坏死性凋亡在乙醇诱导肝损伤机制中的作用研究进展

<正>乙醇滥用是目前全球关注的医学和社会问题。肝脏是机体重要的代谢器官,对体内外许多物质(药物、毒物及某些代谢产物等)具有生物转化作用。乙醇在肝脏代谢中氧化为乙醛、乙酸,其代谢产物是诱导肝损伤的主要因素。长期乙醇暴露可导致明显的肝损伤和组织重建,包括肝脂肪变性、肝炎、肝纤维化、肝硬化等病理改变,通常称之为乙醇性肝病,该 更多还原     

阿魏酸钠对乙醇损伤性大鼠肝切片的保护作用及机制

目的:采用精密肝切片技术,研究阿魏酸钠(SF)对乙醇损伤性大鼠肝切片的保护作用及机制。方法:制作大鼠乙醇损伤肝切片模型,观察不同浓度SF对切片培养液中肝损伤标志酶及胞浆苯胺羟化酶(ANH)、乙醇脱氢酶(ADH)活性的影响。结果:乙醇50mmol·L-1作用肝切片4h时,培养液中谷丙转氨酶、谷草转氨酶、乳酸脱氢酶和谷胱甘肽S-转移酶活性明显升高,同时肝切片胞浆ANH活性升高、ADH活性降低。当共处理SF463~1388nmol·L-14h后,培养液中各酶活性显著降低至正常水平,SF浓度增至694nmol·L-1以上时,肝切片胞浆ANH和ADH活性也恢复正常。结论:SF能有效拮抗乙醇所致的肝损伤,其机制与改变乙醇代谢途径有关。     

细胞色素P4502E1与乙醇代谢相关的肝损伤研究进展

近年细胞色素P450酶系中的2E1亚家族与乙醇相关的肝损伤研究结果进一步验证了CYP2E1酶在乙醇代谢中的关键作用。CYP2E1酶的多态性对乙醇导致肝损伤的影响包含该酶的代谢效率差异(C2/C2)>(C1/C2)>(C1/C1)造成不同程度的肝脏细胞损伤以及不同等位基因造成饮酒倾向的差异越来越受到关注。研究证实,多种物质尤其是中药材饮片及提取物可影响该酶含量及活性,从而保护肝细胞以及对乙醇损伤后肝脏细胞的修复。本文就近年来细胞色素P4502E1及其基因与乙醇相关的肝损伤研究进展做一综述。     

慢性乙醇中毒性周围神经病大鼠的氧化应激研究

目的 研究乙醇及其代谢产物的直接毒性作用所导致的大鼠坐骨神经氧化抗氧化平衡机制异常,以探讨慢性乙醇中毒性周围神经病的发病机制.方法 建立慢性乙醇中毒性周围神经病大鼠模型,在实验开始后第8,12,16周分别测定其坐骨神经的谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)值.结果 乙醇灌胃第8周乙醇组大鼠GSH、GSH-PX含量增加显著,MDA量无变化;灌胃第12周GSH量下降,GSH-PX继续增加,MDA无明显变化;灌胃第16周GSH继续下降,GSH-PX酶活力骤降,MDA量明显增加.结论 乙醇组大鼠坐骨神经中GSH,GSH-PX,MDA的动态变化反映了大鼠对乙醇损害的代偿性保护反应和最终抗氧化能力的降低导致了对组织的损害.     

乙醇摄入对小鼠肝功能及磺胺嘧啶代谢动力学的影响

动态观察了乙醇摄入对小鼠肝功能及磺胺嘧啶（ＳＤ）代谢动力学的影响。结果表明，每天以２５ｇ／ｋｇ乙醇摄入２周，ＳＧＳＴ活性明显升高，随着摄入时间的延长，在一定时间范围内呈进行性增高，同时，ＳＡＬＴ活性也与乙醇摄入时间呈明显正相关，提示长期乙醇摄入对肝脏的不利影响。乙醇对肝匀浆中ＧＳＴ和苯胺羟化酶活性呈双重作用，早期具有诱导酶活性的作用，但诱导的时间和强度不同，后期则可抑制酶的活性。ＳＤ在小鼠体内的代谢符合二房室模型，乙醇对ＳＤ的代谢具有双相作用，早期使ＳＤ代谢加速，后期则使代谢延缓，表明乙醇对代谢ＳＤ的Ｎ乙酰化酶可能具有酶促酶抑双重作用。     

浅谈不宜与乙醇合用的药物

患者在应用某些药物时不宜与含有乙醇的药品合用或饮用含乙醇的饮品。这是因为乙醇具有酶促作用,会加速一些药物在体内的代谢,降低这些药物的药效;反之有些药物也能影响乙醇的代谢过程,使乙醇或其代谢产物在体内堆积,产生不良反应。乙醇与一些药物具有协同作用,能增强其药理作用,加重其不良反应。1乙醇的酶促作用会降低药效乙醇是一种肝药酶诱导剂,能够使肝药酶的活性增强,加速苯巴比妥、苯妥英钠、安乃近、甲苯磺丁脲、胰岛素、双香豆素、华法令等药物的代谢,使这些药物的半衰期缩短,药效下降。2某些药物会影响乙醇的代谢过程(1)能够抑制乙…     

复方中药对乙醇性肝病的治疗机制研究

乙醇中毒性肝病现已成为仅次于肝炎病毒之后第二大肝病病因,乙醇通过多种途径作用而影响肝脏,导致乙醇性肝病的加重。本文综述了复方中药对乙醇性肝病的治疗作用,从加速乙醇代谢、减轻肝脏炎性反应、促进肝纤维化逆转3个方面阐述了中医药对乙醇性肝病的治疗机制,并提出当前研究中的某些薄弱点。     

虾青素对小鼠急性乙醇肝损伤的保护作用

目的:研究虾青素对乙醇所致小鼠急性化学性肝损伤的保护作用。方法:雄性小鼠60只,随机分为正常对照组、急性乙醇肝损伤模型组、联苯双酯阳性对照组(15 mg/kg)以及虾青素低、中、高剂量组(10,15,20 mg/kg)共6组。测定并比较各组小鼠肝脏系数,血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-px)活性与丙二醛(MDA)含量;测定肝组织中SOD,GSH-px活性,MDA含量以及组织病理系数。结果:各剂量虾青素均能升高急性乙醇肝损伤小鼠血清与肝组织中SOD,GSH-px活性(P<0.01),降低血清ALT,AST活性(P<0.01),降低血清与肝组织MDA含量(P<0.01),并能不同程度地改善肝脏病理组织损伤。结论:虾青素对乙醇所致急性肝损伤具有预防性保护作用。     

乙醇性肝病

乙醇性肝病是一有特异性病理生理改变的肝脏损伤。乙醇性肝病在组织病理学上主要表现为3种形式:乙醇性脂肪肝、乙醇性肝炎和乙醇性肝硬化。乙醇性肝病的发病机制尚不明确,但免疫机制和自由基损伤被认为起重要作用。乙醇性肝病的临床表现包括乏力不适,黄疸等。治疗的主要措施是戒酒、感染和门脉高压等并发症的处理、营养支持。     

乙醇与肝脏

乙醇对于人体来说是一种异物，这里所讲的乙醇代掰主要是指通过饮酒而摄人体内的外源性乙醇在体内的代谢。肝脏是乙醇代谢的主要器官，占所摄取乙醇的90％～98％，剩下的2％～10％随尿及呼出气而排泄。由于长期饮酒引起生化功能上的改变，易形成乙醇性脂肪肝、乙醇性肝炎、肝硬化甚至在孕妇可造成胎儿性乙醇综合症，影响胎儿生长发育，因此，了解乙醇在人体内的代谢及乙醇对肝脏的损害，在含酒精饮品日益泛滥的今天有重要的生理意义、临床意义和社会意义。     

Aspirin increases blood alcohol concentrations in humans after ingestion of ethanol

Gastric first-pass metabolism of ethanol is an important determinant of blood alcohol concentrations. We studied five healthy volunteers after ingestion of ethanol (0.3 g/kg of body weight) and found that blood alcohol concentrations in the fed state (ie, 1 hour after a standard breakfast) were significantly higher when the subjects received 1 g of aspirin 1 hour before ingestion of ethanol than without the drug. In vitro, aspirin clearly decreased the activity of gastric alcohol dehydrogenase in human subjects and in rat models, but not that of hepatic alcohol dehydrogenase in rats. Furthermore, blood alcohol concentrations in rats were unaffected by ingestion of aspirin when ethanol was infused intravenously. Thus, aspirin may increase the bioavailability of ingested ethanol in humans, possibly by reducing ethanol oxidation by gastric alcohol dehydrogenase.     

HepG2细胞系载脂蛋白B表达的调控研究

探讨白细胞介素－11（IL－11）及乙醇对人肝肿瘤细胞系（HepG2）载脂蛋白B（apoB）mRNA表达及蛋白分泌的作用。培养HepG2细胞,分组加入不同浓度IL－11进行浓度试验,收集培养液及细胞。用火箭电泳法及Northernblot分别检测培养液中apoB含量及HepG2细胞apoBmRNA的表达。IL－11及乙醇抑制试验按同法分组进行。结果IL－11能抑制HepG2细胞apoB表达与分泌,且呈量效正相关。IL－11能明显抑制乙醇的正向作用。说明IL－11能调节HepG2细胞apoBmRNA表达与分泌,可参与调节机体脂质代谢。     

Alcohol and acetaldehyde metabolism in Caucasians, Chinese and Amerinds.

Ethanol (0.4 to 0.8 g/kg in 30 minutes) was given by mouth to 102 healthy young volunteers (37 Caucasian men, 21 Caucasian women, 20 Chinese men and 24 Ojibwa men). Venous blood concentrations of ethanol and acetaldehyde 60, 90, 120 and 150 minutes after the end of drinking were measured by gas chromatography. The calculated rates of ethanol metabolism in the Caucasian men and women did not differ, but the overall group means for subgroups of Caucasians (103.6 mg/kg-h), Chinese (136.6 mg/kg-h) and Ojibwa (182.7 mg/kg-h) with decreasing postabsorption values differed significantly from each other. Mean acetaldehyde values paralleled the rates of ethanol metabolism: Ojibwa, 14.6 mug/ml; Chinese, 10.0 mug/ml; and Caucasians, 9.4 mug/ml. The high rate of ethanol metabolism in Amerind subjects differs from previous findings. Habitual level of alcohol consumption, proportion of body fat and genetic factors appear to account for most of the group differences.     

肾纤康颗粒乙醇渗漉工艺的研究

目的优选肾纤康颗粒乙醇渗漉工艺。方法以乙醇提取物中有效成分丹参酮ⅡA含量为指标,运用高效液相色谱,使用正交设计法,优选肾纤康颗粒乙醇渗漉工艺。结果肾纤康颗粒乙醇渗漉工艺为：乙醇量16倍,乙醇浓度80％,渗漉时间48h为最佳。结论采用乙醇渗漉工艺提取肾纤康颗粒提取物中丹参酮ⅡA的收率较高且稳定。     

乙醇对蟾蜍神经—肌接头传递的影响

目的 研究乙醇对神经肌肉接头（NMJ）兴奋传递的影响及可能机制。方法 用微电极细胞内记录的方法,在20只成年蟾蜍的坐骨神经－缝芹肌标本上研究了乙醇对终板电位（EPP）和微小终板电位（MEPP）的影响。结果 乙醇可引起EPP振幅改变,影响NMJ的兴奋传递,而且其影响具有明显的量效依赖关系,适当浓度的乙醇能明显地增加EPP振幅,促进MMJ的兴奋传递。乙醇还可使MEPP的增加,但对MEPP的振幅无影响。结论 初步确定乙醇促进NMJ兴奋传递的部位是在突触前,其机制是使 突触前释放的递质的量子数增加。     

Release of mitochondrial rather than cytosolic enzymes during liver regeneration in ethanol-intoxicated rats

BACKGROUND: Partial hepatectomy (PH) promoted rapid increase in serum of hepatic enzyme activities localized in mitochondria preferentially to increase enzyme activities from cytosol; low doses of ethanol (EtOH) administered to PH rats expedited return to normality of these elevated serum enzyme activities. The fate of released mitochondrial enzymes from liver was investigated in this study to advance knowledge of the role of mitochondria during priming phase of liver regeneration. METHODS: Catalytic activity of mitochondrial and cytosolic proteins was measured in remnant liver after PH and in elutes of perfused remnant livers from control and ethanol-intoxicated rats. RESULTS: During the first 24 h of liver regeneration (LR), mitochondrial enzymes--glutamate dehydrogenase, aspartate amino transferase, and malate dehydrogenase--diminished 33-58% in mitochondria, increased 17% in cytosol, and for two enzymes rose 68-86% in perfusates. Cytosolic lactate dehydrogenase decreased transiently in cytosol (24%) and increased only 13% in perfusates. Activity of cytochrome oxidase [corrected] (mitochondrial membrane-attached enzymes) was not modified. Ethanol intoxication after PH produced earlier and slightly higher extrusion of matrix mitochondrial enzyme activities. CONCLUSIONS: Selective increase of mitochondrial membrane permeability appeared as an important event during priming phase of LR after PH, thus sustaining preferential release of mitochondrial proteins outside the organelle in comparison with limited redistribution of cytosolic and mitochondrial membrane proteins. High doses of EtOH delayed LR and re-enforced mobilization of proteins produced by PH probably by enhancing greater mitochondrial membrane permeability.     

乙醇对兔心室肌细胞L-型钙离子通道电流的影响

【目的】观察乙醇对兔心室肌细胞L-型钙离子通道电流（ICa,L）的影响。【方法】采用蛋白酶消化的成年兔单个心室肌细胞及膜片钳全细胞技术，记录不同浓度乙醇对ICa,L的作用。【结果】（1）乙醇抑制ICa,L峰值，24mmol／L和240mmol／L乙醇抑制率差异有统计学意义（P〈0．05）。（2）24、80、240mmol／L乙醇使ICa,L的电流一电压（I—V）曲线上移，在各测试电压下，电流均减小，但不影响曲线形状，用乙醇后最大激活电压仍在0mV左右。【结论】致毒浓度（24mmol／L）的乙醇对ICa,L具有明显抑制作用。可导致心肌产生负性肌力作用，动作电位时程缩短，诱发心律失常。     

海南绞股蓝乙醇提取物的降血糖作用

目的评价海南绞股蓝乙醇提取物对实验小鼠的降血糖效果。方法用四氧嘧啶诱发高血糖小鼠模型,观察提取物对高血糖小鼠的降血糖效果:然后考察提取物对葡萄糖引致的小鼠血搪升高及对正常小鼠血搪水平的影响。结果四氧嘧啶诱发的高血糖模型小鼠的血糖水平平均为(19.45±2.60)/mmol.L-1,海南绞股蓝乙醇提取物的3个剂量组均能显著降低此模型小鼠的血糖水平分别至(16.60±2.76)/mmol.L-1,(15.21±2.46)/mmol.L-1和(13.05±1.88)/mmol.L-1。海南绞股蓝乙醇提取物还能明显抑制葡萄糖引致的小鼠血糖的升高,但对正常小鼠血糖无明显影响。结论海南绞股蓝乙醇提取物具有明显的降血糖作用,但不影响正常小鼠的血糖水平。     

Effects of ranitidine on blood alcohol levels after ethanol ingestion. Comparison with other H2-receptor antagonists.

OBJECTIVE--To determine whether the H2-receptor antagonist, ranitidine, which is a potent inhibitor of gastric alcohol dehydrogenase activity in vitro, increases the bioavailability of orally administered ethanol (0.3 g/kg of body weight) and to compare the resulting blood alcohol concentrations with those of two other H2-antagonists, cimetidine and famotidine, the latter of which does not inhibit gastric alcohol dehydrogenase. DESIGN--For each of the H2-receptor antagonists, a different group of subjects was used. In each group, a paired design was adopted with each subject serving as his own control. SETTING--Hospital laboratory. SUBJECTS--Normal, healthy men aged 24 to 46 years. INTERVENTION--Eight men were treated for 1 week with ranitidine (300 mg/d), six with cimetidine (1000 mg/d), and six with famotidine (40 mg/d). MEASURES--Peak blood alcohol concentrations, areas under the blood alcohol curve, first-pass metabolism, and bioavailability of orally consumed ethanol. RESULTS--Relative to baseline, ranitidine increased the mean peak concentration and the area under the curve of blood alcohol concentrations by 34% (P less than .05) and 41% (P less than .01), respectively. First-pass metabolism of ethanol was decreased from 70 +/- 10 to 31 +/- 9 mg/kg of body weight, with a corresponding increase in ethanol bioavailability of 79.6% to 92.6%. By comparison, cimetidine had even a greater effect on blood alcohol levels, while famotidine had no significant effects. CONCLUSION--Patients treated with ranitidine or cimetidine should be warned of possible functional impairments after consumption of amounts of ethanol considered safe in the absence of such therapy.     

乙醇对蟾蜍神经-肌接头传递的影响

目的　研究乙醇对神经肌肉接头 (NMJ)兴奋传递的影响及可能机制。方法　用微电极细胞内记录的方法 ,在 2 0只成年蟾蜍的坐骨神经 -缝匠肌标本上研究乙醇对终板电位 (EPP)和微小终板电位 (MEPP)的影响。结果　乙醇可引起 EPP振幅改变 ,影响 NMJ的兴奋传递 ,而且其影响具有明显的量效依赖关系 ,适当浓度的乙醇能明显地增加 EPP振幅 ,促进 NMJ的兴奋传递。乙醇还可使 MEPP的频率增加 ,但对 MEPP的振幅无影响。结论　初步确定乙醇促进 NMJ兴奋传递的部位是在突触前 ,其机制是使突触前释放的递质的量子数增加