聚乙二醇化重组人生长激素对去垂体幼鼠胰岛分泌的影响及其机制

目的观测长效生长激素聚乙二醇化重组人生长激素（PEG-rhGH）是否引起胰岛素抵抗及其与短效生长激素注射用重组人生长激素（rhGH）的差异。方法3周龄SD雄性幼鼠106只，随机取88只进行去垂体手术造模，取成模的幼鼠54只分为模型组、rhGH组、PEG-rhGH组，另18只假手术组为对照组。分别给予生理盐水（0．25mg·kg-1．d-1）、rhGH（0．25mg·kg-1．d-1）、PEG-rhGH（1．4mg·kg-1周-1）处理。4周后进行糖耐量实验和胰岛素释放试验，计算胰岛素曲线面积与葡萄糖曲线面积比值，胰岛素稳态模型（HOMA-IR）；检测血清生长抑素水平；免疫组织化学法检测胰岛胰岛素（INs）、胰高血糖素（GLU）、生长抑素（SS）、胰多肽（PP）。结果PEG-rhGH组HOMA-IR较对照组、模型组低（P〈0．05），与rhGH组比较无差异。AUCI／AUCG值组间比较显示PEG-rhGH组高于rhGH组，但无统计学差异。PEG-rhGH组GLU蛋白表达与模型组表达无差异。PEG-rhGH组INS表达较模型组表达上升（P〈0．05）。PEG-rhGH组SS、PP表达与rhGH无差异。血清SS各组间均无明显差异。结论未观察到PEG-rhGH引起去垂体大鼠胰岛素抵抗和胰岛D细胞分泌能力下降，对胰岛分泌蛋白的表达无明显影响。

Effect of pegylation recombinant human growth hormone on secretion function of pancreas islet in hypophysectomized rats and its mechanism

Objective To observe whether the long-acting growth hormone polyethylene glycol recombinant human growth hormone （PEG-rhGH） causing insulin resistance or not, and the differences with the short-acting growth hormone recombinant human growth hormone （rhGH）. Methods Sprague-Dawley young rats （106 rats） weighing 60 - 80 g were underwent hypophysectomy via parapharyngeal approach, and 18 rats with Sham operation were selected into the control group. Fifty-four qualified rats were randomly divided into the model, rhGH, and PEG-rhGH groups after two weeks, which were administered with saline （0.25 mg·kg ·d-1）, rhGH （0.25 mg·kg-1·d-1）, and PEG-rhGH （1.4 mg·kg-1·week 1）, respectively. After treatment for 4 weeks, glucose tolerance test and insulin release test were performed to calculate area under the curve insulin （AUCI）, area under the curve glucose （AUCG）, and homeostasis model assessment （HOMA-IR）. Serum somatostatin （SS） levels were determined. Immunohistochemistry displayed the insulin （INS）, glucagon （GLU）, SS, and pancreatic polypeptide （PP）. Results Glucose tolerance test and insulin release test indicated that HOMA-IR in PEG-rhGH group declined compared with those in the control and model groups （P 〈 0.05）, and there were no difference between rhGH and PEG-rhGH groups. The value of AUCI/AUCG in PEG-rhGH group was higher than that of rhGH group without significant difference. Protein expression of GLU indicated no difference among PEG-rhGH, control, and model groups. The INS expression in PEG-rhGH group increased compared with the control group （P〈0.05）. SS and PP expression in PEG-rhGH grouphad no difference compared with that in rhGH group, and there was no significant difference of SS in serum among each group. Conclusion Insulin resistance and decreased islet 13 cell secretory capacity are not observed, and no significant effects of PEG-rhGH on secretion function of pancreas islet in hypophysectomized rats are observed.