【摘要】：胚胎期急性嚴(yán)重低氧常導(dǎo)致出生后運(yùn)動(dòng)失調(diào)、認(rèn)知功能障礙和精神發(fā)育異常,目前仍缺乏有效的預(yù)防治療手段。本研究旨在探討以世代為單位的中海拔低氧環(huán)境適應(yīng)是否對(duì)胚胎期急性嚴(yán)重低氧處理的小鼠有保護(hù)效應(yīng)。以在昆明(海拔約1 900 m)飼養(yǎng)繁殖一年半,傳代6~7代的ICR小鼠為研究對(duì)象,在妊娠9天(gestation day 9,GD 9)、13天(GD 13)或17天(GD 17)對(duì)孕鼠施加急性低氧處理(7%O_2,6 h),測(cè)試仔鼠出生后的發(fā)育情況、運(yùn)動(dòng)(曠場(chǎng))、空間學(xué)習(xí)記憶(水迷宮)和焦慮水平(高架十字迷宮),并對(duì)相關(guān)腦區(qū)進(jìn)行細(xì)胞計(jì)數(shù)。此外,還檢測(cè)了生活在中海拔和低海拔地區(qū)小鼠的血液學(xué)指標(biāo)。結(jié)果顯示:(1)中海拔低氧環(huán)境適應(yīng)良好的小鼠,其血液中的紅細(xì)胞計(jì)數(shù)(red blood corpuscle count,RBC)、血紅蛋白濃度(hemoglobin concentration,HBC)、紅細(xì)胞壓積(hematocrit,HCT)水平顯著高于低海拔地區(qū)同性別的小鼠;(2)低氧組仔鼠的空間學(xué)習(xí)記憶能力沒(méi)有損傷,并且GD 17組雌性仔鼠的空間記憶提取能力強(qiáng)于對(duì)照組;(3)低氧各組仔鼠均未見(jiàn)外觀畸形和運(yùn)動(dòng)能力受損;(4)胚胎期低氧未造成仔鼠伏隔核、杏仁核和海馬神經(jīng)元發(fā)生明顯壞死。以上結(jié)果提示中海拔低氧環(huán)境適應(yīng)良好的小鼠遭遇胚胎期急性嚴(yán)重低氧時(shí),其發(fā)育、運(yùn)動(dòng)和認(rèn)知功能障礙程度明顯輕于低海拔地區(qū)小鼠的,其保護(hù)機(jī)制可能是:經(jīng)過(guò)數(shù)代中海拔低氧環(huán)境適應(yīng),ICR小鼠血液中的HBC和HCT增加。本研究的這些新發(fā)現(xiàn)可能會(huì)為探討急性胚胎期低氧損傷作用和干預(yù)療法提供依據(jù)。
[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.
【作者單位】： 云南省藥物研究所云南白藥集團(tuán)股份有限公司創(chuàng)新研發(fā)中心云南省中藥和民族藥新藥創(chuàng)制企業(yè)重點(diǎn)實(shí)驗(yàn)室;阿姆斯特丹自由大學(xué)分子和細(xì)胞神經(jīng)生物學(xué)系神經(jīng)基因組學(xué)和認(rèn)知研究中心;昆明理工大學(xué)靈長(zhǎng)類(lèi)轉(zhuǎn)化醫(yī)學(xué)研究院;徐州醫(yī)科大學(xué)遺傳學(xué)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)
【分類(lèi)號(hào)】：R714

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