酒及自身免疫病等。病毒性肝炎发生的重要分子病理学基础是自由基及其引发的脂质过氧化反应。国外学者证明,血清硒是一种抗肝坏死保护因子．缺乏时可使肝硒含量下降．肝代谢功能紊乱,产生过氧化损害及氧化坏死。     

Copper and selenium deficiencies do not enhance the cardiotoxicity in rats due to chronic doxorubicin treatment.

This study tests the hypothesis that Cu and Se deficiencies enhance doxorubicin-induced cardiotoxicity and anemia. Male Sprague-Dawley rats (n = 48) were fed Cu and Se-adequate (+Cu+Se), Cu-deficient (-Cu), Se-deficient (-Se) or Cu and Se-deficient (-Cu-Se) diets for 5.5 wk. Doxorubicin (4 mg/kg body wt) or saline was administered once weekly for the last 4 wk of the study. Copper deficiency was confirmed by 79% lower liver Cu, 67% lower liver Cu,Zn superoxide dismutase (Cu,Zn SOD) activity and 76% lower erythrocyte Cu,Zn SOD activity. Selenium deficiency was confirmed by 90% lower liver glutathione peroxidase activity. Rats fed the -Cu diet had greater reductions in hematocrit than did those fed the +Cu diet after administration of doxorubicin. Doxorubicin, Cu deficiency and Se deficiency all produced electrocardiographic abnormalities and ultrastructural anatomical lesions. However, the dietary deficiencies did not enhance doxorubicin-induced cardiotoxicity. Doxorubicin, but not Cu or Se deficiency, raised lipid peroxidation 16% in liver (P < 0.01) and 18% in heart (not significant). These data suggest that the cardiomyopathies caused by doxorubicin and Cu and Se deficiencies have some similarities, but cardiac changes may be related to mechanisms other than lipid peroxidation.     

Effect of zinc and copper deficiency on microsomal NADPH-dependent active oxygen generation in rat lung and liver

Both dietary zinc and copper deficiencies can cause lipid peroxidation in microsomes in rats. The cytochrome P-450 enzyme system can generate active oxygens by uncoupling of the P-450-oxy complex in the catalytic cycle and/or the electron transfer mediated by the NADPH-cytochrome P-450 reductase. The effects of dietary zinc and copper deficiencies on NADPH-dependent H2O2 generation, the catalytic activity of the cytochrome P-450 enzyme with aminopyrine as the substrate and the activity of NADPH-cytochrome P-450 reductase were determined. Zinc deficiency caused increased H2O2 production, increased NADPH-cytochrome P-450 reductase activity, decreased aminopyrine demethylation and two- and fivefold increases in iron concentration in lung and liver microsomes, respectively, compared to Zn-adequate, ad libitum--fed controls. Active oxygen generation by uncoupling of the cytochrome P-450 enzyme system and accumulation of iron are thus possible mechanisms by which zinc deficiency causes microsomal lipid peroxidation. Copper deficiency did not affect H2O2 production; however, it caused two- and fourfold increases in iron concentration in lung and liver microsomes, respectively, compared to Cu-adequate, ad libitum--fed controls. The mechanism by which cooper deficiency causes microsomal lipid peroxidation is still unknown but could be related to the observed accumulation of iron.     

Lipid peroxidation and glutathione peroxidase activity in the liver of cholesterol-fed rats.

The effects of cholesterol feeding on lipid peroxidation and on glutathione peroxidase activity in the liver of rats were examined. Cholesterol (1 or 1.5%) was added to two basal diets containing either 10% soy oil (diet 1) or 15% soy oil plus 100 IU of alpha-tocopherol/kg of diet (diet 2). The rate of lipid peroxidation in the liver was determined in vitro by the thiobarbituric acid test and by conjugated diene measurement (234 nm). Cholesterol feeding elevated the rate of lipid peroxidation in the liver of rats fed diet 1 or 2. The rate of lipid peroxidation in rats fed diet 2 increased with duration of feeding suggesting an increased need for antioxidant as the levels of cholesterol or other lipids in the liver elevated. Cholesterol feeding also decreased the activity of liver glutathione peroxidase and pentose phosphate pathway dehydrogenases. Glutathione peroxidase activities increased with the duration of feeding in rats fed basal diet 2, but they remained unchanged in rats fed the same diet supplemented with cholesterol. The study suggests that cholesterol feeding in rats can increase the susceptibility of the tissue to lipid peroxidation and also can lead to a depression in the activity of glutathione peroxidase.     

Metformin improves liver antioxidant potential in rats fed a high-fructose diet

Increased lipid peroxidation plays a role in the pathology associated with fructose feeding. The present study reports the effects of metformin on the liver lipid peroxidation and antioxidant defence system of rats fed a high-fructose diet. The experimental animals were divided into two batches of 12 animals each. The control batch received a control diet containing 60% starch; the second batch was given a high-fructose diet containing 60% fructose as the sole source of carbohydrate. At the end of second week these were each subdivided into two groups. One was given metformin (50 mg/kg body weight/day in water) by intragastric intubation and the other group was left untreated. The rats were continued on the same dietary regimen for the next two weeks. After the experimental period of four weeks, liver lipid peroxidation and antioxidant status were quantified. Enhanced thiobarbituric acid-reactive substance reactivity and lipid hydroperoxides were observed in high-fructose-fed rats. However, the activities of enzymic antioxidants were lower in this group. Administration of metformin attenuated the rise in lipid peroxidation and improved the antioxidant potential in high-fructose-fed rats. Metformin did not have any effect on the antioxidant status of control rats. Attenuation of lipid peroxidation by metformin could be related to its insulin sensitising action.     

Tissue antioxidant status differs in spontaneously hypertensive rats fed fish protein or casein

The present study was designed to determine whether changes in dietary protein source are related to changes in antioxidant status determined by enzyme activities of catalase, superoxide dismutase (SOD), gluthatione peroxidase (GSH-Px) and gluthatione reductase (GSSG-Red) and lipid peroxidation levels in various tissues. Spontaneously hypertensive rats (SHR; 5 wk old) were fed diets containing 20% casein or fish protein for 2 mo. Feeding the fish protein diet lowered blood pressure and reduced plasma total cholesterol levels and SOD activity in all tissues except muscle compared with the casein diet. Feeding fish protein also enhanced GSH level and GSH-Px activity in liver and heart, accompanied by lower lipid peroxidation. In kidney, however, the lower catalase activity in rats fed fish protein was associated with an enhancement in lipid peroxidation. Plasma and VLDL + LDL lipid peroxidation was unaffected by dietary proteins. In conclusion, the fish protein diet did not play a relevant role in plasma antioxidative defense status but increased it in liver and heart compared with the casein diet. Fish protein attenuated the development of hypertension and also decreased plasma total cholesterol concentration. Thus, it enhances protection against cardiovascular diseases.     

高水平维生素E对大鼠血脂、肝脂及肝脂质过氧化的作用

采用成年Wistar大鼠为实验动物,雌雄各半。1组为基础饲料对照组,2组为高脂饲料对照组,3、4、5组分别以维生素E30、60、120mg/d灌胃,同时喂饲高脂饲料。实验8周后停止灌胃并改饲基础饲料5周至实验结束。 研究表明:1.高水平维生素E(60和120mg/d)对高脂饲料诱导的大鼠肝实质细胞中性脂肪蓄积及肝脏(体内)脂质过氧化的增加均有明显抑制作用。2.高水平维生素E(30、60和120mg/d)无明显降低大鼠血清胆固醇、甘油三酯及增加血清高密度脂蛋白胆固醇的作用。大鼠血清维生素E与胆固醇水平呈正相关关系,与高密度脂蛋白胆固醇无明显相关。提示维生素E可能并无抑制高脂血症的作用。3.喂饲高脂饲料时雌鼠血清胆固醇的反应比雄鼠敏感,维生素E灌胃时雌鼠血清维生素E的反应比雄鼠敏感,提示存在性别差异。     

Endotoxin and lipid peroxidation in vitro in selenium- and vitamin E-deficient and -adequate rat tissues

The effect of Salmonella typhimurium endotoxin injected intraperitoneally into rats (0.5 mg/kg of body weight) on subsequent lipid peroxidation in vitro was assessed. Peroxidation was monitored by measuring ethane production from tissue slices, as well as thiobarbituric acid-reactive substances and conjugated dienes in tissue homogenates. Weanling rats were fed a selenium- and vitamin E-deficient basal diet or one supplemented with 0.2 mg of Se/kg of diet and 200 mg of vitamin E/kg. After 9 to 16 wk, ethane production and thiobarbituric acid-reactive substances in liver and lung generally were increased by LPS treatment of Se- and vitamin E-deficient rats. Conjugated dienes were increased by LPS treatment in liver of Se- and vitamin E-deficient rats, but paradoxically, were higher in Se- and vitamin E-adequate liver tissue. Daily injections of 1 g of hydroxyurea/kg of body weight, a cell proliferation inhibitor, for 2 d prior to LPS injection significantly decreased the LPS-induced ethane production in Se- and vitamin E-deficient rat liver and lung. These results show that low doses of LPS injected into rats stimulated lipid peroxidation in vitro in Se- and vitamin E-deficient rat liver tissue. Hydroxyurea decreased LPS-induced lipid peroxidation in vitro; this suggests that neutrophils or macrophages are involved in LPS-induced lipid peroxidation.     

Accelerating effect of 12-keto oleic acid on lipid peroxide and fluorescent productions in mouse liver homogenate.

12-Keto oleic acid is generally considered to be a secondary degradation product of peroxides produced by lipid peroxidation. The acid was added to a mouse liver homogenate or to a bovine serum albumin and its influences on lipid peroxidation and fluorescent production were investigated and compared with other acids. Just as with vitamin E deficiency, 12-keto oleic acid was shown to increase lipid peroxide formation and fluorescence productiod directly and indirectly. The increase of lipid peroxide formation was caused directly through the increase of the free radical production, and indirectly through change of the biomembrane structure. The fluorescence production increase was caused directly by reaction of the 12-keto oleic acid itself, and indirectly by acceleration of the lipid peroxidation.     

Dietary supplements of vitamin E, beta-carotene, coenzyme Q10 and selenium protect tissues against lipid peroxidation in rat tissue slices

A tissue slice model was employed to assess the effects of dietary antioxidant supplements on lipid peroxidation. In one experiment, rats were fed diets containing, either alone or in combination, vitamin E, selenium, beta-carotene or coenzyme Q10 for 42 d, and the extent of spontaneous and induced lipid peroxidation was determined by release of thiobarbituric acid-reactive substances (TBARS) into the medium. Vitamin E exhibited the greatest protection against lipid peroxidation in liver, heart and spleen; in kidney, selenium was most protective. Coenzyme Q10 was active against lipid peroxidation induced by tertbutyl hydroperoxide (t-BHP). In a second experiment, rats were fed diets containing varying amounts of vitamin E, selenium, beta-carotene and coenzyme Q10 for 30 d. Spontaneous lipid peroxidation in liver, kidney and heart decreased with increasing levels of dietary antioxidants. With increasing amounts of antioxidants, there was a diminution in TBARS released by liver and kidney slices incubated with t-BHP; in heart, only the highest levels of antioxidants significantly decreased production of TBARS. Inverse correlations between dietary vitamin E and TBARS, tissue vitamin E and TBARS, and tissue selenium-glutathione peroxidase and TBARS were highly significant. The procedure used here can evaluate dietary supplements that may find practical applications in decreasing the oxidant radical portion of disease processes.     

Vitamin E inhibition of lipid peroxidation and ethanol-mediated promotion of esophageal tumorigenesis.

Promotion of chemically induced esophageal cancer by ethanol may include the generation of highly reactive free radicals and thus may be preventable by the antioxidant vitamin E. In the present study, female C57BL/6 mice received N-nitrosomethylbenzylamine (NMBzA, 0.2 mg/kg ig) three times a week for three weeks. After this esophageal carcinogenic treatment, mice were fed a nutritionally adequate liquid diet with 30% of the calories supplied by ethanol or an isocaloric carbohydrate with or without supplemental alpha-tocopherol (142 mg/kg diet). As a marker of in vivo lipid peroxidation, exhaled ethane was collected and measured 24 hours "before" the mice were killed after 20 weeks of dietary treatment. Hepatic malondialdehyde, lipid fluorescence, and conjugated dienes were determined as markers of products of lipid peroxidation and serum aminotransferases as indexes of liver toxicity. Hepatic liver concentrations of vitamins A and E and the size and frequency of esophageal tumors were also assessed. Ethanol consumption after NMBzA administration significantly increased (p less than 0.05) the size and frequency of esophageal tumors. These ethanol-promoted effects were accompanied by increases in indexes of in vivo and accumulated products of lipid peroxidation. Similarly treated animals that received supplemental dietary vitamin E showed significant reductions (p less than 0.05) in mean tumor size and frequency of tumors as well as a decrease in the indexes of hepatic lipid peroxidation. The results suggest that promotion of NMBzA-induced esophageal tumors by ethanol may in part result from increased lipid peroxidation and that vitamin E reduces carcinogenicity of NMBzA or ethanol promoter effects by inhibiting lipid peroxidation.