妊娠期甲状腺功能减退对大鼠子代认知功能的影响

Effect of hypothyroidism in pregnancy on cognitive function in rat offspring

目的通过实验性甲减妊娠大鼠模型的建立,初步探讨妊娠期甲减和药物干预对大鼠子代认知功能的影响。方法选取SD雌性大鼠20只随机分为对照组(CON组)和甲减组(PTU组),采用丙硫氧嘧啶(PTU)建立甲减模型,电化学发光免疫法检测雌鼠甲状腺激素水平,比较两组指标差异。造模成功后与雄鼠合笼交配,将甲减组孕鼠再随机分为孕期未干预组(Ⅰ组)、孕早期干预组(Ⅱ组)和孕中晚期干预组(Ⅲ组)。通过莫里斯水迷宫(MWM)实验测试仔鼠学习记忆能力。通过苏木精伊红染色(HE)、尼氏染色及免疫组化观察仔鼠海马神经元的形态结构、成熟神经元核蛋白(NeuN)和突触相关蛋白(SYN)的表达情况。结果①PTU组雌鼠较CON组TSH显著增高、FT4显著减低(P<0.05)。②在定位航行试验中,各组仔鼠到达平台的躲避潜伏期均表现逐渐缩短。第5天,Ⅰ组仔鼠到达平台的潜伏期较CON、Ⅱ、Ⅲ组明显延长(P<0.05);Ⅱ、Ⅲ组与CON组变化不大(P>0.05)。③空间探索阶段Ⅱ组仔鼠的滞留时间与Ⅰ组相比有明显差异(P<0.05);I组的仔鼠穿越平台次数与CON、II、III组有明显差异(P<0.05)。④各组仔鼠海马组织HE染色和尼氏染色无明显差异。但与CON组相比,Ⅰ、Ⅱ、Ⅲ组仔鼠海马组织NeuN、SYN蛋白的平均吸光度值均显著降低(P<0.05)。结论甲状腺功能减退对妊娠大鼠子代认知功能及海马神经元发育会产生不良影响,孕期不同阶段干预对子代认知功能的影响不同,干预越早,对认知功能的损伤越小。

Objective To investigate the effects of hypothyroidism and drug intervention on the cognitive function of rat offspring through the establishment of a rat model of experimental hypothyroidism in pregnancy.Methods A total of 20 SD female rats were randomly divided into control group(CON group)and hypothyroid group(PTU group).The hypothyroid model was established by propylthiouracil(PTU),the thyroid hormone levels of female mice were detected by electrochemiluminescence immunoassay,and the differences between the two groups were compared.After successful modeling,the male mice were mated in cages,and the hypothyroid group was randomly divided into no intervention group(group I),first trimester intervention group(group II)and second and third trimester intervention group(group III).The Morris water maze(MWM)experiment was used to test the learning and memory ability of the rats.The morphological structure of hippocampal neurons,the expression of nucleoprotein(NeuN)and synapse-associated protein(SYN)in mature neurons were observed by hematoxylin-eosin staining(HE),Nissl staining and immunohistochemistry.Results①Compared with the CON group,the female mice in the PTU group had a significant increase in TSH and a significant decrease in FT4(P<0.05).②In the positioning navigation test,the evasion latency of the pups in each group was gradually shortened.On the 5th day,the incubation period of group I was significantly longer than that of groups CON,II,III(P<0.05).There was little change between groups II and III and CON groups(P>0.05).③The residence time of group II was significantly different from that in group I during the space exploration stage(P<0.05).There was a significant difference between the number of pups crossing the platform in group I and groups CON,II and III(P<0.05).④There was no significant difference between HE staining and Nissl staining in hippocampal tissues of rats in each group.However,compared with the CON group,the average absorbance of NeuN and SYN proteins in the hippocampus of mice in groups I,II and III was significantly reduced(P<0.05).Conclusion Hypothyroidism will have adverse effects on the cognitive function and hippocampal neuron development of pregnant rats,and the effects of intervention on the cognitive function of offspring at different stages of pregnancy are different,the earlier the intervention,the smaller the damage to cognitive function.