摘要目的 研究低碘膳食对大鼠脑组织同源盒基因Nkx-6.1、Nkx-6.2 mRNA表达的影响,探讨低碘导致脑发育迟滞的可能分子作用机制.方法 20只雌性Wistar大鼠按体质量随机分为2组:低碘组和对照组,均饲以低碘饲料(含碘量为13.66 μg/kg),分别饮用去离子水和含碘200 μg/L的碘酸钾溶液,3个月时采用化学发光免疫分析法检测大鼠血清甲状腺激素水平,然后将雌鼠与正常饲养的Wistar雄鼠进行交配,分别取孕16 d、新生期及生后20日龄仔鼠脑组织,采用实时荧光定量PCR检测Nkx-6.1、Nkx-6.2 mRNA的表达.结果 ①低碘组大鼠血清TT3、TT4、FT3、FT4水平[(0.89±0.20)、(0.32±0.16)nmol/L,(3.33±0.61)、(3.28±0.80)pmol/L]均明显低于对照组[(1.04±0.06)、(39.42±14.68)nmoL/L,(4.83±0.33)、(26.99±4.48)pmol,t=2.71、6.52、5.70、12.89,P<0.05或<0.01].②对照组孕16 d、新生期及20日龄仔鼠脑组织Nkx-6.1 mRNA表达水平分别为(1.90±0.23)×10-3、(1.86±0.40)×10-4、(1.11±0.27)×10-4,各日龄间比较差异有统计学意义(F=827.58,P<0.01),随着日龄增加Nkx-6.1 mRNA表达水平明显下降,两两比较差异均有统计学意义(P均<0.01);低碘组各日龄仔鼠脑组织Nkx-6.1 mRNA表达水平分别为(1.16±0.16)×10-3、(3.44±0.49)×10-4、(3.58±0.64)×10-4,差异有统计学意义(F=297.25,P<0.01),但变化趋势与对照组不同,孕16 d表达水平最高,与新生期及20日龄比较,差异有统计学意义(P<0.01);低碘组与对照组比较,孕16 d明显降低(t=10.14,P<0.01).而新生期及20日龄则明显增高(t值分别为9.69、13.81,P均<0.01).③对照组和低碘组各日龄仔鼠脑组织Nkx-6.2 mRNA表达水平分别为(1.03±0.19)×10-2、(1.33±0.10)×10-3、(8.79±0.87)×10-2和(0.31±0.03)×10-2、(1.53±0.13)×10-3、(7.51±0.86)×10-2,组间比较差异有统计学意义(F值分别为1293.02、1065.83,P均<0.01),随着日龄增加,两组表达趋势一致,20日龄最高,孕16 d次之,新生期最低;低碘组20日龄仔鼠与新生期及孕16 d比较,差异有统计学意义(P均<0.01),对照组新生期仔鼠与孕16 d比较,差异有统计学意义(P<0.01);低碘组与对照组比较,孕16 d及20日龄明显降低(t值分别为14.35、4.05,P均<0.01),而新生期仔鼠则明显增高(t=4.78,P<0.01).结论 同源盒基因Nkx-6.1、Nkx-6.2mRNA表达水平改变可能与低碘导致脑发育迟滞有关.

abstractsObjective To study the influence of low-iodine diet on the expression of homeobox gene Nkx-6.1 and Nkx-6.2 in rat cerebrum tissue, and to explore the possible molecular mechanism of cerebrum development retardation caused by low-iodine. Methods Twenty female Wistar rats were randomly equally divided into two groups: low-iodine group and control group, both fed with low-iodine diet as low as 13.66 μg/kg determinated by spectrophotometry in Tianjin Institute of Endocrinology and the former with deionized water, the later 200 μg/L potassium iodate. Thyroid hormone level was detected using chemiluminescence immunoassay 3 months later and they were mated with male rats normally fed. Rats of 16-day pregnancy, new-born and 20th days old were detected the content of Nkx-6.1 and Nkx-6.2 mRNA in the cerebrum tissue by real-time fluorescence quantitative PCR 0.61), (3.28±0.80)pmol/L] were lower than the control group[(1.04±0.06), (39.42±14.68)nmol/L, (4.83±0.33), day pregnancy, new-born and 20th days old of control group was (1.90±0.23)×10-3,(1.86±0.40)×10-4, (1.11± 0.27)×10-4(F=827.58, P<0.01), Nkx-6.1 mRNA expression level gradually decreased along with aging(all P<0.05). The intra-group difference was significant (F=297.25, P<0.01) and the Nkxr.1 mRNA expression level during 16 days of pregnancy was the highest(P<0.01). It was higher in the control group than in the low-iodine group during 16 days of pregnancy (t=10.14, P<0.01) as well as in the low-iodine group than in the in 16-day pregnancy, new-born and 20th days old of control group was respectively(1.03±0.19)×10-2, (1.33± 0.10)×10-3, (8.79±0,87)×10-3, and that of low-iodine group was (0.31±0.03)×10-2, (1.53±0.13)×10-3, (7.51±0.86)×10-2. The intra-group difference was significant(F=1293.02,1065.83, all P<0.01). Nkx-6.2 expression level during 20th days old was the highest(P<0.01) and that of newborn was the lowest(P<0.01). The Nkx6.2 mRNA expression level in control group were higher than the low-iodine group during 16-day pregnancy and 20th days old(t=14.35, 4.05, all P<0.01). It was higher in the low-iodine group than in the control group during newboru(t=4.78, P<0.01). Conclusions The difference in the expression of Nkx-6.1 and Nkx-62 is highly related to the brain development retardation caused by low-iodine.