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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21d和60d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)21d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),60d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 study the effect of hyperthyroidism during gestation on the spatial learning ability of hippocampus in neonatal rats. Methods Female SD rats were treated with levothyroxine sodium for hyperthyroidism rats and randomly divided into normal control group (N group), mild hyperthyroidism group (A group) and severe hyperthyroidism group (B group). After the success of the model, the females were caged with the male rats in a ratio of 2: 1, and females in groups A and B continued to be given sodium levothyroxine after conception, and the rats in group N were given the same amount of normal saline. The levels of FT3, FT4 and TSH were measured at 21d and 60d in the offspring. The changes of learning ability were detected by Morris water maze. The expression of neuronal nitric oxide synthase (nNOS) in the hippocampus was observed by Western blotting, The content of NO in hippocampus was detected. Results 1) The content of NO in nNOS and hippocampus of group A and group B was higher than that of group N in each period, and the level of nNOS and NO in group B was higher than that of group A (P <0.05); 2) The hidden platform escape latency (P <0.05). However, there was no significant difference between the two groups on the 60th day (P> 0.05), while the escape latency of the hidden platform in group B was significantly longer than that in group A and group N P <0.05). Conclusions Hyperthyroidism during pregnancy can induce nNOS expression in hippocampus of hippocampus and increase the level of NO, which leads to the change of cognitive function.