孕期、哺乳期高碘摄入对子代雄鼠脂代谢的影响

Effects of excessive iodide intake during pregnancy and lactation on lipid metabolism in offspring male rats

目的探讨孕期和哺乳期高碘摄入对子代雄鼠脂代谢的影响。方法将48只6周龄Wistar大鼠(雌雄各半),适应性喂养1周后,按雌雄1∶1合笼;采用随机数字表法根据体重(220~240 g)将孕鼠分为2组进行干预。(1)孕期、哺乳期10倍高碘(10 HI)摄入至子代出生后(PN)21 d(PN21):将孕鼠分为适碘组(NI组,饮用去离子水),10 HI组(饮用碘含量为2250μg/L的碘化钾溶液);母乳喂养子代大鼠至PN21,以子代雄鼠为研究对象,每组6只。(2)孕期、哺乳期100倍高碘(100 HI)摄入至子代PN120:将孕鼠分为NI组(饮用去离子水),100 HI组(饮用碘含量为24750μg/L的碘化钾溶液);母乳喂养子代大鼠至PN21,此后子代继续饮用与母代相同碘含量的碘化钾溶液至PN120,以子代雄鼠为研究对象,每组6只。采用酶联免疫吸附试验(ELISA)法测定血清游离三碘甲状腺原氨酸(FT_(3))、游离甲状腺素(FT_(4))、促甲状腺激素(TSH)以及血清和肝组织匀浆中低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、总胆固醇(TC)水平;实时荧光定量PCR检测肝组织中低密度脂蛋白受体(LDLR)、胆固醇7α-羟化酶(CYP7A)、固醇调节元件结合蛋白(SREBP)-1c、苹果酸酶(ME)、甲状腺激素受体β(TRβ)mRNA的表达水平。结果(1)孕期、哺乳期10 HI摄入至PN21对子代雄鼠的影响:NI和10 HI组子代雄鼠血清FT_(3)[(7.53±0.74)、(8.88±0.99)pmol/L],FT_(4)[(5.58±0.56)、(7.68±0.30)pmol/L],TSH水平[(16.69±1.05)、(14.49±0.16)ng/ml]比较,差异均有统计学意义(t=-2.91、-8.76、3.59,P均<0.05)。10 HI组子代雄鼠血清和肝脏LDL-C、TG、TC水平均明显低于NI组(t=3.28、8.71、3.44,3.70、3.49、2.74,P均<0.05)。NI和10 HI组子代雄鼠肝脏LDLR、ME、SREBP-1c mRNA水平比较,差异均有统计学意义(t=-3.50、-3.92、5.58,P均<0.05);其中,10 HI组LDLR、ME mRNA水平均高于NI组,而SREBP-1c mRNA水平低于NI组。两组间CYP7A、TRβmRNA水平比较,差异均无统计学意义(t=-2.44、3.20,P均>0.05)。(2)孕期、哺乳期100 HI摄入至PN120对子代雄鼠的影响:NI和100 HI组子代雄鼠血清FT_(3)、FT_(4)、TSH水平比较,差异均有统计学意义(t=-4.39、-3.19、4.72,P均<0.05);其中,100 HI组血清FT_(3)、FT_(4)水平均低于NI组,TSH水平高于NI组。与NI组比较,100 HI组子代雄鼠血清、肝脏LDL-C、TG、TC水平均明显较高,差异均有统计学意义(t=4.49、12.85、16.62,4.35、11.04、16.01,P均<0.05)。NI和100 HI组子代雄鼠肝脏CYP7A、LDLR、ME、SREBP-1c、TRβmRNA水平比较,差异均有统计学意义(t=26.40、54.85、-10.98、10.50、32.52,P均<0.05);其中,100 HI组CYP7A、LDLR、ME、TRβmRNA水平均低于NI组,而SREBP-1c mRNA水平高于NI组。结论孕期、哺乳期10 HI高碘摄入至子代雄鼠PN21出现甲状腺功能亢进的血清学改变,血脂和肝脂水平下降,肝脏LDLR、ME mRNA水平上调,SREBP-1c mRNA水平下调;而孕期、哺乳期100 HI高碘摄入至子代雄鼠PN120出现甲状腺功能减退的血清学改变,血脂和肝脂水平上升,肝脏CYP7A、LDLR、ME mRNA水平下调,SREBP-1c mRNA水平上调。

Objective To study the impact of excessive iodide intake during pregnancy and lactation on lipid metabolism in offspring male rats.Methods Forty-eight six-week-old Wistar rats(half male and half female)were fed adaptively for one week.The cage was closed according to the ratio of male and female 1∶1.The pregnant rats were divided into two groups according to their weight(220-240 g)by random number table.(1)10 times high iodine(10 HI)intake during pregnancy and lactation until the postnatal day 21(PN21)of their offspring:pregnant rats were divided into normal iodine group(NI group,drinking deionized water),10 HI group(drinking potassium iodide solution with iodine content of 2250μg/L).Breast milk was used to feed the offspring rats to PN21,and the offspring male rats were taken as the research subjects,with 6 rats in each group.(2)100 times high iodine(100 HI)intake during pregnancy and lactation to the offspring postnatal day 120(PN120):pregnant rats were divided into NI group(drinking deionized water)and 100 HI group(drinking potassium iodide solution with iodine content of 24750μg/L).After feeding the offspring rats with breast milk until PN21,the offspring were continued to drink potassium iodide solution with the same iodine content as the mother's to PN120.The offspring male rats were taken as the research subjects,with 6 rats in each group.The levels of free triiodothyronine(FT_(3)),free thyroxine(FT_(4)),thyrotropin(TSH)in serum,low-density lipoprotein cholesterol(LDL-C),triglyceride(TG)and total cholesterol(TC)in serum and liver tissue homogenates were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA expression of cholesterol 7α-hydroxylase(CYP7A),low-density lipoprotein receptors(LDLR),sterol regulatory element-binding protein(SREBP)-1c,malic enzyme(ME)and thyroid hormone receptorβ(TRβ)in the liver tissue were measured by real-time quantitative PCR.Results(1)Effects of 10 HI intake during pregnancy and lactation on PN21 offspring male rats:compared with NI and 10 HI groups,the serum FT_(3)[(7.53±0.74),(8.88±0.99)pmol/L],FT_(4)[(5.58±0.56),(7.68±0.30)pmol/L],TSH levels[(16.69±1.05),(14.49±0.16)ng/ml]of offspring male rats were statistically significant(t=-2.91,-8.76,3.59,P<0.05).The levels of LDL-C,TG,TC in serum and liver of offspring male rats of 10 HI group were significantly lower than those of NI group(t=3.28,8.71,3.44,3.70,3.49,2.74,P<0.05).The differences of mRNA expression levels of LDLR,ME,SREBP-1c in the liver of PN21 offspring male rats of 10 HI and NI groups were statistically significant(t=-3.50,-3.92,5.58,P<0.05).Among them,the levels of LDLR and ME in 10 HI group were higher than those in NI group,while the level of SREBP-1c in 10 HI group was lower than that in NI group.There no significant difference in CYP7A and TRβmRNA levels between the two groups(t=-2.44,3.20,P>0.05).(2)Effects of 100 HI intake during pregnancy and lactation on PN120 offspring male rats:there were significant differences in serum FT_(3),FT_(4) and TSH levels of offspring male rats between 100 HI and NI groups(t=-4.39,-3.19,4.72,P<0.05).The levels of serum FT_(3) and FT_(4) in 100 HI group were lower than those in NI group,and the level of TSH in 100 HI group was higher than that in NI group(P<0.05).Compared with NI group,the serum and liver LDL-C,TG and TC levels in the offspring male rats of 100 HI group were significantly higher(t=4.49,12.85,16.62,4.35,11.04,16.01,P<0.05).The differences of CYP7A,LDLR,ME,TRβand SREBP-1c mRNA levels in liver of PN120 offspring male rats of 100 HI and NI groups were statistically significant(t=26.40,54.85,-10.98,32.52,10.50,P<0.05).Among them,the CYP7A,LDLR,ME and TRβmRNA levels in 100 HI group were lower than those of NI group,while the SREBP-1c mRNA level was higher than that of NI group(P<0.05).Conclusions 10 HI intake during pregnancy and lactation to the offspring male rats PN21 showed the serological changes of hyperthyroidism,the levels of blood lipids and liver lipids decreased,the levels of LDLR and ME mRNA increased,and SREBP-1c mRNA decreased in liver.However,100 HI intake during pregnancy and lactation to the offspring male rats PN120 showed serological changes of hypothyroidism,the levels of blood lipids and liver lipids increased,the levels of CYP7A,LDLR,ME mRNA decreased,and SREBP-1c mRNA increased in liver.