中海拔低氧环境适应缓解小鼠胚胎期急性低氧造成的发育和认知损伤（英文）
发布时间：2018-11-02 19:19
【摘要】：胚胎期急性严重低氧常导致出生后运动失调、认知功能障碍和精神发育异常,目前仍缺乏有效的预防治疗手段。本研究旨在探讨以世代为单位的中海拔低氧环境适应是否对胚胎期急性严重低氧处理的小鼠有保护效应。以在昆明(海拔约1 900 m)饲养繁殖一年半,传代6~7代的ICR小鼠为研究对象,在妊娠9天(gestation day 9,GD 9)、13天(GD 13)或17天(GD 17)对孕鼠施加急性低氧处理(7%O_2,6 h),测试仔鼠出生后的发育情况、运动(旷场)、空间学习记忆(水迷宫)和焦虑水平(高架十字迷宫),并对相关脑区进行细胞计数。此外,还检测了生活在中海拔和低海拔地区小鼠的血液学指标。结果显示:(1)中海拔低氧环境适应良好的小鼠,其血液中的红细胞计数(red blood corpuscle count,RBC)、血红蛋白浓度(hemoglobin concentration,HBC)、红细胞压积(hematocrit,HCT)水平显著高于低海拔地区同性别的小鼠;(2)低氧组仔鼠的空间学习记忆能力没有损伤,并且GD 17组雌性仔鼠的空间记忆提取能力强于对照组;(3)低氧各组仔鼠均未见外观畸形和运动能力受损;(4)胚胎期低氧未造成仔鼠伏隔核、杏仁核和海马神经元发生明显坏死。以上结果提示中海拔低氧环境适应良好的小鼠遭遇胚胎期急性严重低氧时,其发育、运动和认知功能障碍程度明显轻于低海拔地区小鼠的,其保护机制可能是:经过数代中海拔低氧环境适应,ICR小鼠血液中的HBC和HCT增加。本研究的这些新发现可能会为探讨急性胚胎期低氧损伤作用和干预疗法提供依据。
[Abstract]:Severe acute hypoxia in embryonic stage often leads to postnatal motor disorder, cognitive dysfunction and mental dysplasia. At present, there is still a lack of effective preventive treatment. The purpose of this study was to investigate the protective effects of generation-to-generation hypoxia adaptation on mice treated with acute severe hypoxia at embryonic stage. ICR mice were bred in Kunming (about 1 900 m above sea level) for one and a half years and were subcultured for 6 ~ 7 generations. (gestation day 9GD9 was used as the study object on the 9th day of gestation. GD (GD 13) or GD 17 (acute hypoxia treatment) were administered to pregnant rats (7 / 10) to test postnatal development, exercise (open field), Spatial learning and memory (water maze) and anxiety level (elevated cross maze), and the related brain areas were counted. In addition, hematological indices of mice living at middle and low altitudes were also tested. The results showed that: (1) the red blood cell count (red blood corpuscle count,RBC), hemoglobin concentration (hemoglobin concentration,HBC), hematocrit (hematocrit,) in the blood of the mice with good adaptation to the hypoxic environment at mid-altitude were obtained. The level of HCT was significantly higher than that of mice of the same sex at low altitude. (2) the ability of spatial learning and memory was not damaged in hypoxia group, and the ability of spatial memory extraction in GD 17 group was stronger than that in control group, (3) the appearance deformity and motor ability were not impaired in hypoxia group. (4) hypoxia did not cause obvious necrosis of nucleus accumbens, amygdala and hippocampal neurons. The above results suggest that the developmental, motor and cognitive dysfunction of mice with moderate and high altitude and good adaptation to hypoxic environment is significantly less than that of mice at low altitude when they are exposed to acute and severe hypoxia at embryonic stage. The protective mechanism may be that HBC and HCT in the blood of ICR mice increased after several generations of hypoxic adaptation at mid-altitude. These findings may provide evidence for the study of acute embryonic hypoxic injury and intervention therapy.
【作者单位】： 云南省药物研究所云南白药集团股份有限公司创新研发中心云南省中药和民族药新药创制企业重点实验室;阿姆斯特丹自由大学分子和细胞神经生物学系神经基因组学和认知研究中心;昆明理工大学灵长类转化医学研究院;徐州医科大学遗传学系;
【基金】：supported by the Major Scientific and Technological Special Project of Yunnan Province,China(No.2015ZJ004) the Special Fund for Science and Technology Cooperation of Hainan Province,China(No.KJHZ2015-20)
【分类号】：R714
本文编号：2306721
[Abstract]:Severe acute hypoxia in embryonic stage often leads to postnatal motor disorder, cognitive dysfunction and mental dysplasia. At present, there is still a lack of effective preventive treatment. The purpose of this study was to investigate the protective effects of generation-to-generation hypoxia adaptation on mice treated with acute severe hypoxia at embryonic stage. ICR mice were bred in Kunming (about 1 900 m above sea level) for one and a half years and were subcultured for 6 ~ 7 generations. (gestation day 9GD9 was used as the study object on the 9th day of gestation. GD (GD 13) or GD 17 (acute hypoxia treatment) were administered to pregnant rats (7 / 10) to test postnatal development, exercise (open field), Spatial learning and memory (water maze) and anxiety level (elevated cross maze), and the related brain areas were counted. In addition, hematological indices of mice living at middle and low altitudes were also tested. The results showed that: (1) the red blood cell count (red blood corpuscle count,RBC), hemoglobin concentration (hemoglobin concentration,HBC), hematocrit (hematocrit,) in the blood of the mice with good adaptation to the hypoxic environment at mid-altitude were obtained. The level of HCT was significantly higher than that of mice of the same sex at low altitude. (2) the ability of spatial learning and memory was not damaged in hypoxia group, and the ability of spatial memory extraction in GD 17 group was stronger than that in control group, (3) the appearance deformity and motor ability were not impaired in hypoxia group. (4) hypoxia did not cause obvious necrosis of nucleus accumbens, amygdala and hippocampal neurons. The above results suggest that the developmental, motor and cognitive dysfunction of mice with moderate and high altitude and good adaptation to hypoxic environment is significantly less than that of mice at low altitude when they are exposed to acute and severe hypoxia at embryonic stage. The protective mechanism may be that HBC and HCT in the blood of ICR mice increased after several generations of hypoxic adaptation at mid-altitude. These findings may provide evidence for the study of acute embryonic hypoxic injury and intervention therapy.
【作者单位】： 云南省药物研究所云南白药集团股份有限公司创新研发中心云南省中药和民族药新药创制企业重点实验室;阿姆斯特丹自由大学分子和细胞神经生物学系神经基因组学和认知研究中心;昆明理工大学灵长类转化医学研究院;徐州医科大学遗传学系;
【基金】：supported by the Major Scientific and Technological Special Project of Yunnan Province,China(No.2015ZJ004) the Special Fund for Science and Technology Cooperation of Hainan Province,China(No.KJHZ2015-20)
【分类号】：R714
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