亚急性高原低氧对移居大鼠海马神经元凋亡和CA1区半胱天冬蛋白酶-3表达的影响  

Effects of Subacute High Altitude Hypoxia on Neuronal Apoptosis in Hippocampal and Expression of Caspase-3 in Hippocampus CA1 Subfield in Rats

作　　者：吴穹[1] 刘永年[1] 郭志坚 马祁生[1] 

机构地区：[1]青海大学医学院病理生理教研室,青海西宁810001 [2]青海省交通医院,青海西宁810001

出　　处：《环境与健康杂志》2010年第7期595-598,F0003,共5页Journal of Environment and Health

基　　金：交通部科研项目(200631800051);青海大学医学院科学技术研究项目(QY-2008-08)

摘　　要：目的初步探讨亚急性高原低氧对移居大鼠海马神经元凋亡和CA1区半胱天冬蛋白酶-3(Caspase-3)表达的影响及其机制。方法将48只清洁级健康成年Wistar雄性大鼠随机分为2组,低海拔对照组(海拔400m),亚急性高原组(海拔4300m);在不同海拔喂养30d后,取海马组织,利用流式细胞仪检测海马神经元凋亡率,通过免疫组织化学法观察CA1区神经元Caspase-3的表达变化,并测定海马组织MDA含量、SOD活力、Ca2+-ATP酶活力和钙含量。结果与低海拔对照组相比,亚急性高原组大鼠海马神经元凋亡率、CA1区神经元Caspase-3免疫组化阳性细胞数、MDA含量、钙含量均较高,而Ca2+-ATP酶活力降低,差异均有统计学意义(P<0.01)。两组SOD活力间差异无统计学意义。结论亚急性高原低氧可诱导移居大鼠海马神经元凋亡,其作用机制可能与其降低Ca2+-ATP酶活力、增加组织钙含量,使自由基含量升高有关。Objective To observe the effects of subacute high altitude hypoxia and the mechanisms on neuronal apoptosis in the hippoeampal and the expression of caspase-3 in hippoeampus CA1 subfield with in rats. Methods Forty-eight adult male Wistar rats were randomly divided into two groups and moved to different altitude environment （400 m, 4 300 m）, the animals were sacrificed by decapitation after thirty days. The flow cytometry was used to assay the ratio of apoptosis of hippocampal neurons. The expression of easpase-3 on hippocampal CA1 subfield were observed with immunohistochemistry. The content of malondialdehyde （MDA）,the activity of superoxide dismutase （SOD） in hippocampal tissue,the activity of Ca^2＋-ATPase and the Ca^2＋ content in hippocampal tissue were determined. Results Compared with low altitude control group,the ratio of apoptosis neurons and the neuronal number of up-regulated expression of easpase-3 in the hippocampus subfield significantly increased in the subacute high altitude groups, MDA contents and Ca^2＋ content in hippocampal tissue increased in the subacute high altitude groups, the activity of Ca^2＋-ATPase decreased. However, no significant difference was seen in SOD activity in hippocampal tissues of rats between the low altitude control and subacute high altitude groups. Conclusion Stress of high altitude hypoxia may induce the apoptosis of hippocampal neurons,maybe it is related to increased Ca^2＋ content by decreasing the activity of Ca^2＋-ATPase and increased free radical.

关 键 词：高海拔 低氧 海马 细胞凋亡 半胱天冬蛋白酶-3 

分 类 号：R994.6[医药卫生—毒理学]