氢气对慢性低氧高二氧化碳大鼠学习记忆障碍的干预作用

Intervention of hydrogen on memory damage induced by chronic hypoxia-hypercapnia in rats

目的:观察氢气(H2)对慢性低氧(O2)高二氧化碳(CO2)模型大鼠学习记忆的干预作用。方法:将通过八臂迷宫训练的24只清洁级雄性SD大鼠随机分为常氧对照组(NC)、低O2高CO2+生理盐水组(MS)、低O2高CO2+H2(MH),每组8只。NC组于常温常压条件下饲养,MS组和MH组置于O2浓度9%-11%和CO2浓度5%-6%的舱内饲养,每天8 h,每周6 d,持续4周,其余时间饲养条件与NC组相同。每天出舱后,MS组腹腔注射生理盐水,MH组腹腔注射饱和H2水,剂量均为5 mL/kg。4周后,八臂迷宫测试3组大鼠的学习记忆能力;酶联免疫吸附法检测海马8-羟基脱氧鸟苷(8-OHdG)含量;分光光度计检测血清超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量;显微镜下观察3组大鼠海马超微结构及神经元凋亡小体数量。结果:(1)与NC组比较,MS组和MH组工作记忆错误(WME)次数增加,海马8-OHdG和血清MDA含量增加,血清SOD活性降低,海马部位细胞结构排列紊乱,尼氏体形状和数量均有改变,凋亡细胞明显增多。(2)与MS组相比,MH组WME次数减少,海马8-OHdG和血清MDA含量降低,血清SOD活性增加,细胞结构较整齐,尼氏体丰富完整,凋亡神经元数量明显减少。结论:H2改善低O2高CO2大鼠学习记忆障碍,可能与减少神经元凋亡和氧化应激损伤有关。

AIM： To investigate the effects of hydrogen on the memory damage caused by chronic hypoxia-hypercapnia in rats.METHODS： Twenty-four SD rats trained by eight-arm radial maze test were randomly divided into 3 groups：normal control group（NC）,hypoxia-hypercapnia＋saline group（MS） and hypoxia-hypercapnia＋ hydrogen group（MH）.The rats in the latter 2 groups were placed in a closed cabin for 8 h/day,6 days/week and lasted for 4 weeks,in which O2 was 9%-11% and CO2 was 5%-6%.In every time after the animals were out of the cabin,the MS rats were intraperitoneally injected with saline（5 mL/kg） and the MH rats were intraperitoneally injected with hydrogen solution at the same dose.The learning and memory function,the activity of superoxide dismutase（SOD）,the content of malondialdehyde（MDA） and 8-hydroxydeoxyguanosine（8-OHdG） were examined after the cabin training.The ultramicrostructures of hippocampus were also observed.RESULTS： （1） Compared with NC group,the number of working memory errors,the total errors,the content of hippocampus 8-OHdG and serum MDA in MS and MH groups were higher and the activity of serum SOD was lower（P〈0.05）.The hippocampus structure was destroyed and some degree of edema and more apoptosis in the neurons were obserued in MS group and MH group.（2） Compared with MS group,the number of working memory errors（WME）,the total errors,the content of hippocampus 8-OHdG and serum MDA were lower and the activity of serum SOD was higher in MH group（P〈0.05）.In MH group,the morphology of hippocampus structures kept nearly normal arrangement and the only mild edema and fewer apoptosis in the neurons were found.CONCLUSION： Hydrogen may attenuate chronic hypoxia-hypercapnia-induced memory damage in rats by inhibiting apoptosis of the neurons and decreasing detrimental free radicals reaction.