Effect of a high protein and high caloric diet on the onset of puberty and insulin growth factor-1 (IGF-1) axis in female rats with malnutrition induced by endotoxemia
ZHANG Miao, DU Min-Lian, MA Hua-Mei, LAI Feng
Department of Pediatrics, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510089, China
摘要 目的 慢性营养不良恢复期可能会发生青春期发动提前，本研究探讨恢复期营养干预对内毒素血症致致营养不良幼年雌性大鼠青春发动及IGF-1轴的影响。 方法 体重匹配的同龄同窝幼年雌鼠，随机分至对照组(C组)及LPS处理组(L组)(均n=8)。实验1，L1组于生后7-13 d隔日注射内毒素脂多糖(LPS)共4次，模拟反复感染；实验2，L2组于生后14～20 d同样给予LPS。对照组与相应L组同时注射 0.1 ml PBS，并予正常饮食。恢复期L1及L2组予高蛋白高热卡饲料喂养至体重赶上相应的C1及C2组。观察雌鼠的阴道口开放(VO)、第1个动情(E)日龄及动情后期(M期)卵巢黄体的形成；血浆TNFα、IGF-1及IGFBP-3水平的变化。 结果 ① L1组VO及E日龄均与C1组相似(33.13±2.90 d vs 33.50±2.67 d；37.13±2.59 d vs 35.88±1.81 d，P>0.05)；两组M期卵巢黄体数无统计学差异(3.75±1.67 vs 3.13±1.13，P>0.05)。② L1组内毒素血症期末血TNFα水平高于C1组(1.13±0.57 U/ml vs 0.71±0.18 U/ml，P<0.05)；而血IGF-1水平则低于C1组(201.63±28.31 ng/ml vs 250.91±35.07 ng/ml，P<0.05)。恢复早期L1组血IGF1水平回升并高于C1组(289.20±39.07ng/ml vs 249.88±33.50 ng/ml，P<0.05)，且与体重失去相关性(r=-0.447，P>0.05)。③ L2组VO及E日龄，M期卵巢黄体数与C2组相比亦无统计学差异(P>0.05)。 结论 恢复期营养干预有助于内毒素血症后雌鼠获得与正常鼠相似的青春期发动和性成熟；恢复早期血IGF-1水平骤升有助于生长追赶，但不会诱发性早熟。［中国当代儿科杂志，2004, 6(5): 353-359］
Abstract：OBJECTIVE: An early onset of puberty may occur during convalescence from chronic malnutrition in children. This study aims to explore the effect of a high protein and high caloric diet during convalescence on the onset of puberty in female rats with malnutrition induced by recurrent endotoxemia, and to investigate the change of IGF-1 axis during the period. METHODS: This study was done using the randomized paired design and consisted of two experiments with newborn SD rats. Two female rats from the same litter and matched in weight were randomized to a control group (C group) or a lipopolysaccharide (LPS) treated group (L group) (both n=8). In Experiment one, during 7-13 days of age, rats in the L1 group were given 4 intraperitoneal injections of LPS every other day to duplicate recurrent infection. In Experiment two, during 14-20 days of age, rats in the L2 group were given LPS every other day in the same dose as L1 group. Rats in the C groups were given intraperitoneal injections of 0.1 ml PBS at the same time as the corresponding L group and were fed with a regular diet. During convalescence, rats in the L1 and L2 group were given high protein and high caloric diets (containing 30% casein and 10% fat) until their weights caught up with that of the matched rats in the C1 or C2 group. The age of vaginal opening (VO) and first estrus were observed, and the number of corpora lutea of their ovaries during metestrus (M) were examined. The concentrations of plasma IGF-1, IGF binding protein-3 (IGFBP-3) and TNF-α were measured at ages of 14, 17 and 28 days. RESULTS: 1) There were no significant differences between the L1 and C1 groups in the average age of VO and first estrus. The number of corpora lutea were similar in both groups. 2) On the 14 th day of age, the plasma TNF-α concentration of rats in the L1 group was higher than that of the C1 group ( 1.13± 0.57 U/ml vs 0.71± 0.18 U/ml, P< 0.05), and plasma IGF-1 concentration of rats in the L1 group was lower than that of the C1 group ( 201.63± 28.31 ng/ml vs 250.91± 35.07 ng/ml, P< 0.05). At the early stage of convalescence, weight of rats in the L1 group was still lower than that of control rats ( 34.79± 2.74 g vs 39.23± 2.04 g, P< 0.01), but the plasma IGF-I concentration in the L1 group was significantly higher than that of the controls ( 289.20± 39.07 ng/ml vs 249.88± 33.50 ng/ml, P< 0.05). The correlation between the plasma IGF-I concentration and body weight had disappeared (r= -0.447, P> 0.05). 3) In Experiment 2 there was no difference in the puberty onset between the L2 and C2 groups. CONCLUSIONS: Nutrition intervention with a high protein and high calorie diet during convalescence is useful in inducing a normal onset of puberty and sexual maturation in female rats following endotoxemia. An increased level of IGF-1 during early convalescence may be associated with catch-up growth, but not with precocious puberty.
ZHANG Miao,DU Min-Lian,MA Hua-Mei et al. Effect of a high protein and high caloric diet on the onset of puberty and insulin growth factor-1 (IGF-1) axis in female rats with malnutrition induced by endotoxemia[J]. CJCP, 2004, 6(5): 353-360.
