小鼠妊娠期甲状腺功能减退诱导雌性子代生命早期脂质代谢紊乱

Hypothyroidism during pregnancy in mice induces lipid dysregulation in female offspring′s early life

目的通过构建小鼠妊娠期甲状腺功能减退模型,评估对雌性子代生命早期脂质代谢的影响。方法将雌性小鼠(C57BL/6J)随机分为正常对照组(NC0)、甲状腺功能减退合并妊娠组(PH0)、妊娠伴发甲状腺功能减退组(GH0)。首先对PH0组给予含0.15%丙基硫氧嘧啶饲料喂养28 d,NC0组和GH0组则给予正常饲料喂养。确认造模成功后进行合笼,妊娠期间,GH0组和PH0组雌鼠给予含0.15%丙基硫氧嘧啶饲料,NC0组则给予正常饲料喂养。分娩后,在3周龄时检测各组雌性子代血清游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)和血清总胆固醇(TC)、三酰甘油(TG)的水平;HE染色法观察甲状腺、肝脏病理改变;Western blot检测与脂质代谢相关的蛋白水平。结果与NC0组比较,PH0组与GH0组雌性子代的血清FT3、FT4水平降低,血清TSH水平升高,血清TC水平和肝脏TC、TG水平升高,肝脏存在脂质沉积的现象,肝脏中与脂质代谢相关蛋白HMGCR、FAS、CD36的表达水平升高,CPT1A、LDL-R的表达发生了下调。结论小鼠妊娠期甲状腺功能减退能够导致雌性子代生命早期脂质代谢紊乱。

Objective To evaluate the effect of maternal hypothyroidism on lipid metabolism in the early life of female offspring by constructing a murine model during pregnancy.Methods Female mice C57BL/6J were randomly divided into normal control group(NC0),hypothyroidism complicated with pregnancy group(PH0)and pregnancy complicated with hypothyroidism group(GH0).Firstly,PH0 group was given 0.15%propylthiouracil diet for 28 days,while NC0 and GH0 groups were given normal diet.After the successful modeling of PH0 was confirmed,female mice in GH0 and PH0 groups were given 0.15%propylthiouracil diet during pregnancy,and NC0 group was still given normal diet.After delivery,the levels of free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH)and total cholesterol(TC),triglyceride(TG)in each group were detected at 3 weeks of age for female offspring.The pathological changes of thyroid and liver were observed by HE staining.Western blot detected the levels of proteins associated with lipid metabolism.Results Compared with the NC0 group,the levels of serum FT3 and FT4 decreased,the levels of serum TSH,serum TC,hepatic TC and TG increased in the female offspring of the PH0 and GH0 groups,and lipid deposition was observed in their livers.The expression levels of HMGCR,FAS and CD36 related to lipid metabolism in livers increased,while the expressions of CPT1A and LDL-R were down-regulated.Conclusion Hypothyroidism during pregnancy may lead to the disturbance of lipid metabolism in the early life of female offspring mice.