Zhang Zhi Xin, Liu Ying Ke, Pan Hui, Pan Lin, Zhang Qiong, Su Hui Min, Zhao Qiu Ling, Li Hong, He Chun
Department of Pediatric, China-Japan Friendship Hospital, Beijing, China.
Growth Horm IGF Res. 2012 Feb;22(1):30-5. doi: 10.1016/j.ghir.2011.12.002. Epub 2012 Jan 16.
To study the effect of polyethylene glycol recombinant human growth hormone on growth and glucose metabolism in hypophysectomized rats, and compare the effect of treatment between recombinant human growth hormone (rhGH) and polyethylene glycol rhGH (PEG-rhGH).
Hypophysectomy was performed in juvenile rats to build the animal model of GH deficiency. The hypophysectomized animals were randomly assigned into three groups and treated with saline (negative control, n=20), rhGH (n=20) and PEG-rhGH (n=20). A sham operation was performed to set up the normal control (n=20). Body weight, body length and tail length were recorded every 2days for a 14-day treatment and bone growth was measured at the end of therapy. Glucose infusion rate (GIR) determined by euglycemic hyperinsulinemic clamp was used to evaluate insulin sensitivity after GH treatment. We also examined plasma glucose and serum insulin levels
Compared with the negative control, the body weight, body length, tail length and bone growth increased significantly in hypophesectomized rats treated by GH (P<0.01). Although the weight gain in the first 10days was higher in the PEG-rhGH group than in the rhGH group (P<0.05), the growth promoting effect was similar between rhGH and PEG-rhGH (P>0.05). Neither rhGH nor PEG-rhGH impaired glucose tolerance of rats after hypophesectomy. Compared with negative controls, according to decreased serum insulin, reduced insulin expression in pancreatic cells and increased GIR in the clamp, both rhGH and PEG-rhGH groups had improved insulin sensitivity within 14 days (P<0.01). However, with prolonged treatment, the GIR in the rhGH-treated rats decreased significantly (P<0.05); while PEG-rhGH did not interfere with GIR, even after a doubled dose (P>0.05).
PEG-rhGH had the same linear growth promoting efficacy as unmodified rhGH. The short-term GH replacement could improve insulin sensitivity in hypophysectomized rats, especially after PEGylation.
研究聚乙二醇重组人生长激素对垂体切除大鼠生长及糖代谢的影响，并比较重组人生长激素（rhGH）与聚乙二醇重组人生长激素（PEG-rhGH）的治疗效果。
对幼年大鼠进行垂体切除以建立生长激素缺乏动物模型。将垂体切除的动物随机分为三组，分别用生理盐水（阴性对照，n = 20）、rhGH（n = 20）和PEG-rhGH（n = 20）进行治疗。进行假手术以建立正常对照（n = 20）。治疗14天期间每2天记录体重、体长和尾长，并在治疗结束时测量骨生长。通过正常血糖高胰岛素钳夹法测定的葡萄糖输注速率（GIR）用于评估生长激素治疗后的胰岛素敏感性。我们还检测了血浆葡萄糖和血清胰岛素水平。
与阴性对照相比，生长激素治疗的垂体切除大鼠的体重、体长、尾长和骨生长显著增加（P < 0.01）。虽然PEG-rhGH组前10天的体重增加高于rhGH组（P < 0.05），但rhGH与PEG-rhGH之间的促生长作用相似（P > 0.05）。rhGH和PEG-rhGH均未损害垂体切除大鼠的糖耐量。与阴性对照相比，根据血清胰岛素降低、胰腺细胞中胰岛素表达减少以及钳夹试验中GIR增加，rhGH组和PEG-rhGH组在14天内胰岛素敏感性均有所改善（P < 0.01）。然而，随着治疗时间延长，rhGH治疗大鼠的GIR显著降低（P < 0.05）；而PEG-rhGH即使在剂量加倍后也不影响GIR（P > 0.05）。
PEG-rhGH与未修饰的rhGH具有相同的线性促生长疗效。短期生长激素替代可改善垂体切除大鼠的胰岛素敏感性，尤其是聚乙二醇化后。
