先天性心脏病患儿母体孕期锌代谢及其相关调节子金属硫蛋白-1和锌转运蛋白-1的变化研究

摘要

Objective To investigate maternal zinc metabolism and the changes of zinc-related factors as metallothionein-1 (MT1) and zinc transporter-1 (ZnT1) in certain types of congenital heart diseases (CHD).Methods Fifteen infants with interventricular septal defect,12 infants with atrial septal defect and 7 infants with tetralogy of Fallot,together with their mothers were enrolled,and normal infants and their mothers were enrolled by a ratio of 1 ∶ 1 with the above three types of CHD diseases.General conditions of the mothers,along with their diets and zinc-containing drug supplementation during the pregnancy,were surveyed.Maternal blood zinc levels and serum alkaline phosphatase activities at gestation week 32 and delivery or induced abortion,and the protein and mRNA expressions of MT1 and ZnT1 in maternal serum and placental tissue at delivery or induced abortion were assayed.Results The general conditions were comparable between the CHD group and control group.The ratio of the mothers taking more zinc-rich food was significantly lower in the CHD group than in the control group.Circulating zinc levels in interventricular septal defect (73.55±5.79 μmol/L),atrial septal defect (72.66±5.82 μmol/L) and tetralogy of Fallot (68.72±6.72 μmol/L) groups were significantly lower than those in the control groups (82.77± 7.88,84.58 ± 7.55 and 85.66 ± 7.30 μmol/L) at delivery (P all ＜ 0.05).Similar change patterns were seen for serum alkaline phosphatase activities.The relative quantities of serum MT1 and ZnT1 proteins in interventricular septal defect (73.22±36.54 and 68.55± 27.82),atrial septal defect (64.29± 38.26 and 74.55 ± 29.67) and tetralogy of Fallot (67.88± 30.50 and 70.13±29.65) groups were significantly lower than those in their corresponding control groups (166.31±67.43and 97.67±30.22,182.56±71.40 and 111.65±32.70,and 173.81±62.36 and 108.27±28.52,P＜0.01 or P＜0.05).The relative quantities of placental MT1 and ZnT1 proteins and mRNA expressions in interventricular septal defect (protein quantities 0.438±0.096 and 0.384±0.061,mRNA expressions 1.23±0.82 and 0.96±0.39),atrial septal defect (0.427±0.093 and 0.377±0.059,1.17±0.70 and 0.85±0.40) and tetralogy of Fallot (0.414±0.111 and 0.336±0.066,1.31±0.97 and 0.90±0.38) groups were significantly lower than those in their corresponding control groups (protein quantities 0.565±0.083 and 0.541±0.090,mRNA expressions 2.78± 1.06 and 1.67±0.33;protein quantities 0.622±0.136 and 0.493±0.079,mRNA expressions 2.85±0.89 and 1.72±0.38;protein quantities 0.637±0.125 and 0.521±0.089,mRNA expressions 3.21 ± 0.99 and 1.61±0.29;P＜0.01 or P＜0.05).Conclusion Mothers with their fetus of certain types of CHD are found zinc deficiency,and down-regulation of MT1 and ZnT1 expressions in the serum and placenta may involve in the pathogenesis of CHD when maternal zinc deficiency.%目的 观察特定类型先天性心脏病(CHD)患儿的母亲孕期锌代谢状况、锌代谢相关的金属硫蛋白-1 (MT1)和锌转运蛋白-1(ZnT1)的变化,探讨其间的关系.方法 纳入15例室间隔缺损、12例房间隔缺损、7例法洛四联症患儿及其母亲,按1∶1选择相应正常母婴作为对照,调查CHD组和对照组孕产妇的一般情况和孕期锌相关膳食和锌剂补充的情况;分别于孕32周、分娩或引产时检测孕妇血锌水平和碱性磷酸酶(AKP)活性,于分娩或引产时检测孕妇血清和胎盘组织MT1、ZnT1蛋白和mRNA表达变化.结果 CHD组和对照组母亲的一般情况相近,CHD患儿的母亲孕期摄入富锌食品人数的构成比较对照组显著降低.对于孕妇血锌值,室间隔缺损组[(73.55±5.79) μmol/L]、房间隔缺损组[(72.66±5.82) μmol/L]和法洛四联症组[(68.72±6.72) μmol/L]均较各自分娩时对照组[依次为(82.77±7.88)、(84.58±7.55)、(85.66±7.30) μmol/L]显著降低(P均＜0.05);血清AKP活性值有类似的变化.对于孕妇血清MT1和ZnT1的蛋白相对含量,室间隔缺损组(分别为73.22±36.54、68.55±27.82)、房间隔缺损组(64.29±38.26、74.55±29.67)和法洛四联症组(67.88±30.50、70.13±29.65)与各自对照组(依次为166.31±67.43、97.67±30.22、182.56±71.40、111.65±32.70和173.81±62.36、108.27±28.52)比较均显著降低(P＜0.01或P＜0.05).对于孕妇胎盘MT1和ZnT1的蛋白相对含量及mRNA表达水平,室间隔缺损组(分别为蛋白含量0.438±0.096、0.384±0.061,rnRNA表达水平1.23±0.82、0.96±0.39)、房间隔缺损组(0.427±0.093、0.377±0.059,1.17±0.70、0.85±0.40)和法洛四联症组(0.414±0.111、0.336±0.066,1.31±0.97、0.90±0.38)与各自对照组(依次为蛋白含量0.565±0.083、0.541±0.090,mRNA表达水平2.78±1.06、1.67±0.33;蛋白含量0.622±0.136、0.493±0.079,mRNA表达水平2.85±0.89、1.72±0.38;蛋白含量0.637±0.125、0.521±0.089,mRNA表达水平3.21±0.99、1.61±0.29)比较均显著降低(P＜0.01或P＜0.05).结论 胎儿特定类型CHD的母体存在锌缺乏状况,血清及胎盘的MT1和ZnT1表达下调可能参与母体锌缺乏时CHD的发生.