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[摘要]
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(0.25 mg·kg-1·d-1)、rhGH(0.25 mg·kg-1·d-1)、PEG-rhGH(1.4 mg·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β细胞分泌能力下降,对胰岛分泌蛋白的表达无明显影响。
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[Abstract]
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-1·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 group had 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 β cell secretory capacity are not observed, and no significant effects of PEG-rhGH on secretion function of pancreas islet in hypophysectomized rats are observed.
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