乙醇及其代谢产物乙醛对胎鼠大脑星形胶质细胞增殖的影响

为探讨孕期饮酒致胎儿神经系统发育异常和发育迟缓机制,本研究在体外利用３Ｈ－ＴｄＲ参入胎鼠大脑星形胶质细胞以研究乙醇及其代谢产物乙醛对其增殖的影响。结果表明乙醇、乙醛均可明显抑制星形胶质细胞增殖,乙醛的抑制作用强度明显高于乙醇。结果表明,乙醇、乙醛对星形胶质细胞生长有明显抑制作用。酒精引起的神经系统发育异常很可能是乙醇及其代谢产物对星形胶质细胞增殖抑制所致。     

Catecholamines in hyperpnoea‐induced airway constriction of guinea pigs

1 We found previously that propranolol augments hyperpnoea‐induced bronchoconstriction (HIB). This study was performed to investigate the underlying mechanism of this aug‐ menting action of propranolol. 2 In the first series, 45 young Hartley guinea‐pigs were divided into five groups: control; propranolol; adrenalectomy; metoprolol and reserpine. Each animal underwent three periods: baseline, hyperpnoea, and recovery. For each animal 1 ml of arterial blood was sampled during the baseline and recovery periods. 3 Treatments of propranolol, metoprolol, and reserpine caused significant decreases in both dynamic respiratory compliance (C_rs) and forced expiratory volume in 0.1 s (FEV_0.1) during the baseline period. Hyperpnoea caused slight but not significant decreases in C_rs, FEV_0.1, and maximal expiratory flow at 50% total lung capacity (TLC) (V˙_max50) during the recovery period in the control group. Propranolol, but not other treatments, significantly augmented these decreases (indicating HIB). Plasma noradrenaline and adrenaline levels in the reserpine group were not detectable. The above treatments or hyperpnoea did not induce any significant effect on the plasma noradrenaline level. Plasma adrenaline level of the control group was higher than that of either adrenalectomy or reserpine group during the baseline and the recovery periods. 4 In the second series, we avoided repeated blood samplings. Forty‐eight animals were evenly divided into two groups: control and propranolol. Each group was again evenly divided into three subgroups: baseline; hyperpnoea, and recovery. Five minutes into the recovery period, we demonstrated HIB in the control group. In terms of V˙_max50, this HIB was significantly augmented by propranolol. Plasma noradrenaline and adrenaline levels, however, were not significantly altered by either hyperpnoea or propranolol. 5 Taken together, these data suggest that propranolol‐augmented HIB has no direct relationship with decreased catecholamine activity.     

基于基因毒性和对单抗聚集影响的聚山梨酯中醛限度的控制

通过建立HPLC柱前衍生化法对不同厂家的聚山梨酯80和聚山梨酯20中甲醛、乙醛进行检测分析,并在不同条件下监测甲醛和乙醛对阿达木单抗聚集的影响,分别从基因毒性杂质控制和对单抗制剂稳定性影响两方面综合考量,初步得出二者的控制限度.HPLC柱前衍生化法采用2,4-二硝基苯肼(2,4-DNPH)作为衍生化试剂,以乙腈和水为流...     

咖啡因对乙醛诱导的HSC-T6中TGF-β1,CTGF信号转导通路的影响

目的探讨咖啡因(caffeine)对乙醛诱导的大鼠肝星状细胞系(Hepatic Stellate Cell-T6,HSC-T6)中转化生长因子-β1(Trans-forming Growth Factor-β1,TGF-β1),结缔组织生长因子(Connective Tissue Growth Factor,CTGF)信号转导通路的影响。方法实验设正常组(常规培养),模型组及腺苷受体(Adenosine Receptor,AR)调节剂干预组。分别给予caffeine(4 mmol.L-1)[1-2],腺苷A2A受体拮抗剂ZM241385(1μmol.L-1)[3],腺苷A2A受体激动剂CGS21680(1μmol.L-1)[3],caffeine+CGS21680,ZM241385+CGS21680与HSC-T6共同培养,1 h后加入终浓度200μmol.L-1的乙醛刺激(每12 h补充1次),继续培养48 h。采用免疫细胞化学法检测HSC-T6中α-平滑肌肌动蛋白(α-SMA)的表达,RT-PCR法检测TGF-β1和CTGF mRNA水平,Western blot方法检测各组HSC-T6中CTGF蛋白表达。结果与模型组比较,caffeine及ZM241385均显著降低HSC-T6中α-SMA,TGF-β1和CTGF的表达,而caffeine及ZM241385合用CGS21680上述作用有所逆转。结论 Caffeine能够显著降低乙醛诱导的HSC-T6活化,并且显著抑制HSC-T6中TGF-β1和CTGF的表达水平,其机制可能与拮抗腺苷A2A受体介导的信号通路有关。     

蒿鳖养阴软坚方给药大鼠体内乙醛含量的测定

目的 研究建立蒿鳖养阴软坚方给药大鼠血浆中乙醛浓度的HPLC测定方法.方法 色谱柱Hypersil C18(250 mm×4.6 mm,5μm);流动相为乙腈-水,梯度洗脱(起始浓度5%,10 min15%,20 min40%),流速1.0 mL/min;柱温:30℃,检测波长:210 nm,进样量:10μL.结果 乙...     

Biochemical and ultrastructural alterations in the rat ventral prostate due to repetitive alcohol drinking

Previous studies showed that cytosolic and microsomal fractions from rat ventral prostate are able to biotransform ethanol to acetaldehyde and 1-hydroxyethyl radicals via xanthine oxidase and a non P450 dependent pathway respectively. Sprague Dawley male rats were fed with a Lieber and De Carli diet containing ethanol for 28 days and compared against adequately pair-fed controls. Prostate microsomal fractions were found to exhibit CYP2E1-mediated hydroxylase activity significantly lower than in the liver and it was induced by repetitive ethanol drinking. Ethanol drinking led to an increased susceptibility of prostatic lipids to oxidation, as detected by t-butylhydroperoxide-promoted chemiluminiscence emission and increased levels of lipid hydroperoxides (xylenol orange method). Ultrastructural alterations in the epithelial cells were observed. They consisted of marked condensation of chromatin around the perinuclear membrane, moderate dilatation of the endoplasmic reticulum and an increased number of epithelial cells undergoing apoptosis. The prostatic alcohol dehydrogenase activity of the stock rats was 4.84 times lower than that in the liver and aldehyde dehydrogenase activity in their microsomal, cytosolic and mitochondrial fractions was either not detectable or significantly less intense than in the liver. A single dose of ethanol led to significant acetaldehyde accumulation in the prostate. The results suggest that acetaldehyde accumulation in prostate tissue might result from both acetaldehyde produced in situ but also because of its low aldehyde dehydrogenase activity and its poor ability to metabolize acetaldehyde arriving via the blood. Acetaldehyde, 1-hydroxyethyl radical and the oxidative stress produced may lead to epithelial cell injury.     

Piecing together the puzzle of acetaldehyde as a neuroactive agent

Mainly known for its more famous parent compound, ethanol, acetaldehyde was first studied in the 1940s, but then research interest in this compound waned. However, in the last two decades, research on acetaldehyde has seen a revitalized and uninterrupted interest. Acetaldehyde, per se, and as a product of ethanol metabolism, is responsible for many pharmacological effects which are not clearly distinguishable from those of its parent compound, ethanol. Consequently, the most recent advances in acetaldehyde's psychopharmacology have been inspired by the experimental approach to test the hypothesis that some of the effects of ethanol are mediated by acetaldehyde and, in this regard, the characterization of metabolic pathways for ethanol and the localization within discrete brain regions of these effects have revitalized the interest on the role of acetaldehyde in ethanol's central effects. Here we present and discuss a wealth of experimental evidence that converges to suggest that acetaldehyde is an intrinsically active compound, is metabolically generated in the brain and, finally, mediates many of the psychopharmacological properties of ethanol.     

夏枯草总三萜对乙醛刺激的肝星状细胞作用及部分机制

目的:探讨夏枯草总三萜(TTP)对乙醛刺激的大鼠肝星状细胞(HSC)-T6增殖、凋亡的影响及部分作用机制.方法:用不同浓度的TTP(10、30、100、300、1000 μg/mL)对乙醛刺激的HSC-T6进行处理,四甲基偶氮唑蓝(MTF)法检测细胞增殖;流式细胞仪检测细胞凋亡;RT-PCR法检测HSC-T6中平滑肌肌动蛋白(α-SMA)、Ⅰ型前胶原(Procollagen Ⅰ)、TGF-β信号转导通路下游中介分子Smad2、Smad3、Smad7 mRNA表达.结果:TTP可抑制乙醛刺激的大鼠HSC-T6增殖,诱导其凋亡,下调HSC-T6中α-SMA、ProcollagenⅠ、Smad2、Smad3的mRNA表达,上调Smad7的mRNA表达.结论:TTP对乙醛刺激的HSC-T6增殖具有抑制作用,并能够促进其凋亡,下调α-SMA、Procollagen Ⅰ表达量,其机制可能与TTP能抑制Smad2、Smad3表达,升高Smad7的表达,从而对TGF-β/Smad信号通路发挥调控作用有关.     

抗乙醛蛋白加合物抗体在不同人群血清中的检测及临床意义

研究抗加合蛋白抗体滴度在不同人群血清中的变化及其临床意义。用牛血清白蛋白制备醛化抗原,然后用ELISA方法检测抗加合蛋白抗体滴度。结果抗加合物IgG、IgM、IgA抗体滴度在酒精性肝病者血清中明显高于无肝损伤的酗酒者、非酒精性肝病者及健康对照者;在酒精性肝病组,抗加合物IgG、IgM、IgA抗体滴度与血清AST、GGT呈明显的正相关(P分别<0．005),与白蛋白呈显著的负相关(P均<0．005);抗加合物IgG、IgM抗体滴度与血清LN、PCⅢ、CⅣ呈明显的正相关(P均<0．05),IgA抗体滴度与血清PCⅢ、CⅣ呈显著的正相关,P分别< 0．05和0．01。上述结果提示在酒精性肝病患者血清中存在抗加合物IgG、IgM、IgA的免疫反应,并且这种免疫反应与酒精性肝损伤有关。     

Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice

Aim:

To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice.

Methods:

Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1–3, respectively, and 18% in week 4–7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles.

Results:

Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles.

Conclusion:

Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.