雌激素对急性一氧化碳中毒迟发性脑病的研究

刘勇; 王仲霞; 李虎年; 黄光庆; 赵旭; 尤志珺; 付守芝

doi:10.13201/j.issn.1009-5918.2015.04.011

雌激素对急性一氧化碳中毒迟发性脑病的研究

- 1. 湖北医药学院附属人民医院重症医学科(湖北十堰, 442000);
- 2. 香港大学深圳医院重症医学科;
- 3. 湖北医药学院附属人民医院医务处;
- 4. 湖北医药学院附属人民医院老年病科;
- 5. 武汉市第三医院急诊科
基金项目:
2009-2010年度湖北省科技厅自然科学基金（No：2006ABA339）；湖北省卫生厅科研项目（No：2009JX2B92）

详细信息

通讯作者: 付守芝,E-mail:fszfsz188@163.com

中图分类号: R-33

收稿日期: 2014-04-24

Early estrogen intervention has therapeutic effect on delayed neuropsychologic sequelae in acute carbon monoxide poisoning

- 1. ICU, Renmin Hospital Afflilited to Hubei University of Medicine, Shiyan 442000, China;
- 2. University of Hongkong Shenzhen Hospital;
- 3. Office of Medical Affairs, Renmin Hospital Afflilited to Hubei University of Medicine;
- 4. Department of Geriatrics, Renmin Hospital Afflilited to Hubei University of Medicine;
- 5. Department of Emergency, Wuhan Third Hospital

More Information

Corresponding author: FU Shouzhi, E-mail: fszfsz188@163.com

Received Date: 24 April 2014

摘要

摘要: 目的：研究雌激素干预对急性一氧化碳（CO）中毒迟发性脑病（DNS）的防治作用，探索有效的临床治疗手段。方法：选择成年Wistar雌性大鼠。腹腔注入CO（150 ml/kg）建立CO中毒DNS模型。存活大鼠随机分为对照组和雌激素组。中毒2~6周后水迷宫试验评估动物的智力状态，苏木精-伊红染色观察脑组织病理改变，TUNEL法检测脑组织细胞凋亡。结果：实验动物腹腔注入CO后出现智力下降，脑组织细胞凋亡明显，符合DNS表现。雌激素干预可显著改善模型动物智力，减轻脑组织病理损害，降低细胞凋亡率。雌激素主要通过抑制凋亡相关信号通道Bcl-2来实现对神经的保护作用。结论：早期雌激素干预可有效降低CO中毒DNS发病率，显著减轻CO中毒DNS损害程度。
- 一氧化碳中毒迟发性脑病 /
- 雌激素 /
- 细胞凋亡
Abstract: Objective: To investigate the effect of estrogen intervention on delayed neuropsychologic sequelae (DNS) in acute carbon monoxide (CO) poisoning.Method: Adult Wistar rats were selected and were infused CO (150 ml/kg) by intraperitoneal injection to build DNS model.The rats were radomly grouped.Group of Estrogen (5 μg/kg) were injected Estrogen (5 μg/kg)with 30 min after poisoning.Morris maze test was adopted to evaluate the intelligence of rats.The apoptosis rates in brain was detected by TUNEL staining.The expression levels of Bcl,ERK1/2 and P38 protein were determined with western blot analysis.Result: After CO infusing,poisoning rats showed intelligence decline,leukoence demyeliation and apoptosis increasing,which coincided to DNS.After early estrogen intervention,the intelligence,leukoence demyeliation,brain lesion and apoptosis rates were ameliorated significantly.Western blot showed the protein expression of Bcl significantly increased,while level of ERK1/2 and P38 had no signicantly difference.Conclusion: Early Estrogen intervention can effectively decrease the rates and alleviate the damage of DNS occur after acute CO poisoning.Its effects may be due to stimulating early expression of bcl-2 and ERK and inhibiteded P38 protein.
- delayed neuropsychologic sequelae /
- acute carbon monoxide poisoning /
- estrogen

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参考文献(20)

[1]	Guzman J A.Carbon monoxide poisoning[J].Crit Care Clin,2012,28:537-548.
[2]	邓文彬,韩超,急性CO中毒418例临床分析[J].中国热带医学,2007,7(4):534-535.
[3]	Hampson N B,Dunn S L,Yip F Y,et al.The UHMS/CDC carbon monoxide poisoning surveillance program:three-year data[J].Undersea Hyperb Med,2012,39:667-685.
[4]	Wu P E,Juurlink D N.Carbon monoxide poisoning[J].CMAJ,2014,186:611-611.
[5]	王耀宏,赵金垣,崔书杰,等.急性一氧化碳中毒迟发性脑病的动物模型制备研究[J].中国职业医学,2004,31(2):5-10.
[6]	Weaver L K.Hyperbaric oxygen therapy for carbon monoxide poisoning[J].Undersea Hyperb Med,2014,41:339-354.
[7]	Ritzel R M,Capozzi L A,McCullough L D.Sex,stroke,and inflammation:The potential for estrogen-mediated immunoprotection in stroke[J].Horm Behav,2012,63:238-253.
[8]	Liu S B,Zhao M G.Neuroprotective effect of estrogen:role of nonsynaptic NR2B-containing NMDA receptors[J].Brain Res Bull,2013,93:27-31.
[9]	Rusa R,Alkayed N J,Crain B J,et al.17beta-estradiol reduces stroke injury in estrogen-deficient female animals[J].Stroke,1999,30:1665-1670.
[10]	Manwani B,McCullough L D.Estrogen in ischaemic stroke:the debate continues[J].Eur J Neurol,2012,19:1276-1277.
[11]	Zhang L,Nair A,Krady K,et al.Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice[J].J Clin Invest,2004,113:85-95.
[12]	Piantadosi C A,Zhang J,Levin E D,et al.Apoptosis and Delayed Neuronal Damage after Carbon Monoxide Poisoning in the Rat[J].Exp Neurol,1997,147:103-114.
[13]	Taniwaki M.Chromosome and gene[J].Nihon Rinsho,2007,65:34-40.
[14]	Fulda S.Targeting apoptosis signaling pathways for anticancer therapy[J].Front Oncol,2011,1:23-23.
[15]	Garcia-Saez A J.The secrets of the Bcl-2 family[J].Cell Death Differ,2012,19:1733-1740.
[16]	Mamik M K,Ghorpade A.Src homology-2 domain-containing protein tyrosine phosphatase (SHP) 2 and p38 regulate the expression of chemokine CXCL8 in human astrocytes[J].PLoS One,2012,7:e45596.
[17]	Bachstetter A D,van Eldik L J.The p38 MAP kinase family as regulators of proinflammatory cytokine production in degenerative diseases of the cns[J].Aging Dis,2010,1:199-211.
[18]	Clarke D N,Al Ahmad A,Lee B,et al.Perlecan Domain V induces VEGf secretion in brain endothelial cells through integrin alpha5beta1 and ERK-dependent signaling pathways[J].PLoS One,2012,7:e45257.
[19]	Sagar D,Lamontagne A,Foss C A,et al.Dendritic cell CNS recruitment correlates with disease severity in EAE via CCL2 chemotaxis at the blood——brain barrier through paracellular transmigration and ERK activation[J].J Neuroinflammation,2012,9:245-245.
[20]	付守芝,刘勇,王家良,等.氙气防治一氧化碳中毒迟发性脑病的实验研究[J].中华急诊医学杂志,2008,17(5):487-490.