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目的:探讨咖啡因对慢性低O_2高CO_2处理的大鼠空间学习记忆、皮质和海马N-甲基-D-天冬氨酸受体(NMDAR)亚基1 mRNA(NR1 mRNA)表达的影响。方法:SD大鼠48只分为4组,正常对照组;低O_2高CO_24周(HH)组,处理组:低O_2高CO_2+咖啡因0.1 mg·mL~(-1)4周(HC1组),低O_2高CO_2+咖啡因0.3 mg·mL~(-1)4周(HC2组)。处理组以咖啡因水溶液干预4周后行Morris水迷宫实验,观察大鼠寻找站台的平均逃避潜伏期和游泳总距离;采用原位杂交法观察大鼠海马及皮质区NR1 mRNA的表达与分布情况。结果:①Morris水迷宫实验显示,HH组与对照组相比大鼠寻找站台的平均逃避潜伏期延长、游泳总距离增加(P<0.05),HC2组有显著性降低(P<0.05);②原位杂交显示NR1 mRNA阳性细胞广泛分布于海马和皮质区;模型组与对照组比较大鼠海马锥体细胞层NR1 mRNA表达的平均吸光度值降低(P<0.05),而咖啡因处理组平均吸光度值升高。结论:咖啡因可改善慢性低O_2高CO_2大鼠的空间学习记忆能力并增加海马和皮质区NR1 mRNA的表达。
Objective: To investigate the effect of caffeine on the spatial learning and memory, the expression of NMDAR subunit 1 mRNA (NR1 mRNA) in the cortex and hippocampus of rats with chronic low O_2 and high CO_2 treatment. Methods: Forty-eight SD rats were divided into 4 groups: normal control group, low O_2 high CO_24 week (HH) group, low O_2 high CO_2 + caffeine 0.1 mg · mL -1 for 4 weeks (HC1 group) , Low O_2 high CO_2 + caffeine 0.3 mg · mL -1 for 4 weeks (HC2 group). The rats in the treatment group were treated with aqueous caffeine solution for 4 weeks and Morris water maze test was performed to observe the mean escape latency and total swimming distance of the rats looking for platform. The expression and distribution of NR1 mRNA in hippocampus and cortex were observed by in situ hybridization. Results: (1) Morris water maze test showed that the mean escape latency of rats seeking platform was longer, the total distance of swimming increased (P <0.05) and the level of HC2 decreased significantly (P <0.05) in HH group compared with control group; Hybridization showed that NR1 mRNA positive cells were widely distributed in the hippocampus and cortex regions. Compared with the control group, NR1 mRNA expression in hippocampal pyramidal cells decreased (P <0.05) in model group and control group, while the average absorbance value high. CONCLUSION: Caffeine can improve spatial learning and memory ability and increase the expression of NR1 mRNA in hippocampus and cortex in chronic hypoxic hypercapnia rats.