慢性低O2高CO2对大鼠海马Bcl-2、Bax基因表达及细胞凋亡影响.doc

慢性低O2高CO2对大鼠海马Bcl-2、Bax基因表达及细胞凋亡影响 　【摘要】 目的:探讨慢性低O2高CO2对大鼠海马神经细胞凋亡的诱发作用及对Bcl-2、Bax基因表达的影响。方法:雄性SD大鼠50只，随机均分成5组：正常对照组（NC）、低O2高CO21周组（1HH）、2周组（2HH）、3周组（3HH）和4周组（4HH）。采用TUNEL法检测海马神经细胞凋亡；以RT-PCR检测海马Bcl-2 mRNA和Bax mRNA的表达。结果:随着低O2高CO2时间延长，凋亡指数(AI)及Bax mRNA水平进行性升高；Bcl-2 mRNA先升高后下降（均Plt;0.01）。AI与Bax mRNA之间呈显著正相关（r=0.814，Plt;0.01），而与Bcl-2 mRNA/Bax mRNA比值之间呈显著负相关（r=-0.405，Plt;0.01）。结论:慢性低O2高CO2可以诱发大鼠海马神经细胞凋亡，Bcl-2/Bax比值下降是促进凋亡的重要因素。 【关键词】 海马 低氧 高碳酸血症 凋亡 Bcl-2 Bax Abstract: Objective: To explore the inducing effect of chronic hypoxic hypercapnia on the apoptosis of rat neural cells in the hippocampus, and the relationship between the apoptosis and Bcl-2 as well as Bax gene expression. Methods: Fifty male spragu-dawley rats were randomly divided into five groups: normal control group (NC), hypoxic hypercapnia 1-week (1HH), 2-week (2HH), 3-week (3HH) and 4-week (4HH) group. The in situ cell apoptosis in the hippocampus was detected with TUNEL staining. The expression of Bcl-2 and Bax mRNA in the hippocampus were examined with RT-PCR. Results: Apoptosis index (AI) and the expression Bax mRNA were progressirely increased with the prolongation of duration of hypoxic hypercapnic exposure, and the expression of Bcl-2 mRNA was increased at first, then declined. There was a significant positive correlation between AI and the expression of Bax mRNA (r=0.814, Plt;0.01), and there was a significant negative correlation between AI and the ratio of Bcl-2 mRNA/Bax mRNA (r=-0.405, Plt;0.01). Conclusion: Apoptosis can be induced by chronic hypoxic hypercapnia in rat hippocampus. The ratio of Bcl-2/Bax decline accelerates the occurrence of apoptosis. Key words: hippocampus; hypoxia; hypercapnia; apoptosis; Bcl-2; Bax 临床上慢性阻塞性肺疾病（chronic obstruc-tive pulmonary disease，COPD）由于通气功能障碍常引起低氧血症或伴高碳酸血症，病情持续发展可导致肺性脑病。动物实验也发现，慢性低氧能够引起脑组织结构和功能的损害[1，2]，但迄今为止，其发生机制尚未完全阐明。近年来研究发现，细胞凋亡可能在慢性低氧性脑损害中起重要作用[3]。本实验采用慢性低O2高CO2性肺动脉高压大鼠模型，通过不同低O2高CO2干预时间（1周、2周、3周、4周），动态观察大鼠海马神经细胞凋亡及凋亡相关基因表达的变化，初步探讨慢性低O2高CO2大鼠海马神经