甲状腺素对甲状腺功能减低大鼠子代脑组织中同源盒基因Nkx2.2表达的影响

摘要

目的:探讨妊娠不同时期补充不同剂量甲状腺素对甲状腺功能减低子代大鼠脑组织中同源盒基因Nkx2.2表达的影响.方法:选取1月龄Wistar大鼠240只,雌雄各半.将雌性大鼠随机分为对照组,甲状腺功能减低(甲低)组,甲低孕鼠妊娠1～17 d(妊早期甲低)补充甲状腺素高、中、低剂量组,甲低孕鼠妊娠18～20 d(妊晚期甲低)补充甲状腺素高、中、低剂量组共8组.各组均饲以低碘饲料,高、中、低剂量组每100 g体质量每天分别补充甲状腺素3.5、2.0、0.5μg.对照组饮用碘酸钾溶液,总碘摄人量相当于大鼠生理碘需要量,其余7组饮用去离子水.3个月后与正常雄性大鼠交配.分别于孕17 d、新生当天及生后20 d,取8组子代大鼠的间脑组织,采用实时荧光定量PCR法检测脑组织中Nkx2.2mRNA的表达量.结果:在孕17 d,甲低组的Nkx2.2mRNA表达水平低于对照组,其他6组均高于对照组;在新生当天和生后20 d,除孕晚期甲低补充甲状腺素中剂量组外,其他各组的Nkx2.2 mRNA表达水平均低于对照组;在生后20 d孕早期甲低补充甲状腺素低、中、高剂量组的Nkx2.2 mRNA表达水平与甲低组比较差别无统计学意义(P>0.05).结论:甲低孕鼠子代大鼠脑组织同源盒基因Nkx2.2的表达受补充甲状腺素剂量及孕期的影响.%Objective: To explore the efferts of thyroid hormone, given to the hypothyroidism pregnant rats, on the expression of homeobox gene Nkx2.2 in the offspring brain tissues. Methods: One hundred and twenty Wistar rats (female)were randomly divided into eight groups, control group, hypothyroidism group, hypothyroidism with pregnancy (1-17 d) + thyroid hormone (high, medium and low dosage) groups, and hypothyroidism with pregnancy (18-20 d) + thyroid hormone (high,medium and low dosage) groups. Rats were fed with Iow-iodine diet. According to 100 g of rat body weight, the concentrations of thyroid hormone for high, medium and low dosage were 3.5, 2.0, 0.5 μg/d. Rats of normal control group were given KIO3 solution, and rats of other groups were given deionized water. Rats were mated with normal male rats (n=120) after three months of feeding. The brain samples were taken from the 17-day fetal rats, new-born and 20-day-old offspring rats of different groups. The content of Nkx2.2 mRNA in ventral brain tissue was detected hy real-time fluorescence quantitative PCR techniques. Results: In the 17-day fetal rats, the expression level of Nkx2.2 mRNA was lower in low-iodine group than that of control group, but the level was higher in other 6 groups than that of control group. In the new-born and 20-day-old offspring rats, the expression of Nkx2.2 mRNA was lower in hypothyroidism groups than that of control group; except for the hypothyroidism with pregnancy (18-20 d) group supplied with medium dosage of thyroid hormone. There was no significant difference in the expression level of Nkx2.2 mRNA between 20-day-old offspring rats supplied with thyroid hormone (high, medium and low dosage) compared to that of hypothyroidism group (P ＞ 0.05). Conclusion: The expression of Nkx2.2 in offspring rats is highly related to the supply dosage and supply time of thyroid hormone in hypothyroidism pregnant rats.