【摘要】 目的探讨母源性甲亢对仔鼠甲状腺功能及肝组织Caspase-3、Bcl-2表达的影响。方法将36只SD雌鼠随机分为对照组、低剂量左甲状腺素钠组、高剂量左甲状腺素钠组各12只。低剂量左甲状腺素钠组给予左甲状腺素钠生理盐水混悬液50μg/100 g灌胃,高剂量左甲状腺素钠组给予左甲状腺素钠生理盐水混悬液150μg/100 g灌胃,对照组给予等剂量的生理盐水灌胃,均1次/d。确定甲亢后,雌雄合笼,受孕后继续灌胃至分娩。取每组中出生21 d、60 d的雄性仔鼠各10只,眼眶取血检测甲状腺功能;取每组中出生当天及出生21 d、60 d雌鼠所产雄性仔鼠各10只,采用Western blot技术检测仔鼠肝脏组织中Caspase-3和Bcl-2蛋白表达情况。结果低、高剂量左甲状腺素钠组仔鼠出生21 d的血清游离三碘甲状腺原氨酸（FT₃）、游离甲状腺素（FT₄）水平均明显高于对照组（P均<0.05）,促甲状腺激素（TSH）水平均明显低于对照组（P均<0.05）;高剂量左甲状腺素钠组血清FT₃、FT₄水平均明显高于低剂量左甲状腺素钠组（P均<0.05）,TSH水平明显低于低剂量左甲状腺素钠组（P<0.05）。与对照组和低剂量左甲状腺素钠组比较,高剂量左甲状腺素钠组仔鼠出生60 d的血清FT₃、FT₄水平均更高（P均<0.05）,TSH水平均更低（P均<0.05）,低剂量左甲状腺素钠组各指标和对照组比较差异均无统计学意义（P均>0.05）。低剂量左甲状腺素钠组仔鼠出生21 d的Caspase-3蛋白相对表达量明显高于对照组（P<0.05）,Bcl-2蛋白相对表达量明显低于对照组（P<0.05）;高剂量左甲状腺素钠组仔鼠出生当天、21 d、60 d的Caspase-3蛋白相对表达量均明显高于同期对照组和低剂量左甲状腺素钠组（P均<0.05）,Bcl-2蛋白相对表达量均明显低于同期对照组和低剂量左甲状腺素钠组（P均<0.05）。结论甲亢母鼠如不治疗可以导致仔鼠甲状腺功能异常及肝脏组织中Caspase-3表达上调、Bcl-2表达下调,引起肝组织细胞凋亡,且重度甲亢母鼠对仔鼠甲状腺功能、肝脏的影响较为严重,这种影响随着后代的生长发育不能有效改善。更多还原

【Abstract】 Objective It is to observe the effect of maternal hyperthyroidism on the expression of Caspase-3 and Bcl-2 in the liver of rat offspring. Methods Thirty six female SD rats were randomly divided into control group, low-dose levothyroxine sodium group and high-dose levothyroxine sodium group, 12 rats in each group.The low-dose levothyroxine sodium group was intragastrically administered levothyroxine sodium normal saline suspension 50 μg/100 g, the high-dose levothyroxine sodium group was intragastrically administered levothyroxine sodium normal saline suspension 150 μg/100 g, and the control group was given equal dose of normal saline by gavage, all once a day. After hyperthyroidism was determined, the male and female were mated and gavage was continued after conception until delivery. 10 male litters on the day of birth, postnatal day 21 and 60 were collected from each group, their blood samples were taken to detect thyroid function; 10 female litters on the postnatal day 21 and 60 were collected from each group to detect the expression of Caspase-3 and Bcl-2 proteins in liver tissues by Western blot. Results The serum levels of free triiodothyronine（FT₃） and free thyroxine（FT₄） of the offsprings in the low and high dose levothyroxine sodium groups were significantly higher than those in the control group at 21 d after birth（P<0.05）, and the level of thyroid stimulating hormone（TSH） was significantly lower than that in the control group（P<0.05）. The serum FT₃ and FT₄ levels in the high-dose levothyroxine sodium group were significantly higher than those in the low-dose levothyroxine sodium group（P<0.05）, and the TSH level was significantly lower than that in the low-dose levothyroxine sodium group（P<0.05）. Compared with the control group and the low-dose levothyroxine sodium group, the serum FT₃ and FT₄ levels at 60 d after birth in the high-dose levothyroxine sodium group were higher（P<0.05）, and the TSH level was lower（P<0.05）, there was no statistical significance in the indexes between the low-dose levothyroxine sodium group and the control group（P>0.05）. The relative expression level of Caspase-3 protein in the low-dose levothyroxine sodium group was significantly higher than that in the control group at 21 days after birth（P<0.05）, and Bcl-2 protein in the low-dose levothyroxine sodium group was significantly lower than that in the control group. The relative expression of Caspase-3 protein in the high-dose levothyroxine sodium group was significantly higher than that in the control group and the low-dose levothyroxine sodium group on day 21 and day 60 of birth（P<0.05）, and the relative expression of Bcl-2 protein in the high-dose levothyroxine sodium group was significantly lower than that in the control group and the low-dose Levothyroxine sodium group（P<0.05）. Conclusion Untreatment hyperthyroidism of pregnancy rats could induce thyroid dysfunction and up-regulation of Caspase-3 expression and down-regulation of Bcl-2 expression in offspring rats, resulting in liver apoptosis. In addition, thyroid function and liver of offspring rats could be seriously affected by maternal rats with severe hyperthyroidism, which cannot be effectively improved with the growth and development of offspring.更多还原