CYP2E1在1,2-二氯乙烷致肝氧化损伤中的作用

分别将昆明种小鼠分成对照组、1,2-DCE染毒组和二烯丙基硫化物(DAS)干预组,检测肝组织中CYP2E1活性和蛋白表达、MDA和GSH含量及SOD活性。与对照组相比,1,2-DCE染毒组肝组织中CYP2E1活性和蛋白表达及MDA含量显著升高,GSH含量及SOD活性显著降低。与单纯染毒组相比,DAS干预组肝组织中CYP2E1活性和蛋白表达及MDA含量显著降低,GSH含量和SOD活性显著升高。说明1,2-DCE可诱导CYP2E1表达,导致肝组织出现氧化损伤。     

CYP2E1在1,2-二氯乙烷致脑氧化损伤中的作用

分别将昆明种小鼠随机分为对照组、单纯染毒组及低、中和高剂量二烯丙基硫化物(DAS)干预组。检测脑组织中CYP2E1蛋白和mRNA表达、MDA和GSH含量及SOD活性。单纯染毒组与对照组相比,小鼠脑组织中CYP2E1蛋白和mRNA表达及MDA含量显著升高,而GSH含量显著下降;DAS各干预组与单纯染毒组相比,CYP2E1蛋白和mRNA表达及MDA含量显著下降,GSH含量显著升高。提示1,2-DCE可诱导CYP2E1表达,导致脑组织氧化损伤。     

1例重度1,2-二氯乙烷中毒临床分析

报道1例亚急性重度1,2-二氯乙烷中毒患者的临床表现、救治经过及体会。     

1,2-二氯乙烷中毒性脑病1例报告

报告1例1,2-二氯乙烷（1,2-dichloroethane,1,2-DCE）中毒性脑病患者的临床诊治过程。患者中毒后以中枢神经受损表现为主,影像学检查提示双侧大脑半球脑白质少许缺血变性灶,明确诊断后给予糖皮质激素减轻脑水肿、营养神经等对症支持治疗,患者最终临床痊愈。提示1,2-二氯乙烷中毒性脑病早期明确诊断后,及时给予糖皮质激素等综合治疗,有助于改善患者的预后。     

维生素Ｅ对1，2-二氯乙烷中毒性脑水肿保护作用的研究

目的探讨维生素E (vitamin E,Vit E)对1,2-二氯乙烷(1,2-dichloroethane,1,2-DCE)中毒性脑水肿的保护作用。方法将雌性昆明种小鼠随机分为空白对照组、Vit E对照组、1,2-DCE单纯染毒组及Vit E低、中和高剂量干预组。连续给予药物灌胃4 d后,采取静式吸入方式染毒3. 5 h/d,持续3 d。结果与空白对照组相比,单纯染毒组小鼠脑组织呈现明显脑水肿病理改变,脑含水量、脑组织中丙二醛(malondialdehyde,MDA)含量及细胞色素P450 2E1 (cytochrome P450 2E1,CYP2E1)蛋白和mRNA表达水平显著升高,脑组织中还原型谷胱甘肽(glutathione,GSH)含量、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase assay kit,CAT)活性、Occludin蛋白和mRNA及Claudin 5蛋白表达水平显著降低。与单纯染毒组相比,各干预组小鼠的脑含水量、脑组织MDA含量、CYP2E1蛋白和mRNA表达水平显著降低,GSH含量、Occludin蛋白及mRNA水平显著升高;中和高剂量干预组的小鼠脑组织中SOD和CAT活性及Claudin 5蛋白表达水平亦显著升高(P0. 05)。结论单纯1,2-DCE染毒可引起小鼠脑水肿,诱导脑组织中CYP2E1的表达,诱发脑组织氧化损伤,破坏紧密连接蛋白,并抑制Occludin和Claudin 5的表达;而Vit E干预可显著抑制CYP2E1的表达,缓解CYP2E1介导的氧化损伤,有效预防1,2-DCE引起的中毒性脑水肿。     

亚急性重度1,2-二氯乙烷中毒致死2例报告

对2例1,2-二氯乙烷中毒死亡病例的临床资料及现场调查结果作一简要报道。     

1起急性1,2-二氯乙烷中毒事故调查

目的报告1起由于使用1,2-二氯乙烷清洗工作台面引起的急性中毒事故。方法调查生产工艺及事故经过、分析事故原因。结果现场调查发现此次事故为作业时没有采取任何职业病防护措施而引起的,经治疗9名患者全部治愈。结论从源头消除职业病危害是关键。     

急性1,2-二氯乙烷中毒继发吸入性肺炎1例

报道1例急性1,2-二氯乙烷中毒继发吸入性肺炎患者的救治经过。该患者中毒后出现意识丧失,继发吸入性肺炎、癫痫、肝肾功能障碍,经积极综合治疗后基本痊愈。提示早期诊治急性1,2-二氯乙烷中毒合并严重并发症,患者预后良好。     

硫辛酸治疗1,2-二氯乙烷中毒性脑病临床观察

目的 探讨硫辛酸治疗1,2-二氯乙烷中毒性脑病的疗效.方法 23例患者随机分为硫辛酸治疗组及对照组,对照组给予甘露醇、皮质激素和B族维生素、吡拉西坦等治疗,治疗组在对照组治疗的基础上,添加硫辛酸治疗,疗程4周.2组患者治疗前后分别行Glasgow昏迷量表、改良Rankin量表及Kokmen智能状态量表评价,以评定患者病情严重程度及疗效.结果 治疗组改良Rankin量表及Kokmen智能量表评分优于对照组,2组比较,差异均有统计学意义(P＜0.05).结论 硫辛酸可促进1,2-二氯乙烷中毒性脑病患者神经功能恢复,改善认知能力及生活质量.     

一起1,2-二氯乙烷中毒事故调查

目的了解中毒事故发生的原因,为职业病诊断提供依据。方法采用现场职业卫生学调查和职业病危害因素的检测方法进行识别和分析。结果两患者工作岗位工作场所空气中1,2-二氯乙烷C-TWA16.0mg/m3、C-STEL53.1mg/m3,分别超过职业卫生标准2.29和3.54倍。结论两患者诊断为职业性急性1,2-二氯乙烷轻度中毒。为防止中毒事故的再次发生,公司应立即采取整改措施。     

亚急性1,2-二氯乙烷染毒致小鼠肝组织氧化损伤的研究

本研究的目的是探讨亚急性1,2-二氯乙烷(1,2-DCE)中毒致肝脏氧化损伤情况,为阐明1,2-DCE中毒性肝损伤的机制提供参考依据。将昆明种小鼠随机分成对照组和不同剂量1,2-DCE染毒组(0.35、0.7、1.2 mg/L),采用静式吸入方式染毒1周;然后,取血和肝组织,分别检测血中总胆红素(TB)和谷胱甘肽(GSH)含量,肝组织中丙二醛(MDA)、GSH含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性。结果中、高剂量染毒组小鼠的血浆中TB含量显著高于对照组小鼠;而中、高剂量染毒组小鼠的肝组织中GSH-Px活性和GSH含量及高剂量组的SOD活性显著低于对照组,高剂量染毒组小鼠的肝组织中MDA含量显著高于对照组。提示亚急性1,2-DCE中毒可引起肝组织的氧化性损伤。     

Impairment of lipoglycoprotein metabolism in rat liver cells induced by 1,2-dichloroethane.

BACKGROUND--1,2-Dichloroethane (DCE) is a volatile liquid readily absorbed through dermal, digestive, or inhalatory routes. After inhalation or oral administration to rats, death occurs within a narrow range of concentrations (six hour LC50 = 5100 mg/m3). Exposure to single high doses of DCE resulted in adverse effects on the central nervous system, liver, kidneys, adrenals, and lungs. The liver showed fatty changes and hepatocellular necrosis with haemorrhage. These injuries are probably related to changes in several cell functions and constituents. Therefore, it was decided to investigate whether DCE was capable of impairing the secretion of hepatocellular lipoglycoproteins acting both at the level of the Golgi apparatus and endoplasmic reticulum. METHODS--Isolated hepatocytes of Wistar rats were prelabelled with two precursors of lipoglycoproteins 3H-Na-palmitate and 14C-glucosamine, and then exposed to concentrations of DCE from mean (SD) 4.4 (0.03) to 6.5 (0.02) mM for different durations ranging from five to 60 minutes. To measure lipid and sugar bound radioactivity, a preliminary separation of cell homogenate, cytosol, total microsomes, Golgi apparatus, and lipoglycoproteins secreted into cell suspension medium was carried out. RESULTS--After five minutes of exposure, DCE did not induce obvious changes in cell viability or lactic dehydrogenase leakage, but a significant (p < 0.01) depletion of reduced glutathione content was seen (40.10 (4.3) nM/10(6) cells). Furthermore, the cells poisoned by DCE started to show noticeable accumulation of 3H-Na-palmitate in the Golgi apparatus after five minutes (5103 (223) dpm/10(6) cells) and in the microsomes after 15 minutes (85,470 (7190) dpm/10(6) cells). There was a simultaneous significant increase in 14C-glucosamine content in the Golgi apparatus (690 (55) dpm/10(6) cells) and the microsomes (15,975 (2035) dpm/10(6) cells). The specific radioactivity of lipid and sugar moieties incorporated in secreted lipoglycoproteins was already significantly reduced after only five minutes of exposure (480 (57) dpm/10(6) cells for lipids, and 315 (45) dpm/10(6) cells for sugars). CONCLUSIONS--Overall, DCE, like other haloalkanes, produces a block of secretion of hepatocellular lipoglycoproteins as early as five minutes after poisoning. The simultaneous percentage increases into Golgi apparatus and microsomes of lipid and sugar bound radioactivity suggest that lipid retention at the sites of processing of lipoglycoproteins would probably play an important part in the early stages of cellular accumulation of fat after exposure to DCE.     

N-甲基-D-天冬氨酸Ⅰ型受体在1,2-二氯乙烷急性中毒性脑病中的表达

目的研究N-甲基-D-天冬氨酸Ⅰ型受体(NMDAR1)在1,2-二氯乙烷(1,2-DCE)急性中毒性脑病发病中的作用。方法SD大鼠42只,随机分为1个对照组、3个染毒组和3个染毒后时间观察组,每组6只。染毒组和时间观察组连续静式吸入1,2-DCE 12 h,对照组不接触1,2-DCE和其他化学物。染毒组接触剂量分别为5.0、10.0、20.0 g/m~3,时间观察组接触剂量均为10.0 g/m~3,染毒结束后在干净无毒的环境中分别放置2、4、6 h；NMDAR1在大鼠脑组织中的表达采用免疫组织化学法检测。结果NMDAR1阳性神经元主要分布在大脑皮质和海马。阳性细胞百分比结果：(1)10.0、20.0g/m~3剂量组表达量高于对照组,差异有统计学意义(P＜0.05)。大脑皮质分别为(18.33±1.86)%、(64.17±2.86)%,对照组(1.83±0.75)%；海马分别为(15.5±1.87)%、(47.83±2.16)%,对照组(0.83±0.75)%；(2)时间观察组表达量：大脑皮质2、4、6 h组高于对照组和10.0 g/m~3剂量组,差异有统计学意义(P＜0.05)；表达量分别为(39.07±3.01)%、(70.17±2.93)%、(39.83±2.32)%。海马2、4、6 h组也高于对照组,表达量分别为(16.30±1.03)%、(19.80±1.17)%、(16.50±1.05)%,差异有统计学意义(P＜0.05)；但与10.0 g/m~3剂量组比较,仅4 h组有明显增加,差异有统计学意义(P＜0.05)。结论1,2-DCE急性中毒过程中,NMDAR1表达数量明显上调,兴奋性氨基酸可能通过大量NMDAR1的快速开放参与脑皮质细胞的急性肿胀过程,加重脑水肿的发生。     

Ethanol-induced oxidative DNA damage and CYP2E1 expression in liver tissue of Aldh2 knockout mice

Excessive alcohol consumption is associated with increased risks of many diseases including cancer. We evaluated oxidative DNA damage in Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. Olive tail moment, which was measured using a comet assay, was not increased by ethanol treatment in both Aldh2 +/+ and Aldh2 -/- mice. However, after controlling for the effect of ethanol exposure, the Aldh2 genotype was a significant determinant for Olive tail moments. Although the ethanol treatment significantly increased the hepatic 8-OHdG generation in only Aldh2 +/+ mice, the level of 8-OHdG was the highest in Aldh2 -/- ethanol treated mice. The increase in the level of 8-OHdG was associated with hepatic expression of cytochrome P450 2E1 (CYP2E1). The levels of Olive tail moment and the hepatic 8-OHdG in the Aldh2 -/- control group were significantly higher than those of the Aldh2 +/+ control group. The level of CYP2E1 in liver tissue showed a similar pattern to those of the oxidative DNA damage markers. This study shows that acute ethanol consumption increases oxidative DNA damage and that expression of CYP2E1 protein may play a pivotal role in the induction of oxidative DNA damage. The finding that oxidative DNA damage was more intense in Aldh2 -/- mice than in Aldh2 +/+ mice suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated liver disease, including cancer.     

1，2-二氯乙烷致中毒性脑病中神经细胞的变化

目的用体外实验方法研究1,2-二氯乙烷染毒后神经细胞形态学的变化。方法将体外培养的新生SD大鼠的脑皮质细胞,分为设对照组、低、中、高剂量组,观察各组细胞形态学、超微结构和细胞活力的变化。结果染毒后神经细胞形态和超微结构均发生明显变化：在荧光显微镜下随着染毒剂量的增高,细胞核由亮绿色变为桔红色,胞体胀大甚至消失;在透射电镜下染毒组神经细胞的细胞核核膜溶解消失,染色质聚集深染,线粒体和内质网等细胞器肿胀,崩解,且线粒体嵴排列紊乱甚至消失;各染毒组神经细胞活力比对照组有所下降,差异有统计学意义（P〈0．05）。结论1,2-二氯乙烷可以导致神经细胞水肿坏死,并且有剂量依赖关系,随着染毒剂量的增加神经细胞破坏程度越大。     

亚急性1,2-二氯乙烷中毒性脑病治疗体会

1,2.二氯乙烷(1,2-DCE)是工业上常用的有机溶剂,其毒性高,使用范嗣广,易发生中毒.亚急性1,2-DCE中毒起病隐匿,初期症状不典型,后期以中毒性脑病为主要表现,临床上往往会误诊为神经系统的其他疾病.现将我院收治的3例亚急性1,2-DCE中毒性脑病病例报告如下.     

CYP2E1和CYP1A1及白细胞介素-4基因多态性与三氯乙烯药疹样皮炎的关系

目的 研究代谢酶基因CYP2E1和CYP1A1以及白细胞介素(IL)-4的基因多态性与三氯乙烯(TCE)药疹样皮炎易感性的关系.方法 选择35例TCE药疹样皮炎病例作为病例组,选无皮肤损害的35名健康工人作为对照组.应用实时荧光定量聚合酶链反应(PCR)和TaqMan MGB探针技术,检测病例组和对照组CYP2E1、CYP1A1和IL-4基因的单核苷酸多态性(SNP),计算病例组和对照组的基因型与等位基因型频率.结果 CYP1A1基因(rs1048943)的SNP多态性检测结果显示,病例组G等位基因频率(37.1%)明显高于对照组,差异有统计学意义(P＜0.01);检测发现,病例组CYP2E1基因-1053 C→岬位点T等位基因频率(41.4%)明显高于对照组,差异有统计学意义(P＜0.01);对IL4基因588 C→岬位点(rs2243250)检测发现,病例组TT纯合突变频率(75.0%)明显高于对照组,差异有统计学意义(P＜0.01),T等位基因频率(87.5%)明显高于对照组,差异有统计学意义(P＜0.01).结论 CYP1A1、CYP2E1和IL-4基因的某些位点的改变可能与少数TCE敏感个体对接触TCE引起的超敏反应存在密切关系,CYP1A1、CYP2E1和IL-4的基因多态性可能是TCE药疹样皮炎患者易感性差异相关的遗传学因素之一.