氢气吸入对脓毒症相关性脑病小鼠认知功能的影响  

Protective effects of inhaled hydrogen gas on cognitive function in mice with sepsis-associated encephalopathy

作　　者：刘玲玲[1] 谢克亮[1] 陈红光[1] 东晓晴 李媛[1] 于泳浩[1] 

机构地区：[1]天津医科大学总医院麻醉科 天津市麻醉学研究所,300052

出　　处：《中华医学杂志》2014年第40期3179-3183,共5页National Medical Journal of China

基　　金：国家自然科学基金（81071533,81101409）;天津市应用基础及前沿技术研究计划资助（11JCYBJC12900）;天津市卫生局资助项目（2011KZ10）

摘　　要：目的：评价氢气吸入对脓毒症相关性脑病小鼠认知功能的保护作用，并初步探讨其相关机制。方法雄性ICR小鼠84只，6～8周龄，体重20～25 g，随机数字表法分为4组：假手术组（ Sham）、假手术＋氢气组（ Sham＋H2）、脓毒症组（ Sepsis）和脓毒症＋氢气组（ Sepsis＋H2）。采用盲肠结扎穿孔法（ CLP）制备小鼠脓毒症模型。氢气治疗组于假手术或CLP后1 h和6 h时分别吸入2％氢气1 h。于假手术或CLP后24 h观察小鼠神经功能改变和脑组织海马CA1区神经元的病理改变，同时检测血清及海马组织中超氧化物歧化酶（ SOD）、过氧化氢酶（ CAT）、丙二醛（ MDA）、人8异前列腺素F2α（8-iso-PGF2α）的水平。于假手术或CLP后3、5、7、14 d通过Y-迷宫测试和条件恐惧测试检测各组小鼠认知功能的变化。结果与Sham组相比，Sepsis组小鼠神经功能显著下降，海马CA1区神经元明显受损，血清和海马组织中SOD和CAT活性明显降低， MDA和8-iso-PGF2α水平明显升高。 CLP后3、5、7、14 d，Sepsis组小鼠在新异臂的时间百分比明显减少，环境相关性僵直时间百分比也明显减少；与Sepsis组相比，Sepsis＋H2组小鼠神经功能显著改善，海马CA1区受损神经元减少，血清和海马组织中SOD和CAT活性明显升高， MDA和8-iso-PGF2α水平明显降低。 CLP后3、5、7、14 d， Sepsis组小鼠在新异臂的时间明显增加，环境相关性僵直时间百分比也明显提高。结论氢气可明显减轻脓毒症相关性脑病小鼠的海马神经元损伤，改善认知功能，其机制可能与提高机体抗氧化水平及降低氧化产物水平有关。Objective To evaluate protective effects of inhaled hydrogen gas （ H2 ） on cognitive function in a murine model of sepsis-associated encephalopathy （ SAE） .Methods A total of 84 male ICR mice, weighing 20-25 g, aged 6-8 weeks, were randomly divided into 4 groups of sham, sham＋H2 , sepsis and sepsis＋H2 .Sepsis was established by cecal ligation and puncture （ CLP） .Mice in sham＋H2 and sepsis＋H2 groups received 2% H2 inhalation for 1 h at 1 h and 6 h after sham operation or CLP operation respectively.The changes of neurological function and neuronal damage in hippocampal CA1 region were observed at 24 h post-operation.The activities of superoxide dismutase （ SOD） and catalase （ CAT） and the levels of malondialdehyde （ MDA ） and 8-iso-prostaglandin F2α（ 8-iso-PGF2α） in sera and hippocampus were detected at 24 h post-operation.The changes of cognitive function were observed by Y-maze test and fear conditional test at days 3 to 14 post-operation.Results Compared with sham group, the neurological function significantly declined and neurons in hippocampal CA1 region were significantly damaged;the activities of SOD and CAT markedly decreased while the levels of MDA and 8-iso-PGF2αmarkedly increased in sera and hippocampus; the time in new zone and the percentage of freezing time dramatically decreased at days 3 to 14 post-operation in sepsis group（P＆lt;0.05）.Compared with sepsis group, neurological function significantly improved and damaged neurons in hippocampal CA1 region significantly reduced;the activities of SOD and CAT markedly increased and the levels of MDA and 8-iso-PGF2αmarkedly decreased in sera and hippocampus; the time in new zone and the percentage of freezing time dramatically increased at days 3 to 14 post-operations in sepsis＋H2 group （P＆lt;0.05）.Conclusion H2 inhalation can significantly alleviate neuronal damage and improve cognitive dysfunction in CLP-induced SAE mice.And it is probably associated with the increased activities of antioxidant enzyme

关 键 词：氢 脓毒症 氧化性应激 认知 

分 类 号：R459.7[医药卫生—急诊医学]