甲状腺激素对仔鼠大脑皮质中NO/cGMP信号转导通路的作用

Effects of thyroid hormone on NO/cGMP signaling pathway of the neonat al rat cortex

目的研究甲状腺激素对大鼠仔鼠大脑皮质中一氧化氮(NO)水平、一氧化氮合酶(NOS)活性和环鸟苷酸(cGMP)水平的影响,为探讨甲状腺激素对神经系统发育的作用机制提供实验资料。方法取怀孕3d的SD大鼠10只,随机分为实验组与对照组。实验组饮含1%高氯酸钠的自来水,对照组饮自来水,直至仔鼠产下15d(其产下的仔鼠分别为甲状腺功能低下仔鼠及正常仔鼠)。采用放射免疫法测定仔鼠血清中游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)和仔鼠大脑皮质cGMP水平,采用硝酸还原酶法测仔鼠大脑皮质中NO水平,采用分光光度计法测NOS活性。结果实验组仔鼠血清FT3、FT4明显低于对照组(P<0.01)。实验组仔鼠大脑皮质中NO水平、NOS活性及cGMP水平也较对照组显著降低(P<0.01)。相关分析表明:血清FT3与大脑皮质中NO、cGMP水平呈显著正相关,r值分别为0.91、0.97,P<0.01;血清FT4与大脑皮质中NO、cGMP水平也呈显著正相关,r值分别为0.90、0.96,P<0.01;大脑皮质中NO与cGMP水平呈显著正相关,r值为0.90,P<0.01。结论甲状腺激素的缺乏可降低仔鼠大脑皮质中NO、cGMP水平,NO/cGMP信号转导系统在甲状腺功能低下导致脑发育障碍中发挥重要作用。

Objective To investigate the effects of thyroid hormone(TH) on nitr ic oxide(NO) contents, nitric oxide synthase(NOS) activity and cyclic guanosine monophosphate(cGMP) contents in the cortex of neonatal rats. Methods Ten SD preg nant rats were divided randomly into hypothyroidism group and control group. The animals had drunk water with 1% sodium perchlorate and normal water respectivel y from the 3rd embryonic day to the 15th day after childbirth. The newborn rats were perinatal hypothyroidism and normal neonatal rats respectively. FT3, FT4 an d cGMP contents were measured with radioimmunoassay. NOS activity and NO content s were assessed with spectrophotometric analysis. Results The serum FT3 and FT4 were significantly decreased in hypothyroid rats as compared to those in normal controls(P < 0.01). The NO, NOS and cGMP contents in the cortex of neonatal rats were lower in hypothyroidism rats than those in controls(P < 0.01). Both serum FT3 and serum FT4 positively correlated with cortex NO and cGMP(P < 0.01). There was also a positive correlation between cortex NO and cGMP(P < 0.01). Conclusio ns The lack of thyroid hormone can decrease the contents of NO and cGMP in th e neonatal rat cortex. NO/cGMP signaling pathway may play an important role in t he course of brain development regulated by thyroid hormone.