不同碘营养水平大鼠妊娠期甲状腺和胎盘胰岛素样生长因子-Ⅰ及转化生长因子-β1mRNA表达水平的研究

Rat insulin-like growth factor- Ⅰ and transforming growth factor-β1 mRNA expression in thyroid and placenta with different iodine intakes during pregnancy

目的 观察不同碘营养水平下大鼠妊娠期甲状腺和胎盘胰岛素样生长因子（IGF）-Ⅰ及转化生长因子（TGF）-β1 mRNA表达水平的变化.方法 雌性Wistar大鼠150只,体质量80～100g,按体质量随机分为5组,每组30只,分别饮用含碘50（对照组,NI）、0（低碘1组,LI1）、5（低碘2组,LI2）、3000（高碘1组,HI1）、10 000 μg/L（高碘2组,HI2）的去离子水.饲养12周将雌鼠同雄鼠合笼交配,分别于孕早期（第6、7天）,孕中期（第12、13天）、孕晚期（第19、20天）处死,取甲状腺及胎盘.利用实时荧光定量PCR方法测定大鼠甲状腺和胎盘的IGF-Ⅰ及TGF-β1 mRNA表达水平.结果 ①LI1组和LI2组甲状腺绝对质量[（12.17±5.41）×10-2、（3.54±1.21）×10-2g]均高于NI组[（2.05±0.50）×10-2 g,P均＜0.05]；HI1组、HI2组甲状腺绝对质量[（1.64±0.27）×10-2、（1.66±0.29）×10-2 g]与NI组比较,差异无统计学意义（P均＞0.05）.②大鼠甲状腺IGF-Ⅰ mRNA表达：孕早期,LI1组、LI2组（1.98±0.35、1.47±0.22）均高于NI组（1.01±0.18,P均＜0.01）,HI1组、HI2组（0.68±0.16、0.75±0.09）均低于NI组（P均＜0.05）；孕中期,HI2组（1.14±0.17）低于NI组（1.58±0.33,P＜ 0.01）；孕晚期,LI2组、HI2组（1.47±0.20、1.45±0.35）均低于NI组（2.20±0.37,P均＜0.01）.NI组,孕早期、孕中期、孕晚期的IGF-Ⅰ mRNA表达水平（1.01±0.18、1.58±0.33、2.20±0.37）呈增高趋势,任意两组间比较差异均有统计学意义（P均＜ 0.01）.③大鼠甲状腺TGF-β1 mRNA表达：孕早期,H1组（1.37±0.13）高于NI组（1.05±0.18,P＜ 0.01）,HI1组、HI2组（0.50±0.09、0.44±0.11）均低于NI组（P均＜0.01）；孕中期,LI1组LI2组（1.39±0.28、1.17±0.12）均高于NI组（0.63±0.22,P均＜0.01）；孕晚期,LI1组、LI2组（1.57±0.30、1.23±0.20）均高于NI组（0.68±0.17,P均＜0.01）.NI组孕中期、孕晚期（0.63±0.22、0.68±0.17）均低于孕早期（1.05±0.18,P均＜0.01）.④大鼠胎盘IGF-Ⅰ mRNA表达：孕中期,HI1组、HI2组（1.48±0.16、1.45±0.25）均高于NI组（1.00±0.10,P均＜0.01）；孕晚期,HI1组（1.75±0.15）高于NI组（1.54±0.29,P＜ 0.05）；HI2组（1.94±0.31）高于NI组（P＜0.01）.NI组孕晚期高于孕中期（P＜0.01）.⑤大鼠胎盘TGF-β1 mRNA表达：孕中期、孕晚期各组间比较差异均无统计学意义（P均＞0.05）；NI组孕晚期（0.83±0.16）低于孕中期（0.98±0.20,P＜ 0.05）.结论 妊娠期碘缺乏条件下甲状腺上调IGF-ⅠmRNA表达,这种作用在孕早期尤为显著；同时增高TGF-β1 mRNA表达,且此抑制作用随碘缺乏程度加深逐渐显著.碘过量情况下甲状腺IGF-Ⅰ、TGF-β1作用则相对较弱.随着孕程增长胎盘组织中IGF-Ⅰ发挥促进组织生长分化的作用逐渐显著,相反TGF-β1的抑制作用则减弱.

Objective To study the mRNA expression of rat Insulin-like growth factors- Ⅰ （IGF- Ⅰ ） and Transforming growth factor-β1 （TGF-β1） in thyroid and placenta with different iodine intakes during pregnancy.Methods One hundred and fifty female Wistar rats,weighting 80 - 100 g,were randomly divided into five groups according to body weight,30 rats in each group.Each group was given deionized water containing different concentrations of iodine,50 μg/L（control group,NI）,0 μg/L（iodine deficiency 1 group,LI1 ）,5 μg/L（iodine deficiency 2 group,LI2）,3000 μg/L（iodine excess 1 group,HI1 ）,and 10 000 μg/L（iodine excess 2 group,HI2）,respectively.After feeding for 12 weeks,the female rats were mated with male rats.The female rats were sacrificed at first（6,7 days）,trimester（ 12,13 days）,and third trimesters（ 19,20 days）,respectively,then their thyroid and placenta were collected.The mRNA expressions of IGF- Ⅰ and TGF-1 in thyroid and placenta were detected by real-time quantitative PCR.Results ①The actual thyroid weights of LI1 and LI2 groups[ （12.17 ± 5.41 ） × 10-2 g,（3.54 ± 1.21） × 10-2 g] were significantly higher than that of NI group[ （2.05 ± 0.50） × 10-2 g,all P 〈 0.05] ;actual weights of HI1 and HI 2 groups[ （1.64 ± 0.27） × 10-2 g,（1.66 ± 0.29） × 10-2 g] were compared with that of NI group,the difference was not statistically significant（all P 〉 0.05）.②The mRNA expression of IGF- Ⅰ： at the first trimester,LI1 and LI2 groups（l.98 ± 0.35,1.47 ± 0.22） were all higher than that of NI group（1.01 ± 0.18,all P〈 0.01 ）,HI1 and HI2 groups（0.68 ± 0.16,0.75 ± 0.09） were lower than that of NI group（all P 〈 0.01 ）;at the second trimester,HI2 group（ 1.14 ± 0.17） was lower than that of NI group（ 1.58 ± 0.33,P 〈 0.01 ） ; at the third trimester,LI2 and HI2 groups（1.47 ± 0.20,1.45 ± 0.35） were lower than that of NI group（2.20 ± 0.37,all P〈0.01）.The mRNA expression of IGF- I level in NI group at the first,second,and third trimesters（1.01 ±0.18,1.58 ±0.33,2.20 ± 0.37） was up regulated gradually,pairwise comparisons were statistically significant（all P 〈 0,01 ）.③The mRNA expression of TGF-β1： at the first trimester,LI1 group （1.37 ± 0.13） was higher than NI group （1.05 ±0.18,P 〈 0.01 ）,HI1 and HI2 groups（0.50 ± 0.09,0.44 ± 0.11） were lower than NI group（all P〈 0.01）; at the second trimester,LI1 and HI2 groups（1.39 ± 0.28,1.17 ± 0.12） were higher than NI group（0.63 ± 0.22,all P 〈0.01 ） ; at the third trimester,LI1 and LI2 groups （ 1.57 ± 0.30,1.23 ± 0.20） were higher than NI group （ 0.68 ± 0.17,all P〈 0.01）.TGF-β1 mRNA expressions of NI group at the second （0.63 ± 0.22） and third trimesters（0.68 ± 0.17） were lower than that of the first trimester （1.05 ± 0.18,all P 〈 0.01）.④ Rats＇ IGF-Ⅰ mRNA expression in placental： at the second trimester HI1 group,HI2 group（ 1.48 ± 0.16,1.45 ± 0.25） were all higher than the NI group （ 1.00 ± 0.10,all P 〈 0.01 ） ; at third trimester,HI1 group （ 1.75 ± 0.15 ） were higher than the NI group （ 1.54 ± 0.29,P〈 0.05）,HI2 group（l.94 ± 0.31） were higher than the NI group（P 〈 0.01 ）.IGF- Ⅰ mRNA expression in placental of NI group at the third trimester was higher than the second trimester（P〈 0.01）.⑤ Rats＇ TGF-β1 mRNA expression in the placenta： at the second trimester and the third trimester of pregnancy there were no significant difference between the five groups（all P 〉 0.05） ; NI group at the third trimester（0.83 ± 0.16） was lower than the second trimester（0.98 ± 0.20,P 〈 0.05）.Conclusions During pregnancy,IGF- I mRNA expression increases in thyroid under the conditions of iodine deficiency,and this effect is particularly significant in the first trimester; at the same time,TGF-β1 mRNA expression is increased,and this inhibition becomes clear with the deepening of iodine deficiency.Under the condition of iodine excess,the functions of IGF- Ⅰ and TGF-β1 in thyroid above-mentioned were relatively weak.With the development of gestational period,promoting tissues growth and differentiation effect of placenta＇s IGF- Ⅰ was more significant gradually,but,inhibited effect of TGF-β1 was weaken.