脑海马HO-1持续过表达在急性CO中毒迟发性脑病中的作用  

Role of persistent over-expression of HO-1 in hippocampus of rats with delayed encephalopathy after acute carbon monoxide poisoning

作　　者：关里[1] 张雁林[1] 毛丽君[1] 丛翠翠[1] 赵金垣[1] 

机构地区：[1]北京大学第三医院职业病研究中心,北京100191

出　　处：《中国工业医学杂志》2014年第4期264-268,305,F0003,共7页Chinese Journal of Industrial Medicine

基　　金：国家自然科学基金资助项目(HO-1/CO系统在急性一氧化碳中毒迟发性脑病中的致病作用研究;编号:81101024);北京市自然科学基金资助项目(血红素加氧酶-1异常表达对急性CO中毒迟发性脑病致病作用研究;编号:7113175)

摘　　要：目的研究血红素加氧酶-1(HO-1)持续性过表达对急性一氧化碳(CO)中毒大鼠脑海马的损伤作用。方法随机将大鼠分为4组,即空气对照组、急性CO染毒组、氯化高铁血红素(hemin)+CO组、锡原卟啉(SnPP)+CO组。在染毒10 d后检测各组海马HO-1表达和活性,丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性、caspase-3表达及活性变化,观察海马形态学变化。结果 CO染毒组大鼠海马HO-1呈持续性高表达,hemin可进一步诱导染毒大鼠海马HO-1表达,还能加重染毒大鼠海马氧化损伤和细胞凋亡,表现为CA1区、DG区锥体细胞和颗粒细胞坏死数量较CO染毒组分别增加39%和33%。用SnPP抑制HO活性对CO染毒脑组织有明显的保护作用,表现为海马氧化损伤和细胞凋亡减轻,CA1区、DG区锥体细胞和颗粒细胞坏死数量较CO染毒组均下降15%。结论 HO-1持续过表达可加重CO中毒引起的大鼠海马损伤,提示HO系列过表达在急性CO中毒迟发性脑损伤的病理过程中可能具有重要作用;其损伤机制可能与其加重脂质过氧化反应和细胞凋亡有关。Objective To explore the role of HO-1 persistent over-expression in hippocampus of rats with delayed encepha- lopathy after acute carbon monoxide poisoning. Methods Experimental animal were divided to four groups as follows ~ （ l ） con- trol group, （2） CO exposure group, （3） heroin ＋ CO exposure group, and （4） SnPP ＋ CO exposure group. The levels of malondialdehyde （MDA） and caspase-3, activities of SOD, and the expression of HO-1 in hippocampus of rats at the 10th day after CO exposure. Results There was a persistent over-expression of HO-1 in hippocampus of rats after CO exposure; hemin could further induce HO-1 expression, aggravate the hippocarnpal injury and apoptosis. Compared to the control group, the nec- rotic number of pyramidal and granular cell in CA1 and DG region was increased 39% and 33% , respectively. SnPP, the in- hibitor of HO, showed a protective effect on hippocampus after CO exposure. The study found that in SnPP group, oxidative damage and apoptosis were all reduced in hippocampus of rats, the number of necrotic neurons also decreased 15% in CA1 and DG region compared to CO exposed group. Conclusion The results showed that persistent over expression of HO-1 could aggravate hippocarnpal damage in the rats after CO exposure. It suggested that HO system might play an important role in delayed eneepha- lopathy after acute carbon monoxide poisoning, the persistent over-expression of HO-1 might be associated with increased lipid per- oxidation and cell apoptosis.

关 键 词：急性一氧化碳中毒迟发性脑病 血红素加氧酶 海马 过表达 丙二醛(MDA) 半胱氨酸天门冬氨酸蛋白酶-3(caspase-3) 

分 类 号：R595.1[医药卫生—内科学] R994[医药卫生—临床医学]