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目的:观察敲除腺苷An 2A受体基因对慢性低On 2高COn 2模型小鼠前额叶皮质细胞凋亡以及磷酸化p38丝裂原活性蛋白激酶(p-p38MAPK)蛋白表达的影响。n 方法:采用随机数字表法将16只腺苷An 2A受体野生型(+/+)小鼠和16只腺苷An 2A受体基因敲除型(-/-)小鼠各分为2个亚组，分别是对照-野生基因组、4周低On 2高COn 2-野生基因组(简称模型-野生基因组)、对照-基因敲除组、4周低On 2高COn 2-基因敲除组(简称模型-基因敲除组)，每组各8只小鼠。将模型-野生基因组、模型-基因敲除组小鼠置于常压低On 2高COn 2动物舱内，舱内On 2浓度维持在9%～11%水平，COn 2浓度维持在5.5%～6.5%水平，每天干预8 h，每周干预6 d，持续干预4周。于4周制模结束后采用原位末端标记法(TUNEL)检测各组小鼠前额叶皮质细胞凋亡情况，采用蛋白免疫印迹法检测各组小鼠前额叶皮质磷酸化p38MAPK蛋白表达水平。n 结果:两模型亚组前额叶皮质凋亡细胞数量均较相应的对照亚组明显增加(n P<0.05)，并且模型-野生基因组皮质凋亡情况较模型-基因敲除组更显著(n P<0.05)；两模型亚组前额叶皮质p-p38MAPK蛋白表达均较相应的对照亚组明显上调(n P<0.05)，并且模型-野生基因组p-p38MAPK蛋白表达上调幅度较模型-基因敲除组更显著(n P<0.05)。n 结论:敲除腺苷An 2A受体基因能抑制慢性低On 2高COn 2模型小鼠前额叶皮质p38MAPK信号转导通路活化，减少前额叶皮质神经细胞凋亡，为改善慢性阻塞性肺疾病(COPD)患者认知功能提供更多实验依据。n “,”Objective:To observe the effect of genetic inactivation of adenosine An 2A receptor on apoptosis in the prefrontal cortex and on the expression of phosphorylated p38 mitogen-active protein kinase (p38MAPK) in mice with chronic hypoxic hypercapnia.n Methods:Sixteen male wild-type mice and 16 male mice in which the adenosine An 2A receptor gene had been knocked out were randomly divided into a 4 weeks group (including 4HH+ /+ and 4HH-/- subgroups) and a normal control group (including NC+ /+ and NC-/- subgroups). The 4HH+ /+ and 4HH-/- group mice were exposed to an atmosphere containing 9-11% On 2 and 5-6% COn 2 8 hours a day, 6 days a week for 4 weeks. The apoptosis index (AI) in their prefrontal cortices was then evaluated using terminal-deoxynucleoitide transferase mediated nick end labelling (TUNEL) staining. The expression of p38MAPK protein in the prefrontal cortices was measured using western blotting.n Results:The average AI had increased significantly in the 4HH+ /+ and 4HH-/- groups compared with the controls, with significantly more apoptotic cells in the 4HH+ /+ group than in the 4HH-/- group. In the 4HH+ /+ and 4HH-/- groups the average expression of p38 protein in the prefrontal cortex was significantly higher than among their controls. Moreover, the average expression of p-p38MAPK protein in the prefrontal cortex of the 4HH-/- group was significantly lower than in the 4HH+ /+ group.Conclusion:Adenosine An 2A receptor knockout inhibits apoptosis in the prefrontal cortex and down-regulates the p38MAPK activation of mice after exposure to chronic hypoxic hypercapnia.n