聚乙二醇重组人生长激素注射液对去垂体大鼠模拟成人生长激素缺乏症的实验研究

Effect of PEG-rhGH injection on adult growth hormone deficiency in hypophysectomized rats

目的：利用大鼠去垂体模型模拟成人生长激素缺乏症的代谢紊乱、骨质疏松、认知障碍等临床症状,观察聚乙二醇重组人生长激素注射液（polyethylene glycol-recombinant human growth hormone,PEG-rhGH）的作用,为临床评价提供实验依据。方法：4周龄SD大鼠,手术去除垂体,恢复3周后,将筛选合格的去垂体大鼠按体重均匀随机分组,每组10只,大鼠在第8-11周内颈部皮下给药,阳性药组给予短效制剂重组人生长激素（rhGH）注射液（每周0.90 mg·kg^-1）,每日1次,连续22 d;PEG-rhGH低、中、高剂量组分别给予（每周0.15,0.45,1.35 mg·kg^-1）,每周给药1次,连续4次;另外设有假手术组和模型组。末次给药后次日（d23）检测各指标。结果：与模型组相比,PEG-rhGH各剂量组大鼠体重增重显著升高（P〈0.01）,有量效关系;避暗回避实验中认知能力提高;大鼠骨矿含量显著升高（P〈0.01）;血清胰岛素样生长因子-1（insulinlike growth factors,IGF-1）、骨钙素（bone glaprotein,BGP）和碱性磷酸酶（alkaline phosphatase,ALP）水平均显著升高（P〈0.01或P〈0.05）;大鼠胫骨病理切片的形态观察与计量分析均显示PEG-rhGH各剂量组骨密度增加。结论：PEG-rhGH（每周0.15-1.35 mg·kg^-1）对去垂体大鼠可明显增加大鼠体重;改善认知功能;增加骨密度,升高IGF-1水平。预示PEG-rhGH对AGHD患者的部分临床症状具有一定的治疗改善作用,可预防和治疗老年痴呆和骨质疏松等症。

Objective： To observe the effect of polyethylene glycol recombinant human growth hormone（ PEG-rhGH） injection on clinical symptoms of metabolic disorders,osteoporosis and cognitive disorders in hypophysectomized（ HYPOX） rats that simulate adult growth hormone deficiency（ AGHD）,for providing experimental basis for clinical evaluation. Methods： In 4 week old rats,hypophysectomization was performed and recovered for3 weeks. HYPOX rats were randomly divided into groups（ 10 rats per group） according to body weight. They were injected with PEG-rhGH（ 0. 15,0. 45,1. 35 mg·kg^- 1·wk^- 1） once weekly for 4 weeks,and rhGH（ 0.90 mg·kg^- 1·wk^- 1） was injected once daily for 22 d from 8th to 11 th weeks as the positive control. Indicators were determined on the next day after the last administration（ d 23）. Results： Compared with HYPOX control group,thebody weight and weight gain were significantly increased in each PEG-rhGH dose group（ P〈0. 01） in a dose-dependent manner. Cognitive ability in a dark avoidance experiment,bone mineral content,serum level of insulinlike growth factor-1（ IGF-1）,osteocalcin（ bone glaprotein,BGP） and alkaline phosphatase（ ALP） levels,and the bone mineral density were improved significantly（ P〈0. 01 or P〈0. 05） in PEG-rhGH-treated HYPOX rats.Conclusion： PEG-rhGH effectively improves the body weight gain,cognitive function,BGP and serum IGF-1 levels in HYPOX rats. Thus,PEG-rhGH can partly improve the clinical symptoms of AGHD,and may prevent and treat senile dementia and osteoporosis.