目的 研究妊娠期甲状腺功能亢进对仔鼠海马损伤时空间学习能力的影响。方法 雌性SD大鼠用左甲状腺素钠灌胃制作甲状腺功能亢进症大鼠模型,随机分为正常对照组(N组),轻度甲亢组(A组),重度甲亢组(B组)。模型成功后雌鼠以2∶1比例与雄鼠合笼,A、B组雌鼠受孕后继续给予左甲状腺素钠灌胃,N组给予同等量生理盐水。测定仔鼠21 d和60 d血清FT₃,FT₄,TSH水平, Morris水迷宫检测其学习能力的改变,Western blotting技术观察仔鼠海马神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)的表达,并检测海马组织NO含量。结果 1)各时期A组、B组nNOS及海马组织NO含量较N组增高,B组nNOS、NO较A组增高(P<0.05);2)21 d时A组比N组的隐匿平台逃避潜伏期(escape latency,EL)明显延长(P<0.05),60 d时两组差异无统计学意义(P>0.05);而 B组比A组、N组的隐匿平台逃避潜伏期在各时期均明显延长(P<0.05)。结论 妊娠期甲亢可以引起仔鼠海马nNOS表达增高,NO水平上升,从而导致其认知功能发生变化。

Objective To observed the effect of pregnancy hyperthyroidism on spatial learning and memory in the rat offspring. Methods Female SD rats were randomly divided into normal control group (N group),mild hyperthyroidism group (A group),severe hyperthyroidism group (B group).The rat's hyperthyroidism model was established with levothyroxine sodium,then female rats and male rats were in one cage by 2∶1 ratio.After conception,levothyroxine sodium was continued giving to A and B group,N group received the same amount of saline.Thyroid function of rats offspring and Morris water maze test about their learning and memory ability were tested at 21^st day and 60^th day.The expression of neuronal nitric oxide synthase (nNos) was observed by western blotting technology,and the level of nitric oxide NO in the brain was tested. Results 1) The nNOS and NO of A and B groups were increased than N group,nNOS and NO of B group was increased than A group (P<0.05);2) The escape latency of group A was obviously prolong than that of group N in 21st day (P<0.05),but no difference between the two groups in 60th day (P>0.05).The escape latency of group B was obviously prolong in each phases than that in group A and N (P<0.05). Conclusion Pregnancy hyperthyroidism can increase neuronal nitric oxide synthase expression and the level of NO in the hippocampus of rat offspring, and cause rats offing cognitive dysfunction.