孕前肥胖和孕期过度增重母鼠哺乳期饮食对子鼠炎性指标及铁相关指标的影响

Effect of lactation diet in rats with pre-pregnancy obesity and excessive gestational weight gain on inflammatory and iron-related indicators in the offspring

目的探究孕前肥胖和孕期过度增重母鼠哺乳期饮食对子鼠离乳后炎性指标及铁相关指标的影响。方法将24只健康的SPF级Wistar雌性大鼠以1∶1比例随机分为孕前肥胖组和孕期过度增重组,根据哺乳期饮食进一步均分为孕前肥胖-哺乳期高脂饮食组(n=6)、孕前肥胖-哺乳期标准饮食组(n=6)、孕期过度增重-哺乳期高脂饮食组(n=6)、孕期过度增重-哺乳期标准饮食组(n=6)。每组随机抽取12只子鼠(雌雄各半),共48只子鼠纳入研究;出生后第21天离乳,离乳后均饲喂标准饲料。哺乳期第0、7、14、21、28、35和42天测量子鼠体重;第28、35和42天(离乳后第7、14和21天)检测血中白细胞介素-6(IL-6)、铁调素(hepcidin)、铁蛋白(ferritin)、血红蛋白(Hgb)、平均血红蛋白量(Mch)和平均红细胞体积(Mcv)。结果与哺乳期高脂饮食组相比,标准饮食可显著降低孕前肥胖和孕期过度增重母鼠子代的体重;显著降低孕前肥胖母鼠子代的IL-6(第28天,152.97 pg/mL vs.105.24 pg/mL;第35天,155.15 pg/mL vs.110.53 pg/mL;第42天,155.4 pg/mL vs.139.02 pg/mL,P均<0.017)和Hepcidin的水平(119.99 ng/mL vs.99.67 ng/mL,P<0.05),升高Mch(22.43 pg vs.23.32 pg,P<0.05)和Mcv的水平(72.71 fL vs.75.71 fL,P<0.05);显著降低孕期过度增重母鼠子代的IL-6水平(第35天,140.21 pg/mL vs.127.57 pg/mL,P<0.017),升高Hgb(出生后第35天,107.25 g/L vs.112.92 g/L,P<0.017)和Mcv的水平(72.90 fL vs.74.34 fL,P<0.05)。此外,哺乳期标准饮食还显著降低了孕前肥胖母鼠子代的Ferritin(50.60 ng/mL vs.42.06 ng/mL,P<0.05)和Hgb(110.53 g/L vs.106.28 g/L,P<0.05)。调整炎性指标IL-6和Hepcidin后,哺乳期饮食对孕前肥胖和孕期过度增重母鼠子代多个铁相关指标的影响不再具有统计学意义。结论孕前肥胖和孕期过度增重母鼠哺乳期标准饮食可降低子鼠炎症反应、升高铁相关指标水平,且炎症反应可能在母鼠哺乳期饮食与子鼠铁相关指标的关联中发挥机制作用。

Objective To investigate the effects of lactation diet in rats with pre-pregnancy obesity and excessive gestational weight gain on inflammatory and iron-related indicators in the offspring.Methods A total of 24 SPF-rated Wistar female rats were randomly divided into pre-pregnancy obesity group(Pre-obe)and excessive gestational weight gain group(GWG)in a 1:1 ratio,and further divided equally into Pre-obe high-fat diet group(n=6),Pre-obe standard diet group(n=6),GWG high-fat diet group(n=6),and GWG standard diet group(n=6)according to lactation diet.A total of 48 offspring rats were included in the study with 12 rats in each group;they were weaned on the 21st day after birth,and all were fed a standard diet after weaning.Body weights were measured on the days 0,7,14,21,28,35 and 42 after birth.Interleukin-6(IL-6),hepcidin,ferritin,hemoglobin(Hgb),mean corpuscular hemoglobin(Mch),and mean corpuscular volume(Mcv)in the serum/whole blood were measured on the days 28,35 and 42 after birth.Results Compared with a high-fat diet during lactation,the standard diet significantly reduced the body weight.Compared with a high-fat diet during lactation,the standard diet significantly reduced the level of IL-6(152.97 pg/mL vs.105.24 pg/mL on day 28;155.15 pg/mL vs.110.53 pg/mL on day 35;155.4 pg/mL vs.139.02 pg/mL on day 42,P<0.017)and Hepcidin(119.99 ng/mL vs.99.67 ng/mL,P<0.05),and increased the level of Mch(22.43 pg vs.23.32 pg,P<0.05)and Mcv(72.71 fL vs.75.71 fL,P<0.05)of the offspring in Pre-obe.Compared with a high-fat diet during lactation,the standard diet significantly reduced the level of IL-6(140.21 pg/mL vs.127.57 pg/mL on day 35,P<0.017),and increased the level of Hgb(107.25 g/L vs.112.92 g/L on day 35,P<0.017)and Mcv(72.90 fL vs.74.34 fL,P<0.05)of the offspring in GWG.In addition,the standard diet during lactation significantly reduced the level of Ferritin(50.60 ng/mL vs.42.06 ng/mL,P<0.05)and Hgb(110.53 g/L vs.106.28 g/L,P<0.05)of the offspring in Pre-obe.After adjusting for inflammatory indicators(IL-6 and Hepcidin),the effect of lactation diet on multiple iron-related indicators of the offspring in Pre-obe and GWG was no longer statistically significant.Conclusion Our results suggest that the standard diet during lactation in rats with pre-pregnancy obesity and excessive weight gain during pregnancy reduces the inflammatory response and increases the levels of iron-related indicators in the offspring,and the inflammatory response may play a mechanistic role in the association between maternal diet during lactation and iron-related indicators in the offspring.