孕鼠营养异常对子鼠成年后激素抵抗影响的实验研究

目的 探讨孕鼠营养异常对子鼠成年后胰岛素、瘦素抵抗的影响。方法 36只孕鼠随机分成低蛋白组（低蛋白饲料喂养）、高营养组（高营养饲料喂养）及正常营养组（普通饲料喂养）,每组12只,各组孕鼠均足月自然分娩。正常营养组子鼠为正常体重组,低蛋白组子鼠体重小于孕龄（SGA）为SGA组（体重小于正常体重组子鼠平均体重2s以下）,高营养组子鼠体重大于孕龄（LGA）为LGA组（体重高于正常营养组子鼠平均体重2s以上）,每组子鼠36只。于子鼠出生后4周、12周龄时采用酶联免疫吸附试验测定其胰岛素、瘦素水平及胰岛素敏感指数（ISI）。结果 （1）低蛋白组子鼠体重明显低于正常体重组（P〈0．01）,69％的子鼠为SGA。高营养组子鼠体重明显高于正常体重组（P〈0．01）,38％的子鼠为LGA。（2）子鼠出生4周时,SGA组子鼠与正常体重组比较,体重已无显著差异,肾脏周围脂肪重量（FW）、Fw与体重（BW）比值分别为（0．36±0．14）g．6．5±0．3,显著高于正常体重组的（0．19±0．13）g,3．4±0．3（P〈0．01,P〈0．05）;LGA组子鼠FW／BW比值与正常体重组比较,差异无统计学意义（P〉0．05）。子鼠出生12周时,SGA组子鼠体重为（222±19）g,LGA组子鼠体重为（257±24）g,均明显高于正常体重组的（215±25）g（P〈0．05,P〈0．01）。SGA组子鼠FW／BW比值为10．5±5．1,LGA组子鼠为11．8±3．6,均明显高于正常体重组的7．2±3．6（P〈0．01）。（3）SGA组子鼠在出生4周时,胰岛素、瘦素水平分别为（5．5±0．9）μg/L、（6．1±0．7）μg／L,ISI为3．4±0．3,与正常体重组比较,差异有统计学意义（P〈0．05）;出生12周时,胰岛素、瘦素水平及ISI的变化与正常体重组比较,差异有统计学意义（P〈0．01）。LGA组子鼠在出生4周时,胰岛素、瘦素水平及ISI分别为（4．0±1．0）μg／L、（5．0±0．3）μg／L及4．1±0．5,与正常体重组比较,差异无统计学意义（P〉0．05）;出生12周时的胰岛素、瘦素水平及ISI与正常体重组比较,差异有统计学意义（P〈0．01）。结论 孕鼠营养异常将导致子鼠出生体重异常,体重异常子鼠在成年后可发生腹型肥胖以及胰岛素、瘦素抵抗。

Effects of abnormal nutritional supply during pregnancy on adult hormone resistance in rats

OBJECTIVE: To discuss the effects of abnormal nutritional supply during pregnancy on the adult insulin and leptin resistance in rats. METHODS: We established the pregnant rat models given either low protein or high nutrition diet, and normal diet group served as control. There were 12 pregnant rats in each group. After vaginal delivery, the pups birth weight were measured. The randomly selected small for gestational age (SGA) from low protein diet group, large for gestational age (LGA) pups from high nutrition diet group and normal birth weight pups from control group were studied at both 4 weeks and 12 weeks after being born. Each group contained 36 rats. The insulin and leptin level were measured by the method of ELISA, and insulin sensitive index were calculated respectively. RESULTS: The pups of mothers served with low protein showed obviously lower birth weight than those mothers with normal diet (P < 0.01), 69% pups were SGA. While pups of mothers with high nutrition diet showed obviously higher birth weight than those mothers with normal diet (P < 0.01), 38% were LGA. The body weight of rats in SGA group was similar with those in control group at 4-week-age (P > 0.05), while the weight of fat around kidney, the ratio of fat and body weight (FW/BW) were (0.36 +/- 0.14) g, 6.5 +/- 0.3, which were higher than those of control (0.19 +/- 0.13) g, 3.4 +/- 0.3 (P < 0.01, P < 0.05). FW/BW in LGA group showed no obvious difference from that of control. At 12-week-age, the body weight of SGA was (222 +/- 19) g, that of LGA was (257 +/- 24) g, both of them significantly higher than that of control (215 +/- 25) g (P < 0.05, P < 0.01). FW/BW in SGA was 10.5 +/- 5.1, in LGA it was 11.8 +/- 3.6, which were significantly higher than that of control, 7.2 +/- 3.6 (P < 0.01). The higher insulin (5.5 +/- 0.9) microg/L, leptin (6.1 +/- 0.7) microg/L level and lower ISI (3.4 +/- 0.3) were obvious at 4-week-age (all P < 0.05) in SGA group but not in LGA group. At 12-week-age, all of them in the two groups were significantly different compared with those in control (all P < 0.01). CONCLUSIONS: Abnormal nutritional supply during pregnancy can lead to abnormal birth weight. Both low birth weight and high birth weight pups showed obesity with different characteristics and insulin, leptin resistance during adult period.