维生素E对乙醇性肝损伤大鼠肝线粒体SOD和MDA的影响

目的:研究维生素E在乙醇性肝损伤肝组织亚细胞水平上的作用。方法:采用乙醇性肝损伤大鼠模型,测定乙醇灌胃及其VitE处理后肝线粒体SOD、MDA。结果:乙醇灌胃后肝线粒体SOD下降,而MDA上升;维生素E处理后SOD明显上升,MDA下降。结论:VitE可使乙醇性肝损伤大鼠肝线粒体SOD、MDA趋向正常,有抗氧化作用。     

维生素C,E对氟中毒大鼠肝、肾、脑组织形态学变化的干预作用

目的 探讨过量氟对实验大鼠肝、肾、脑的损害及维生素C,E的影响.方法 将120只Wistar大鼠随机分为9组,经饮水投氟建立氟中毒动物模型,并灌胃补充维生素C,E,9个月后处死大鼠,利用光镜观察氟中毒大鼠肝、肾、脑的形态学变化以及维生素C,E干预的影响.结果 氟中毒各组大鼠肝、肾、脑出现明显的组织形态学改变.肝组织的变化最为明显,表现为肝细胞水肿和点状坏死及汇管区炎性细胞浸润.肾脏以肾小球毛细血管扩张和肾小管上皮细胞水肿及肾间质出血为主要改变.脑神经胶质细胞增殖、水肿及间质血管扩张伴出血和炎性细胞浸润.维生素C,E单独干预组肝、肾、脑组织因氟中毒而发生的形态学改变均较染氟组轻.维生素C,E联合干预组各组织的形态学变化均比单独干预组轻.结论 过量氟引起大鼠肝、肾、脑组织不同程度的损害,经维生素C,E干预对过量氟引起的大鼠各组织损害有明显的拮抗作用,其中联合干预效果较为明显,干预效果与干预剂量和氟中毒损害的靶器官有关.     

维生素E和硒对CCl4大鼠急性肝损伤和抗氧化功能的影响

氧应激在急性肝损伤的发生过程中具有重要作用，因此提高机体的抗氧化功能对防治急性肝损伤具有重要意义。目的：探讨维生素E（Vit E)和硒对CC14大鼠急性肝损伤和抗氧化功能的影响。方法：48只健康雄性SD大鼠随机分为6组，每组8只。干预组第1周和第2周以及造模组第1周和第2周采用腹腔注射50％CC14和橄榄油混合制剂的方式建立大鼠急性肝损伤模型，干预组在饲料中添加Vit E (250mg/kg饲料）和硒（0.2mg/kg饲料）进行营养干预，造模组喂饲标准饲料；对照组第1周和第2周腹腔注射生理盐水，喂饲标准饲料。第1周和第2周组大鼠分别于处理1周和2周后处死，分别检测各项肝损伤指标和抗氧化指标，并观察其含量变化。结果：对于急性肝损伤大鼠，补充适量的Vit E和硒能降低血清丙二醛（MDA）水平，干预组的血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）升高幅度明显较造模组小，肝组织羟脯氨酸含量亦相对低于造模组。造模组的肝组织和血清硒水平在第2周明显升高，而Vit E水平显著降低，并伴随着超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）活性的显著升高，而干预组的各项指标基本维持不变。结论：CC14致大鼠急性肝损伤时，机体对抗氧化营养素的需求明显上升，补充Vit E和硒后，机体拮抗氧应激所致急性肝损伤的能力增强。     

维生素E对大剂量维生素D3所致心肌损伤保护作用的实验性研究

目的：观察大剂量VD3对心肌的损伤作用及维生素E（VE）对其保护机制。方法：Wistar大鼠36只随机分为3组,VE＋VD3组经口灌胃VE油剂8．3mg／（kg·d）,共7次,后3次给药加VD3油剂15万IU／只。VD3组同法给予生理盐水和VD3,对照组给予生理盐水。测定血清、心肌中的钙含量,血清中VE含量,测量血清、心肌和肝脏中谷胱甘肽过氧化物酶（GSH—Px）和脂质过氧化物酶（丙二醛,MDA）含量。测量心肌损伤面积。结果：VD3组血清中VE含量,血清、心肌和肝脏中GSH—Px活性明显低于VE＋VD,组和对照组（P〈0．01）,VE＋VD3组略高于对照组,但无显著性差异（P〉0．05）。VD3组血清、心肌、肝脏组织中MDA,血清、心肌钙水平明显高于VE＋VD3组和对照组（P〈0．01）,VE＋VD3组与对照组相比差异不显著（P〉0．05）。VE＋VD3组心肌坏死面积明显小于VD3组（P〈0．05）。结论：预先给予天然VE能保护大剂量VD3所致大鼠心肌损伤。     

当归对实验性肝损伤小鼠的抗自由基损伤作用

采用当归(20～40g/kg/d,ig×4d)治疗D-氨基半乳糖急性肝损伤小鼠,结果发现小鼠肝损伤明显减轻,血浆、肝匀浆过氧化脂质(LPO)、血浆丙二醛(MDA)含量下降,血清谷丙、谷草转氨酶(ALT、AST)降低。降低程度与用药量呈明显的量效关系。     

VE、VC对大鼠肝、心组织中谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化脂质的影响

本实验研究选用14个月龄Wistar大白鼠,研究了VE、VC单独摄入与二者联合摄入后对谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)和过氧化脂质(LPO)的影响。结果表明,无论单独饲喂VE、VC或二者联合使用,肝LPO均低于对照组,差异非常显著。大剂量VC降低LPO的作用明显大于VE组。从GSH-Px和SOD的变化来看,VC具有明显提高GSH-Px和SOD活性的作用,与降低LPO的作用一致。     

病毒性肝炎患者血浆LPO,VitE及红细胞SOD水平与肝功能的关系

检测45例病毒性肝炎患者血浆LPO,VitE及红细胞SOD水平,发现急性肝炎组、慢活肝组、重症肝炎组及肝硬化组血浆LPO值分别为5.52±2.6、9.67±5.11、18.22±6.81和7.51±5.051mmol/L.均明显高于正常对照组2.77±0.67(P<0.05),重症肝炎组升高最明显。血浆VitE值分别为9.22±3.83、7.81±2.67、6.56±2.64和6.99±2.67μmol/L,均明显低于正常对照组13.95±4.80(P<0.001),重症肝炎组下降最明显。4种肝病红细胞SOD水平与正常对照组比较无明显改变(P>0.05)。LPO增多、VitE减少与肝功能损伤程度一致。     

Effect of Alcohol Use on Allograft Rejection Rates after Liver Transplantation for Alcoholic Liver Disease

Alcoholic liver disease is a major cause of liver disease and has become an ever-increasing indication for liver transplantation (LTx). Follow-up studies have reported a higher rate of alcohol recidivism in patients transplanted for alcoholic hepatitis, compared with those transplanted for endstage alcohol-associated cirrhosis. It is assumed widely that recurrent alcohol use is associated with reduced compliance with immune suppression and, as a result, an increased risk of graft rejection and loss. To assess this question, 209 alcoholic patients transplanted for either alcoholic hepatitis with cirrhosis or cirrhosis alone between January 1, 1986 and December 31, 1991 were followed, with a mean follow-up of 4.4 ± 0.6 years. There were 175 episodes of acute cellular rejection (ACR) that occurred in 137 patients, for an overall rejection rate of 83.7% or at a rate of 1.25 episodes/patient with rejection. The rate of ACR was three times as great in those who remained alcohol-abstinent (2.24 episodes/patient), compared with those who admitted to continued alcohol use (0.75 episodes/patient) ( p < 0.01). A total of 33 episodes of chronic rejection occurred in 26 patients, for an overall rate of 12.4%. As was the case for ACR, the chronic rejection rate was greater among those who were continuously alcohol-abstinent, compared with those who intermittently used alcohol after successful LTx.
There were no differences in the mean FK 506 or cyclosporin A levels in the groups with and without a rejection episode at the time the rejection episode was documented by liver biopsy. Contrary to generally accepted opinion, these data suggest that continued use of alcohol by liver transplant recipients is associated with a reduction, not an increase, in the rate of rejection.     

Effect of Chronic Ethanol Feeding on Hepatic and Extrahepatic Distribution of Vitamin E in Rats

The effect of chronic ethanol feeding on the status of alpha- and gamma-tocopherol in plasma, liver, lung, and testes of Sprague-Dawley rats was characterized. Rats were pair-fed liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates. After 3 weeks, ethanol ingestion resulted in a significant (p less than or equal to 0.05) increase in liver weight and induced fatty liver without affecting total body weight. Ethanol feeding did not affect the plasma concentration of alpha-tocopherol but doubled that of gamma-tocopherol. When expressed per milligram of tissue, liver alpha-tocopherol did not vary with ethanol ingestion, whereas gamma-tocopherol concentration increased 2.5 times that of control animals. However, the concentration of alpha-tocopherol expressed per milligram of total lipids was significantly (p less than or equal to 0.01) decreased in the liver with ethanol feeding. In contrast to the liver, ethanol feeding significantly increased alpha- and gamma-tocopherol levels per milligram of total lipids in the testes. The concentration of gamma-tocopherol (but not alpha-tocopherol) per milligram of lung tissue and per total lung was significantly (p less than or equal to 0.05) increased with ethanol feeding. These data indicate that chronic ethanol ingestion significantly alters the distribution of alpha-tocopherol and gamma-tocopherol in hepatic and extrahepatic tissues of the rat.     

低硒环境下蛋氨酸对大鼠体内维生素E,硒及脂质过氧化物含量的影响

用低硒、低蛋氨酸饲料喂养大鼠8周后发现大鼠血清、肝脏及心肌中脂质过氧化物含量显著升高,血清维生素E显著下降,而心肌硒含量却显著升高。实验结果表明,在低硒环境下如降低饲料中蛋氨酸水平将导致大鼠体内脂质过氧化反应加剧。     

硒和维生素E对实验性肝纤维化的协同保护作用

目的：观察硒(Se)和维生素E(Vit．E)单独应用和联合应用对肝纤维化的影响。方法：以40％ CCl4制备大鼠肝纤维化模型,分别以单纯和联合补充Se和Vit．E的形式,观察血清肝功能指标(ALT、AST、Glb)、肝纤维化指标(HA)、抗氧化指标(SOD)和肝脏组织学变化。结果：单纯补充Se或Vit．E能够降低大鼠血清ALT、AST和Glb的含量,减轻肝细胞变性及肝纤维化增生程度,对SOD活性无显著性影响,单纯补充Vit.E能降低HA水平。联合补充Se和Vit．E对以上指标均有明显改善,且能显著提高SOD活性。结论：Se和Vit．E联合应用优于单一应用,二者具有协同保护效应。     

Manipulation of Alcohol Drinking by Liver Transplantation

The procedure of liver transplantation in alcoholic liver disease raises the question whether it would be possible to regulate the recipient's future drinking by the choice of donor liver. To address this question, we conducted transplantations with rat lines selected for high (AA) and low (ANA) alcohol preference. AA recipients having alcohol experience before the operation remained heavy drinkers regardless of whether the graft came from an AA or ANA donor. However, in those AA recipients who started drinking only after the operation, differences emerged, with AA grafts creating heavy drinking and ANA donor livers resulting in very low drinking. An overall increase in the acetaldehyde levels was introduced by the ANA livers, thus reflecting the original line differences. Similarly, in subsequent experiments, it was observed that when the aldehyde dehydrogenase inhibitor calcium carbimide was introduced in different amounts to the diet, alcohol drinking was reduced more in animals not used to drinking. The magnitude of this effect, especially in situations with established heavy drinking, is of relevance in future contemplations about liver transplantations between humans with dfferent aldehyde dehydrogenase genotypes.     

平脂冲剂对实验性脂肪肝的防治作用及病理图像分析

目的:观察平脂冲剂对高脂饲料造模大鼠脂肪肝病理形态和生化指标的影响以证实其疗效。方法:在常规组织学现察的基础上,利用计算机病理图像分析系统对改良锇酸染色脂滴进行多参数定量检查;并测定肝脏过氧化脂质含量和肝脂含量。结果:用改良锇酸染色方法,脂滴较常规HE染色更为清晰。平脂冲剂能使脂滴数量减少、面积缩小,肝/体比值亦缩小;可有效抑制肝组织过氧化脂质。结论:平脂冲剂可明显阻止和改善大鼠肝脏脂肪变性,对脂肪肝有良好的预防和治疗作用。     

Chronic Ethanol and Cocaine-Induced Hepatotoxicity: Effects of Vitamin E Supplementation

The mechanisms of chronic cocaine toxicity and its potentiation by ethanol were investigated. Cocaine was administered to male C57BL/6 mice (20 mg/kg by peritoneal injection twice a day) alone or in combination with ethanol-containing diets (26% of total calories) supplied with a normal (20 IU/liter) or high content (170 IU/liter) of vitamin E. Liver levels of vitamin E, reduced glutathione, ascorbic acid, and hydroxyproline were measured. Accumulation of thiobarbituric acid-reactive substances, after in vitro stimulation of lipid peroxidation by Fe3+/ADP/ascorbate system, was measured as an index of susceptibility of hepatic membranes to oxidative stress. Plasma alanine aminotransferase, lethality, liver weight, and liver/body weight ratio were determined to assess the extent of liver toxicity. Consumption of ethanol exacerbated liver toxicity induced by cocaine treatments and reduced survival, but ethanol or cocaine treatments alone caused no or only modest mortality. Ethanol potentiated cocaine-induced accumulation of collagen in the liver and depletion of ascorbic acid. Hepatotoxicity induced by the combined ethanol plus cocaine treatment was not accompanied by a decrease in intracellular vitamin E or glutathione content. There were no changes in the basic levels and in the rate of accumulation of thiobarbituric acid-reactive substances in liver homogenates under the lipid peroxidation-stimulating system in vitro. The toxic effects of ethanol and cocaine were not reduced by the ingestion of vitamin E during short-term exposure of 21 days of treatment.     

Formation of Reactive Oxygen Species in Lung Alveolar Cells: Effect of Vitamin E Deficiency

Reactive oxygen species (ROS) play an important role in the pathogenesis of numerous pulmonary diseases. Various mainly membrane-bound ROS-generating processes exist in alveolar cells. Vitamin E (vit. E) is the most important lipophilic antioxidant. However, the significance of vit. E levels in alveolar cells for the regulation of ROS generation has not been investigated so far. We demonstrated here that feeding rats with vit. E-depleted nourishment for 5 weeks reduced the concentration of vit. E in alveolar type II cell preparations to one-fifth the amount of control animals. This reduction of vit. E levels was associated with an approximately threefold increase in ROS generation in type II pneumocytes, lymphocytes, and macrophages. The contribution of individual processes of ROS formation in control animals differed strongly among these three cell types. However, vit. E deficiency induced predominantly nonmitochondrial ROS formation in alveolar cells. Expression and NAD(P)H-oxidase activity in alveolar type II cell preparations was not affected by vit. E deficiency. Moreover, protein kinase C (PKC) also did not seem to be responsible for vit. E deficiency-induced ROS generation in alveolar cells. Alimentary vit. E supplementation for 2 days corrected the cellular vit. E concentration but failed to normalize ROS generation in alveolar cells. These data let us assume that alimentary vit. E deficiency caused a preferentially nonmitochondria-mediated increase of ROS formation in type II pneumocytes, macrophages, and lymphocytes. However, the short-term supplementation of vit. E does not reverse these effects. R. Sabat and F. Guthmann contributed equally to this work.     

Prevention of Peritoneal Adhesions by Intraperitoneal Administration of Vitamin E: An Experimental Study in Rats

PURPOSE Previous studies have shown dietary supplements of vitamin E to reduce the incidence of postoperative peritoneal adhesions. The objective of this study was to show the effect of intramuscular or intraperitoneal administration of vitamin E on peritoneal adhesions.METHODS Eighty rats were divided into four groups: Group A (control), Group B (intramuscular vitamin E), Group C (intraperitoneal olive oil, the vehicle/diluent of vitamin E), and Group D (intraperitoneal vitamin E diluted in olive oil). The same experimental method was used in all rats to produce adhesions, consisting of cecal abrasion and ligature of the adjacent parietal peritoneum. The rats were killed at 14 days to assess the adhesions occurring. The results were analyzed using a chi-squared test.RESULTS All animals in Groups A, B, and C had substantial adhesions. In Group D, 11 rats had insubstantial adhesions and only 4 had substantial adhesions. There were no significant differences between Groups A, B, and C in terms of percent formation of adhesions. A significant difference was found between Group D (vitamin E plus olive oil by the intraperitoneal route) and each of the experimental groups, A, B, and C (P < 0.0005).CONCLUSIONS Our results show that intraperitoneal administration of vitamin E just before closing the laparotomy was effective for reducing adhesion formation. By contrast, the same effect was not achieved after intramuscular administration.     

维生素E对大剂量维生素D3所致心肌损伤的保护作用

本实验以大剂量维生素Ｄ３作为条件因素建立动物心肌损伤模型，观察维生素Ｅ对心肌损伤的保护作用。结果，大剂量维生素Ｄ３能降低大鼠心肌呼吸酶（细胞色素氧化酶和琥珀酸脱氢酶）活性。明显降低血清维生素Ｅ含量，使大鼠血清、心肌、肝脏组织谷胱甘肽过氧化物酶（ＧＳＨ—Ｐｘ）活性降低，脂质过氧化物（ＭＤＡ）含量升高。而预先给维生素Ｅ，能明显提高大鼠血清维生素Ｅ含量，提高呼吸酶活性．增强大鼠血清。心肌、肝脏组织ＧＳＨ—Ｐｘ活性，降低脂质过氧化物值。使大鼠心肌坏死面积明显减少。     

Liver Regeneration Attenuates Increased Voluntary Alcohol Intake Evoked by the Liver Damage

Liver dysfunction induced in Wistar rats either surgically (by construction of portocaval anastomosis) or chemically (by chronic administration of thioacetamide) led to increased voluntary alcohol intake. Alcohol preference could be attenuated by liver regeneration that was triggered by a two-thirds hepatectomy done on cirrhotic rats. The brain serotonin system was activated in portocaval anastomosis rats and unchanged in thioacetamide-treated rats, thus suggesting that serotonin is not likely to be implicated in the mecha-nism(s) underlying development of alcohol preference in these rats. Also, tetrahydro-p-carboline could possibly be excluded from consideration. Neither change in the brain concentration or distribution of tetrahydrobetacarboline after long-term treatment with thioacetamide could be found.     

Chronic Alcohol Administration Stimulates Nitric Oxide Formation in the Rat Liver With or Without Pretreatment by Lipopolysaccharide

This study examines the effect of chronic alcohol consumption on nitric oxide release from the liver of rats with or without lipopolysaccharide (LPS) (Escherichia coli) treatment. Reactive nitrogen intermediates (RNIs) in plasma were monitored with an NO_x Analyzer, and nitric oxide (NO) production was measured as nitrite or nitrite + nitrate accumulation in perfusates of the perfused liver, and in supematants of the freshly isolated hepatic cells after incubation for 3 hr in Hank's balanced salt solution buffer containing 1 Mm l -arginine. RNI concentration in plasma of control rats was 32.0 ± 3.4 μm (mean ×se ). Livers from diet-fed control rats produced RNIs at the barely detectable rate of 7.8 ± 1.5 nmol/hr × g wet liver. Six hr after administration of LPS (1 mg/kg, iv), plasma RNI levels in diet-fed control rats increased to 426.9 ± 29.4 μm , and RNI release from the perfused liver was also markedly elevated to 97.7 ± 7.7 nmol/hr × wet g liver, indicating hepatic NO release as a potentially important source for the increased RNI in plasma. The presence of N^G-monomethyl-l -arginine (0.5–1 mm ) or the absence of l -arginine in the perfusate inhibited LPS-induced stimulation of RNI release. EGTA (1 mm ) had little effect, indicating that the increased RNI release was likely to be due to inducible NO synthase activity. The release of RNIs by freshly isolated Kupffer cells increased 13-fold, and this small cell mass contributed almost half of the hepatic RNI production under these conditions. Plasma ALT concentration was elevated after LPS administration, indicating incipient liver damage. Chronic alcohol administration resulted in increased RNI levels in plasma (44.6 ± 4.2) that were accompanied by increased spontaneous release in the perfused liver (16.4 ± 1.5 nmol/hr wet g). Enhanced activity of Kupffer cells was responsible for this increase. After administration of LPS, the increase in plasma RNIs (565.72 ± 49.6 μm ) was slightly higher in chronic alcoholic rats than in control animals. This was also accompanied by a somewhat higher RNI release from the perfused liver (125.40 ± 12.2 nmol/hr × wet g) in the same group. Hepatocytes were responsible for the post-LPS increase in alcoholic rats. Plasma ALT concentration was higher in alcoholic than control, diet-fed rats after LPS, indicating more liver damage in that group. The exact role of the elevated hepatic RNI release in affecting hepatic function in chronic alcoholic animals remains to be clarified.