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目的观察哺乳期过度喂养大鼠断乳后胃组织脑肠肽生长激素释放肽(Ghrelin)表达和循环中瘦素(Leptin)水平的变化,探讨早期过度喂养导致成年期代谢综合征的病理生理机制。方法应用SD大鼠模型,雄仔出生后分为正常喂养组(NF组,每窝10只)和哺乳期过度喂养组(OF组,每窝3只)。出生3周断乳,均给予正常饮食。ELISA法及放射免疫分析法分别测定其血清Leptin、Ghrelin及胰岛素水平,实时定量PCR及免疫组织化学测定其胃组织Ghrelin mRNA和蛋白表达水平。结果 OF组大鼠从出生第2周起体质量持续显著高于NF组(P<0.05),并在16周时出现糖耐量受损,胰岛素水平显著增加(P<0.05)。NF组和OF组血清Leptin水平自青春期迅速增加,第4周起,OF组Leptin水平显著高于NF组(F=7.94,P<0.05),血清Ghrelin在各时间点上均无组间差异(Pa>0.05)。NF组和OF组胃组织Ghrelin mRNA的表达均随年龄逐渐增加,在8周时达高峰(P<0.05),但2组间在各个时间点上差异均无统计学意义(Pa>0.05)。免疫组织化学显示Ghrelin阳性细胞面积的变化趋势同mRNA表达基本一致。结论大鼠哺乳期过度喂养可导致其成年期肥胖和胰岛素抵抗。哺乳期过度喂养对大鼠胃组织Ghrelin表达和分泌无明显影响,但血清Leptin水平持续升高,长期食欲调控的抵抗和代谢失衡可能参与成年期肥胖和代谢紊乱的发生。
Objective To observe the changes of ghrelin expression and circulating leptin level in weaned rats after weaning, and to explore the pathophysiological mechanism of early overfeeding leading to metabolic syndrome in adulthood . Methods Sprague-Dawley rats were divided into normal group (NF group, 10 per litter) and overfeeding group (OF group, 3 per litter). 3 weeks weaned weaning, are given a normal diet. Serum Leptin, Ghrelin and insulin levels were measured by ELISA and radioimmunoassay. Ghrelin mRNA and protein levels were determined by real-time PCR and immunohistochemistry. Results The body weight of OF rats in the two groups was significantly higher than that in NF group from the second week of birth (P <0.05). At the 16th week, the impaired glucose tolerance and insulin levels were significantly increased (P <0.05). Serum Leptin level increased rapidly from puberty in NF group and OF group, and Leptin level in OF group was significantly higher than that in NF group from the 4th week (F = 7.94, P <0.05). Serum Ghrelin showed no difference between groups at each time point Pa> 0.05). The expression of Ghrelin mRNA in both NF group and OF group increased with age and peaked at 8 weeks (P <0.05), but there was no significant difference between the two groups at each time point (P> 0.05). Immunohistochemistry showed that the trend of Ghrelin positive cell area was consistent with the mRNA expression. Conclusion Overfeeding during lactation can lead to obesity and insulin resistance in adulthood. Overexpression during lactation had no significant effect on Ghrelin expression and secretion in rat gastric tissue, but serum Leptin levels continued to increase, and long-term loss of appetite control and metabolic imbalance may be involved in obesity and metabolic disorders during adulthood.