摘要
目的观察司坦唑醇(ST)对注射促性腺激素释放激素类似物(GnRHa)的青春期SD大鼠长骨生长的影响,在生长板水平观察ST是否能促进大鼠长骨的生长/成熟平衡。方法90只雌鼠3周龄末时断乳按随机分组(同窝)设计分7个量效组:5 000μg/100 g、200μg/100 g、100μg/100 g、50μg/100 g、25μg/100 g、溶剂对照组、空白对照组(每组6只),分为8个时效组(每组6只),并开始肌注GnRHa制剂曲普瑞林,每2周1次,共2次,在第2次注射GnRHa3 d(D1)后开始ST干预处理。所有大鼠于D14处死,观察大鼠体格变化,并留取胫骨生长板进行HE染色及增殖细胞核抗原(PCNA)免疫组织化学半定量分析;双抗夹心ELISA法测血清胰岛素样生长因子-1(IGF-1)水平。结果1.随ST水平增加,大鼠体质量、体长、胫骨长逐渐增加,并以5 000μg/100 g组最明显(Pa<0.05);延长ST作用时间,大鼠体质量、体长、胫骨长逐渐增加,并以13 d组最明显(Pa<0.05)。2.随ST水平增加,生长板总宽度、增殖区宽度、肥大区宽度、增殖区构成比和PCNA阳性细胞数逐渐增加,在200μg/100 g组达最大值,5 000μg/100 g组以上指标均下降。延长ST作用时间,生长板总宽度、增殖区宽度、肥大区宽度、增殖区构成比和PCNA阳性细胞数逐渐增加,10 d组达最大值,13 d组以上指标均下降。3.ST作用后血清IGF-1水平未发生明显改变。结论司坦唑醇可促进GnRHa处理后青春期大鼠生长,在一定的剂量和疗程内,加速生长板老化的效应不明显。ST促进生长的作用不依赖于循环生长激素/IGF-1轴内分泌调控。
Objective To observe the effect of stanozolol（ST） on long bone growth and maturation of pubertal female rats treated with gonadotropin releasing hormone agonist（GnRHa）. Methods At 3 weeks of age ,42 female Sprague - Dawley rats（brood） were divided into 7 groups（ST dosage groups,as 5 000μg/100 g group,200 p,g/100 g group,100μg/100 g group,50μg/100 g group,25 μg/100 g group,solvent control group and blank control group） （n = 6 ）. Forty -eight female rats were divided into 8 groups （ST therapeutic duration ） （n = 6 ）. Rats received 2.5 mg/kg im slow - released GnRHa （ triptorelin, as 2 d group,3 d group,5 d group,7 d group, 10 d group, 13 d group, soluent control group and blank control group） which was repeated every 2 weeks for 2 times ,3 days after the 2^nd GnRHa（ D1 ） , ST dosage groups were subcutaneously administrated ST at the various dosage daily（ D1 - Dl3 ）. ST therapeutic duration groups were subcutaneously administrated ST at the dosage of 100μg/100 g daily for different duration. All the rats were killed on the D14. On the day of sacrifice,body weight, body length and left tibial length were measured, plasma were taken for determining insulin - like growth factor - 1 （ IGF - 1 ） , fight tibia were fixed, demineralized and processed for paraffin - embedding. Paraff sections were HE stained for growth plate measurements, proliferating cell nuclear antigen（PCNA） on growth plate was analyzed with immunohistochemistry staining and image. Results l. In the 5 000μg/100 g ST dosage group, the weight, Height and tibial length exceeded than those of the other dosage and control groups（ Pa〈0.05 ）. In the 13 d ST therapeutic duration group, the weight, height and tibial length exceeded than those of the other dosage and control groups （ P〈0.05 ）. 2. ST increased the width of total epiphyseal growth plate, proliferating zone, hypertrophic zone and the expression of PCNA. Time - course studies had shown that the effect were maximally stimulated by ST after 10 days of ST therapy and decreased again after longer periods of incubation. ST increased the width dosage - dependently at 25 - 200μg/100 g, maximally stimulatory concentrations of ST was 200μg/100g, and decreased again after higher concentration of ST. 3. Serum IGF - 1 concentrations were unaffected by ST administration. Conclusions ST enhances the long bone growth of pubertal female rat treated with GnRHa. The effect of ST on the proliferation of chondrocytes of pubertal female rat treated with GnRHa in vivo does not relate to GH/IGF - 1 axia.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2009年第8期589-592,共4页
Journal of Applied Clinical Pediatrics
