中文摘要
营养缺乏造成的生长抑制在营养恢复后出现快速生长现象称为追赶生长。我们经过研究发现：1.给予6周限食后开放饮食的追赶大鼠模型GH、leptin分泌水平有显著变化,血清中的总胆固醇，游离脂肪酸逐渐升高与对照组有显著性差异，可能与共同参与了脂肪沉积、胰岛素抵抗状态的形成以及糖代谢障碍。2.高葡萄糖钳夹实验结果显示，追赶生长组糖负荷后一相胰岛素分泌显著低于对照组，证明追赶组大鼠早期已出现beta细胞功能损伤；同时胰腺的免疫组化结果显示追赶组胰岛染色面积比率及胰岛素平均光密度值较对照组显著降低，同时伴有胰岛TNUEL凋亡检测的增高及抗凋亡因子Bcl-2表达的减少，提示追赶生长引起beta细胞的早期凋亡。3.胰升血糖素样肽-1（Pdx-1）是调节胰腺成熟和胰岛素分泌的重要转录因子，追赶生长组pdx-1的表达较对照组显著下降；在对胰岛染色质免疫沉淀的研究发现，追赶生长组的H3K4me3的富集程度较对照组明显降低，而该信号是染色质处于开放状态的标志；相反，H3K9me2的富集程度较对照组显著提高，该指标在常染色质是抑制性信号；此外，追赶生长组H3乙酰化程度较对照组下降，而去乙酰化往往参与染色质的抑制。
英文摘要
Growth suppression caused by deficiency of nourishment displays rapid growth after nourishment recovery known as catch-up growth. We discover several aspects through research as follows: 1.We construct catch-up growth rat model by restoration of normal diet followed by 6 weeks diet restriction. Growth hormone,leptin,total cholesterol and total glycerol in blood serum of catch-up growth is obviously increased compared to normal diet.These may anticipate in fat deposition,insulin resistance and glucose metabolism dysfunction. 2.Results of Hyperglycemia clamp displays that there is no difference in the fasting glucose and insulin between the two groups and the 1st phase insulin secretion declined in the catch-up growth group,proving that beta cells have already injured at early stage of catch-up growth. Meanwhile, Insulin area and average photodensity in histochemistry is critically shrunk in catch-up growth group, accompanying with TUNEL apoptosis increase and anti -apoptosis factor Bcl-2 decline. These facts indicate early-stage catch-up growth have already induced beta-cell early apoptosis. 3.Pdx-1 is a key factor in regulating pancreas maturation and insulin secretion . Pdx-1 expression declines in catch-up growth; besides, in ChromatinImmunoprecipitation H3K4me3 enrichment is declined in catch-up growth,which is signal of chromatin activation;on the contrary, one signal of euchromatin suppression H3K9me2 is evidently decreased.Histone acetylation commonly anticipate in chromatin suppression,and we find that H3 acetylation in catch-up growth is critically declined compared to normal group.
结题摘要
营养缺乏造成的生长抑制在营养恢复后出现快速生长现象称为追赶生长。我们经过研究发现：1.给予6周限食后开放饮食的追赶大鼠模型GH、leptin分泌水平有显著变化,血清中的总胆固醇，游离脂肪酸逐渐升高与对照组有显著性差异，可能与共同参与了脂肪沉积、胰岛素抵抗状态的形成以及糖代谢障碍。2.高葡萄糖钳夹实验结果显示，追赶生长组糖负荷后一相胰岛素分泌显著低于对照组，证明追赶组大鼠早期已出现beta细胞功能损伤；同时胰腺的免疫组化结果显示追赶组胰岛染色面积比率及胰岛素平均光密度值较对照组显著降低，同时伴有胰岛TNUEL凋亡检测的增高及抗凋亡因子Bcl-2表达的减少，提示追赶生长引起beta细胞的早期凋亡。3.胰升血糖素样肽-1（Pdx-1）是调节胰腺成熟和胰岛素分泌的重要转录因子，追赶生长组pdx-1的表达较对照组显著下降；在对胰岛染色质免疫沉淀的研究发现，追赶生长组的H3K4me3的富集程度较对照组明显降低，而该信号是染色质处于开放状态的标志；相反，H3K9me2的富集程度较对照组显著提高，该指标在常染色质是抑制性信号；此外，追赶生长组H3乙酰化程度较对照组下降，而去乙酰化往往参与染色质的抑制。