孕期营养不良对子代大鼠胰岛素抵抗的影响

The effects of pregnancy malnutrition on the development of insulin resistance in rat offspring

目的 探讨孕期营养不良大鼠造成子代宫内发育迟缓 (intrauterinegrowthretardation ,IUGR)成年后胰岛素抵抗 (insulinresistance ,IR)的发生 ,以及肿瘤坏死因子α(TNF α)与其胰岛素抵抗发生的关系 ,并寻求较合理的早期营养干预措施。方法 通过母鼠孕期营养不良建立IUGR模型 ,IUGR新生雌鼠 80只随机分为 4组 ,分别给予下述相应饮食饲料喂养母鼠 3周 ,幼鼠母乳喂养 :IUGR模型组 (S/N组 )给予常规饮食 ,IUGR高热能饮食组 (A组 ) ,IUGR高蛋白高热能饮食组 (B组 ) ,IUGR高蛋白等热能饮食组 (C组 )。另以正常母鼠所生正常新生雌鼠 2 0只为正常对照组 (C/N组 ) ,母鼠给予常规饮食喂养至实验结束。各组幼鼠 3周断乳后 ,第 4周起均予常规饮食喂养。各组大鼠在 12周时(成年期 )、4 8周 (老年期 )时分别测定体重、身长、空腹血糖、胰岛素及脂肪组织TNF α浓度 ,计算体重指数 (BMI)、胰岛素敏感指数 (ISI)、胰岛素抵抗指数 (IRI)、β细胞分泌功能 (HBCI)并分析与TNF α的相关性。结果 12周及 4 8周时 ,IUGR模型组与正常对照组比较 ,体重无统计学意义 ,但已出现肥胖趋势 ,BMI升高、胰岛素敏感性下降、TNF α升高 ,TNF α与ISI呈负相关 ,与IRI正相关 ,与HBCI无关 ;IUGRA、B组成年后出现肥胖 ,较IUGR模型组更为严?

Objective To investigate the effects of pregnancy malnutrition on the occurrence of insulin resistance (IR) in rat offspring during adult stage and to find out the relationship between TNF αand IR; and to find out a reasonable early nutritional intervention measure for the porevention of IR, through giving different diets to offspring Methods An IUGR model was built by maternal nutrition restriction 80 newborn IUGR female pups were randomly divided into 4 groups,the mother rats were given the following diet respectively for 3 weeks after delivery,pups were fed by mother milk: (1) The IUGR (intrauterine growth retardation) rat model was used and the animals were divided into: IUGR control group (group S/N) fed with normal diet, (2) IUGR high caloric diet group (group A), (3) IUGR high protein and high caloric diet group (group B) and (4) IUGR high protein isocaloric diet group (group C) Each group had 20 pups and another 20 normal female pups were fed with normal diet as the normal control group (group C/N) All pups were weaned at the 4 th week of age and fed with normal diet till the end of the experiment At the 12 th week (adulthood) and 48 th week (senility) of life, body weight and length, the fasting blood glucose, insulin concentration, TNF α of adipose tissue and body weight were measured Body mass index (BMI), ISI (insulin sensitive index), IRI(insulin resistant index) and HBCI(βcell insulin excretion index) and their correlation to TNF α were calculated Results At 12 th week and 48 th week of life, the insulin sensitivity of IUGR model group was significantly lower than group C/N, although there was no significant difference of body weight between these two groups TNF α was negatively correlated with ISI, positively correlated with IRI and no relation to HBCI Group A and B was fatter and developed more severe IR There were no significant differences in ISI, IRI, HBCI and TNF α between group C and group C/N Conclusions IUGR offspring of pregnancy malnutrition mother rats showed IR at the age of 12 th week TNF α was closely related to the occurrence of IR in IUGR pups IUGR pups fed with high caloric diet or high protein and caloric diet at the early postnatal period amplified the metabolic abnormality The high protein isocaloric diet is effective early nutritional intervention measure for the prevention of occurrence of IR at adulthood