肝胃乙醇脱氢酶活性变化与酒精性肝病发生的关系

目的 探讨肝、胃乙醇脱氢酶（ADH）活性的变化在酒精性肝病（ALD）不同病理阶段中的作用。方法 Wistar大鼠39只随机分成两组：模型组24只,对照组15只,用乙醇直接灌胃的方法建立大鼠ALD模型;用酶组织细胞化学染色技术,观察ALD不同病理阶段肝、胃ADH活性变化,并用LUZEX－F灰度图像分析仪进行ADH半定量。结果 ALD不同病理阶段肝ADH活性进行性增加,胃ADH活性进行性下降,两者均与对照组比较差异有显著性（P＜0．05）。结论 肝、胃ADH活性变化可能在ALD发生发展中起重要作用。     

乙醇首过代谢发生部位的实验性研究

目的探讨乙醇首过代谢发生的部位,从而为酒精性疾病的治疗提供新的思路。方法Wistar大鼠40只随机分成两组:模型组24只,对照组16只,建立大鼠酒精模型。用酶组织细胞化学染色技术,在光镜下观察肝胃乙醇脱氢酶(alcoholdehydrogenaseADH)活性变化,并用灰度图像分析仪进行半定量。结果长期摄入乙醇后肝ADH活性进行性增加,胃ADH活性进行性下降,两者对照差异显著(P<0.05)。结论结合文献得出乙醇的首过代谢发生在胃;诱导胃ADH的活性,可降低乙醇对机体的毒性作用。     

胃舒散对乙醇诱导大鼠急性胃损伤的保护作用

目的研究胃舒散对乙醇所致急性胃黏膜损伤（AGML）的保护作用。方法采用乙醇灌胃诱导大鼠AGML模型。采用光镜、扫描电镜和透射观察不同剂量胃舒散（3．0、1．5、0．75g／kg）对黏膜组织形态学的保护作用，并同时检测胃黏膜局部血流量（GMBF）、跨膜电位（PD）、胃组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量和血浆NO水平，等容积的生理盐水和丽珠得乐（1．0g／kg）分别作为正常对照和治疗对照组。结果胃舒散组胃黏膜损伤指数及组织学评分均较模型对照组显著降低（P〈0．05，P〈0．01）；GMBF及PD较模型对照组显著增高（P〈0．0l，P〈0．05）；胃舒散可明显提高胃组织SOD活性（P〈0．05）及血浆NO水平（P〈0．叭）。结论胃舒散对乙醇所致AGML有明显的保护作用，其作用机制可能与增加胃黏膜血流及抗氧化作用有关。     

中药护肝灵对实验大鼠乙醇分解酶的影响

目的：探讨中药护肝灵对乙醇代谢相关酶的影响．方法：以乙醇灌胃法复制大鼠模型,分别以易善复及高、低剂量护肝灵处理,双波长法检测血中乙醇浓度,按试剂盒说明书检查肝匀浆中CAT含量,活性分光光度法检测肝匀浆ADH含量,荧光实时定量RT-PCR观察ADH和CYP450ⅡE1的mRNA表达．结果：与正常对照组相比,模型组血清乙醇含量显著升高(545．7±l08．85mg/L vs -51．4±2．83mg/L,P＜0．05),ADH和CAT含量显著降低(667±272nkat/L vs 1884±650nkat/L,P＜0．05：112±29nkat vs 255±43nkat,P＜0．05)．与模型组相比,中药护肝灵可以降低口服乙醇大鼠血中乙醇含量(低剂量：248．5±96．63mg/L；高剂量：-0．1±33．94mg/L；均P＜0．01),提高肝组织ADH(低剂量：1184±422nkat/L：高剂量：1550±458nkat/L；均P＜0．05)和CAT(低剂量：202±31nkat/L；高剂量：167±34nkat/L；均P＜0．05)含量,造模后肝组织CYP450ⅡE1 mRNA显著下降(10±2 vs 15±2,P＜0．01),护肝灵可使肝组织CYP450ⅡE1 mRNA表达进一步下降(高剂量：8±2,P＜0．05)．造模及药物处理后,ADH mRNA均无显著变化(P＞0．05)．结论：中药护肝灵可激活乙醇代谢相关酶,进而促进乙醇在体内的代谢．     

单味鲜葛花汁对急性酒精中毒大鼠乙醇代谢的影响

目的:观察鲜葛花汁对急性酒精中毒大鼠体内乙醇代谢的影响,探讨鲜葛花汁预防醉酒作用的机制。方法:90只大鼠随机分为正常组、模型组、鲜葛花汁大、中、小剂量组和海王金樽组,除正常组外,其余各组大鼠均用白酒灌胃法造模。采用乙醇干片试剂法分别测定末次灌胃后1、2、3、5小时大鼠血中乙醇浓度;用比色法测定大鼠肝、胃组织乙醇脱氢酶(ADH)活性的变化;分别用黄嘌呤氧化酶法、TBA法、比色法检测大鼠肝组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的含量。结果:鲜葛花汁各组大鼠血中乙醇浓度低于模型组,差异有显著性意义(P<0.01);鲜葛花汁各组大鼠肝、胃组织ADH活性高于模型组(P<0.05),鲜葛花汁可显著提高大鼠肝组织SOD、GSH-Px水平,降低MDA水平,与模型组相比差异有显著性意义(P<0.01)。结论:鲜葛花汁通过提高ADH活性,加强乙醇在胃肠道的首过效应,降低血中的乙醇浓度,激活微粒体乙醇氧化系统(MEOS),加速乙醇及其代谢产物的消除速率,达到解酒的目的。     

葛根素对慢性乙醇中毒小鼠胃窦黏膜胃泌素、生长抑素表达的影响

目的探讨慢性乙醇中毒小鼠胃窦黏膜胃泌素（Gas）和生长抑素（SS）表达的变化及葛根素预处理的影响。方法健康雄性BALB／C小鼠24只，随机分为生理盐水对照组（SC组）、慢性乙醇中毒组（CAI组）和葛根素预处理组（PUE组）各8只，应用免疫组织化学SABC法和图像分析技术对Gas、SS在各组小鼠胃窦黏膜中的表达进行检测。结果PUE组小鼠胃窦内Gas阳性细胞数量较CAI组减少（P〈0．05），三组阳性细胞的平均灰度值无统计学差异。与CAI组比较，PUE组和SC组胃窦内SS阳性细胞数量较多，免疫染色增强，平均灰度值下降（P均〈0．05）。结论乙醇影响小鼠胃窦内Gas、SS的表达，葛根素可调控Gas、SS的表达，对乙醇性胃黏膜损伤有保护作用。     

抗脂肪肝冲剂对大鼠乙醇性肝损伤防治的实验研究

目的：探讨抗脂肪肝冲剂对乙醇性肝损伤大鼠脂质代谢的影响,寻找针对乙醇所致脂肪肝的有效药物,方法：采用乙醇慢性肝损伤模型,观察大鼠肝组织总胆固醇（TC）,及甘油三酯（TG）的含量,结果：抗脂肪肝冲剂降低乙醇性肝损伤大鼠肝组织TC,TG的含量,与模型组比较P＜0．05（小剂量组）,P＜0．01（中,大剂量组）,病理检查,抗脂肪冲剂各剂量组与模型组比较P＜0．01,结论：抗脂肪肝冲剂能够降低乙醇性肝损伤大鼠肝组织TG,TC的含量,具有防治乙醇性脂肪肝的作用。     

乙醇灌胃对大鼠精浆生化指标及精子动态参数的影响

目的：观察不同剂量乙醇灌胃对大鼠精浆生化及精子动态参数的影响。方法将40只健康雄性成年SD大鼠随机分为4组,其中对照组给予5 g/（kg· d）蒸馏水灌胃,低、中、高剂量乙醇组分别给予0．5、2．5、5 g/（kg＆#183; d）无水乙醇灌胃,连续20周。测定各组大鼠精浆生化（α-葡萄糖苷酶、酸性磷酸酶、精浆果糖、精浆锌）及精子动态参数（精子密度、平均速率、直线运动速率、曲线运动速率、精子头侧摆幅度、鞭打频率、前向性、直线性）的变化情况。结果与对照组相比,各剂量乙醇组的精浆生化含量均降低（P＜0．05或＜0．01）,精子动态参数均明显减弱（P＜0．05或＜0．01）。与低剂量组相比,中剂量组精浆生化除α-糖苷酶外含量均降低,高剂量组精浆生化含量均降低（ P＜0．05或＜0．01）;中、高剂量组精子动态参数均明显减弱（P＜0．01）。结论乙醇灌胃可导致雄性大鼠精浆生化指标与精子动态参数出现不同程度的异常,中高剂量比低剂量影响更大。     

酒精性肝病不同阶段大鼠胃乙醇脱氢酶活性变化研究

目的 探讨酒精性肝病（Ａｌｃｏｈｏｌｉｃ ｌｉｖｅｒ ｄｉｓｅａｓｅ，ＡＬＤ）不同病理阶段胃乙醇脱氢酶（Ａｌｃｏｈｏｌ ｄｅｈｙｄｒｏｇｅｎａｓｅ，ＡＤＨ）活性变化。方法 用酶组织细胞化学梁色技术，在光镜下观察酒精性肝病不同阶段胃ＡＤＨ活性变化，并用ＬＵＺＥＸ－Ｆ灰度图像分析仪半定量。结果 ＡＬＤ不同阶段胃ＡＤＨ活性进行性下降，差异有显著性（Ｐ〈０．０５）。结论 提示酒精性肝病不同阶段胃ＡＤＨ活性     

清肝活血方对酒精性肝病大鼠ADH及CYPⅡE1的影响

目的：观察清肝活血方对酒精性肝病大鼠乙醇代谢关键酶基因表达的影响。方法：用乙醇、玉米油、吡唑等制备酒精性肝病大鼠模型。RR－PCR法检测大鼠肝组织ADH及P450ⅡE1mRNA表达。结果：酒精性肝病大鼠模型表现为肝功能异常，以AST变化为显著；模型组AH活性及其mRNA与P450ⅡE1mRNA表达下降；高剂量清肝活血方组大鼠ADH活性及ADH与P450ⅡE1mRNA的表达显著提高。结论：清肝活血方能显著提高模型组大鼠ADH活性及ADH与YPⅡE1mRNA的表达，促进肝脏的解毒功能。     

Zinc Administration Improves Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Alcohol-Fed Rats

The effects of zinc on first-pass metabolism (FPM) of ethanol and gastric and hepatic alcohol dehydrogenase (ADH) activities have been investigated in two groups of male Wistar rats fed a liquid ethanol diet with normal zinc content (7.6 mg/liter), or zinc supplemented (76 mg/liter), for 21 days, and in two pair-fed groups receiving the same diets without ethanol. Alcoholic rats with normal dietary zinc had lower FPM (1.64 ± 0.25 vs. 2.43 ± 0.20 mM ± hr, p < 0.05) and gastric ADH activity (184 ± 7 vs. 335 ± 41 μmol/min/mg protein, p < 0.01) than control rats. Zinc supplementation did not produce any change in FPM or in gastric ADH activity in control rats. By contrast, in alcoholic rats, the zinc supplement increased gastric ADH activity (247 ± 31 vs. 184 ± 7 μmol/min/mg protein, p < 0.05) and decreased the areas under the curve of blood ethanol concentrations after the intragastric administration of 0.25 g/kg of body weight of ethanol (0.78 ± 0.07 vs. 1.71 ± 0.24 mM ± hr, p < 0.05), thereby increasing the FPM. In conclusion, in alcohol-fed rats, the administration of zinc supplements restores gastric ADH activity and improves the FPM of ethanol. These effects may be one of the mechanisms in which zinc has a beneficial role in preventing the development of alcoholic hepatic lesions.     

Alcohol Dehydrogenase (ADH) Isoenzymes and Aldehyde Dehydrogenase (ALDH) Activity in the Sera of Patients with Gastric Cancer

BACKGROUND: Investigations have shown that alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are present in some cancer cells and can play role in carcinogenesis. In recent experiments we found elevated alcohol dehydrogenase class IV activity in gastric cancer cells. This suggests these changes may be reflected by enzyme activity in the serum. AIM: In this work we measured the activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in the sera of patients with gastric cancer matched on gender. METHODS: Serum samples were taken for routine biochemical investigation from 55 patients with gastric cancer, before treatment, and from 55 control subjects. Total ADH activity was measured photometrically and ALDH activity by a fluorimetric method. For measurement of the activity of class I isoenzymes we used a fluorimetric method, with class-specific fluorogenic substrates. The activity of class III and IV alcohol dehydrogenase was measured photometrically. RESULTS: The activity of the class IV ADH isoenzyme was significantly higher in the sera of patients with gastric cancer. The median activity of this isoenzyme in the total cancer group was approximately 47% higher (7.45 mU/l) than the control level (5.08 mU/l). For this reason total ADH activity was also significantly increased. The activities of other tested ADH isoenzymes and ALDH were unchanged. CONCLUSION: Changes in the activity of, especially, class IV ADH in the sera of patients with gastric cancer seems to be caused by release of the isoenzyme from cancer cells.     

Alcohol Dehydrogenase (ADH) Isoenzyme Activity in the Sera of Patients with <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection

Human gastric mucosa contains three classes of alcohol dehydrogenase (ADH) isoenzymes: I, III, and IV. Various factors have been found to influence gastric ADH activity. One of them is Helicobacter pylori infection, which is associated with gastric mucosal injury and leads to a decrease in gastric ADH activity. The aim of the study was to assess the effect of H. pylori infection on the serum activity of ADH isoenzymes. Serum samples were taken from 35 patients with H. pylori infection and from 35 healthy subjects. For measurement of class I isoenzyme activity we employed the fluorometric method, with class-specific fluorogenic substrate (4-methoxy-1-naphthaldehyde). The activities of class III and IV ADH isoenzymes were measured by the photometric method with formaldehyde and with m-nitrobenzaldehyde as substrate, respectively. Total activity of ADH was measured by a photometric method with p-nitrosodimethylaniline. The total activities of ADH and class IV isoenzyme were significantly higher in sera of patients with H. pylori infection compared to healthy subjects. The serum activity of other tested isoenzymes of ADH did not differ significantly between infected and noninfected groups. We conclude that H. pylori infection of gastric mucosa is reflected in the serum by a significant increase in class IV and total ADH activity.     

Atypical Liver Alcohol Dehydrogenase in the Spanish Population: Its Relation with the Development of Alcoholic Liver Disease

The presence of atypical liver alcohol dehydrogenase (ADH) was determined in samples of liver tissue from 222 alcoholic and nonalcoholic subjects to determine its prevalence in the Spanish population, and to evaluate the possible relationship between the presence of this isoenzyme and the development of alcoholism and alcoholic liver disease. Alcoholic patients were classified into the following groups: control subjects, with normal liver pathology (group 1), patients with noncirrhotic liver disease (group 2), and patients with cirrhosis of the liver (group 3). Nonalcoholic subjects were also divided, following the same criteria, into groups 4, 5, and 6, respectively.
The prevalence of atypical ADH in the population analyzed was 16.2%. Atypical ADH was present in 14.9% of alcoholics and in 17.4% of nonalcoholics ( P = ns ). There were no significant differences when the prevalence of atypical ADH of alcoholic and nonalcoholic patients with similar degrees of liver pathology was compared (group 1 vs. 4, group 2 vs. 5, and group 3 vs. 6). The prevalence of atypical ADH was also similar in cirrhotic patients with respect to those of noncirrhotic liver disease and control patients, either in alcoholic or nonalcoholic groups.
Our findings indicate that the prevalence of atypical ADH in the Spanish population is similar to that reported for other Caucasian groups. Moreover, the presence of atypical ADH does not play a role in the development of alcoholism nor in the development of alcoholic liver disease in the population analyzed.     

西米替丁及法莫替丁对胃乙醇脱氢酶活性的影响

应用紫外分光光度法体外观察不同浓度的西米替丁及法莫替丁对胃乙醇脱氢酶活性的影响。结果表明：当西米替丁浓度为０．０１ｍｍｏｌ／Ｌ时，ＡＤＨ活性明显下降，抑制率为４４．９％，药物浓度越高，抑制作用越强。     

Alcohol Dehydrogenase Activities in the Human Gastric Mucosa: Effects of Helicobacter pylori Infection, Sex, Age, and the Part of the Stomach

Background: Human gastric mucosa contains three alcohol dehydrogenase (ADH) isozymes (classes I, III, and IV). Various factors such as Helicobacter pylori infection, sex, age, and the part of the stomach involved have been suggested to affect alcohol dehydrogenase activities, although these views are controversial. In this study, these unsettled issues were reexamined.
Methods: Activities of class I and IV ADHs were evaluated in the cytosolic fraction of human gastric mucosa samples by reduction of their preferred substrates, namely acetaldehyde and m-nitrobenzaldehyde, and activities of class III were evaluated by oxidation of its preferred substrate, formaldehyde. Then, effects of Helicobacter pylori infection, sex, age, and the part of the stomach involved were examined.
Results: Class I, III, and IV ADH activities were 17.5 ± 8.4, 4.2 ± 2.5, and 8.9 ± 3.9 nmol of nicotinamide adenine dinucleotide oxidation per minute per milligram of protein, respectively, for the entire population. Helicobacter pylori infection significantly reduced class I and IV ADH activities but did not affect activity of class III. In the samples without Helicobacter pylori infection and severe gastritis, sex did not affect class I, III, or IV ADH activities. In the same series, class IV ADH activity significantly decreased with age ( p = 0.006), whereas no correlation was found between age and ADH activity of class I and III ADHs. The level of class IV ADH activity was significantly higher in the upper body than in the lower regions, whereas no such heterogeneity was observed in class I and III ADH.
Conclusions: Various factors affect human gastric ADH activities, such that careful interpretation of their significance is necessary.     

The Activity of Class I,III, and IV of Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in Gastric Cancer

The metabolism of cancer is in many way different than in healthy cells. Increased metabolism of several carcinogenic substances may take place in cancer cells. The one of them was ethanol, that is oxidized by alcohol dehydrogenase (ADH) to high concentration of acetaldehyde, a toxic and carcinogenic compound. The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase (ALDH). The aim of this study was to compare the capacity for ethanol metabolism measured by ADH isoenzymes and ALDH activity between gastric cancer and normal gastric mucosa. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the measurement of the activity of class I isoenzymes, we used fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate. The samples were taken surgically during routine operations of gastric carcinomas from 55 patients. The activities of total ADH, and the most important in gastric mucosa, class IV ADH were significantly higher in cancer cells than in healthy tissues. The other tested classes of ADH and ALDH showed a tendency toward higher activity in cancer than in healthy mucosa. The activities of all tested enzymes and isoenzymes were not significantly higher in men than in women in wither gastric cancer tissues or normal mucosa. The increased ADH IV activity may be 1 of the factors intensifying carcinogenesis by the increased ability to acetaldehyde formation from ethanol.     

Alcohol dehydrogenase polymorphisms influence alcohol-elimination rates in a male Jewish population

BACKGROUND: Genetic variation in the alcohol dehydrogenase (ADH) enzyme is associated with an aversion to alcohol and a lower risk of alcoholism among Asians. There is growing evidence of a functional role of the ADH2*2 allele in alcohol-drinking patterns among Jews, who have traditionally exhibited low rates of alcoholism and alcohol-related problems. The mechanism by which this allelic effect is mediated is not yet clearly understood. This study examined the effect of ADH2*2 on alcohol-elimination rates (AER) under experimental conditions. METHODS: Young adult male Jews (N = 109) received an intravenous alcohol infusion; metabolism was measured by using standard breath alcohol concentration tests. A clamping technique was used to achieve and maintain a target breath alcohol concentration of 50 mg/100 ml for a defined time period. The AER at steady state was calculated. The alcohol disappearance rate was also calculated from the descending limb slope. Polymerase chain reaction was used for allelic determination of the ADH2 and ADH3 loci. RESULTS: The mean AER among ADH2*2 carriers was significantly higher (8.09 +/- 1.4 g/hr) than among ADH2*1 homozygotes (7.14 +/- 1.5 g/hr; p = 0.003). Significance was retained on adjustment for potential confounding covariates. The ADH2 allele explains 8.5% of the AER variance in this population. Little AER difference was observed across ADH3 genotype groups. The slope of the descending limb increased with increasing copies of the ADH2*2 allele. CONCLUSIONS: The rate of alcohol elimination is significantly associated with the ADH2 genotype of Jewish males. Evidence for variation in alcohol metabolism across ADH genotypic groups provides support for the role of physiologic protective factors in alcohol drinking and suggests that reduced drinking among Jews may be genetically as well as environmentally determined. We believe that application of the novel "Indiana clamp" enhances AER measurement accuracy, allowing for detection of hitherto undetectable differences.