AIM:To study the expression of p-p38 MAPK in partial cerebral tissues after hypoxic-ischemic brain damage (HIBD) in the neonatal adenosine A2A receptor knockout (A2AR-/- ) mice. METHODS; Base on the modified Rice method, the model of HIBD was established. The total 64 C57/BL6 neonatal mice (7 days old) of A2AR-/-(KO) and corresponding wild type (A2AR+/+ , WT) were randomized into sham-operated group and model group. The mice in model group were divided into 3 subgroups: 1 d after HIBD, 3 d after HIBD and 7 d after HIBD ( n = 8 for each group). The cortex and hippocampal CA1 region were used as the study areas. The neuronal apoptosis was detected using TUNEL assay combined with Nissl staining. The expression of p-p38 MAPK and activated caspase-3 was determined by the method of immunohistochemistry. The KO mice and WT mice were also taken from sham-operated group (SKO and SWT, n = 10) and model group (MKO and MWT, n =30) 1 d after HIBD to assess the early neurological behavior. RESULTS: The apoptotic neurons, activated caspase-3 and p-p38 MAPK increased after HIBD and peaked at 1 d after HIBD in the cortex and the hippocampal CA1 region. The apoptotic neurons and the expression of activated caspase-3 in KO mice were significantly higher than those in WT mice at the same time point after HIBD. The expression level of p-p38 MAPK in KO mice were significantly higher than that in WT mice at 1 d and 3 d after HIBD. The expression of activated caspase-3 was positively correlated with the expression of p-p38 MAPK in neonatal mice after HIBD (in the cortex; r = 0.957, P < 0. 01;in the hippocampal CA1 region: r =0.939, P <0. 01). CONCLUSION: p-p38 MAPK might be involved in the aggravated neuron apoptosis and brain damage induced by A2AR knockout after neonatal HIBO.%目的:探讨p-p38 MAPK在腺苷A2A受体敲除(A2AR-/-)新生小鼠缺氧缺血脑区的表达及意义.方法:采用改良Rice法建立新生小鼠缺氧缺血性脑损伤(HIBD)模型.A2AR-/-(KO)及同期野生型(A2AR+/+,WT) C57/BL6新生小鼠(7日龄)分别按照完全随机分组方法分成假手术组及模型组,模型组按HIBD后取标本时间不同又分为造模后1d组、3d组和7d组,共8个实验动物组,每组取小鼠8只,共64只.采用TUNEL结合尼氏染色检测神经细胞凋亡,采用免疫组织化学法检测活化caspase-3及p-p38 MAPK表达.同时,KO及同期WT小鼠分别取假手术组(SKO和SWT,n=10)及模型组(MKO和MWT,n=30)于HIBD后1d同时进行新生鼠短期神经行为学评定.结果:(1)缺氧缺血后皮层及海马CA1区神经细胞凋亡、活化caspase-3及p-p38 MAPK表达均增加,造模后1d为高峰；(2)A2AR敲除导致神经细胞凋亡及活化caspase-3表达增加,与同一时点的WT小鼠相比均有显著差异(P＜0.01)；p-p38 MAPK表达增加,其中,1d及3d后2种基因型小鼠间均有显著差异(P＜0.01)；(3)Peason相关分析显示,活化caspase-3表达与p-p38 MAPK表达呈显著正相关(皮层:r=0.957,P＜0.01；海马CA1区:r=0.939,P＜0.01).结论:p-p38 MAPK可能参与了A2AR敲除增加新生小鼠脑缺氧缺血后神经细胞凋亡、加重脑损害的过程.
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