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糖皮质激素对肾上腺次全切大鼠维生素D代谢的影响

Effects of glucocorticoid on vitamin D metabolism in subtotal adrenalectomized rats

摘要:

目的 观察大鼠肾上腺次全切以及给予不同剂量糖皮质激素对维生素D代谢的影响.方法 40只2~3月龄Sprague-Dawley大鼠利用随机数字表法分为A、B、C、D和E组.A组为空白对照组,行假手术,保留完整的肾上腺.B、C、D、E为手术模型组,行肾上腺次全切除术.术前各组大鼠分别肌肉注射维生素D310 000U/100 g体重,连续注射3d.术后2周C、D、E组分别给予小剂量(0.1 mg· 100 g体重-1·d-1)、中剂量(0.5 mg· 100 g体重-1·d-1)、大剂量(1.0 mg· 100 g体重-1·d-1)泼尼松灌胃处理,用药4周.A、B组灌用同等体积生理盐水.术前及术后每隔2周分别在内眦静脉采血并留取24 h尿,测定血钙、磷、骨钙素、1,25(OH)2D3等指标.结果 术后2周与术前相比,各手术模型组血皮质醇水平明显降低而促肾上腺皮质激素显著升高,血钙、磷、碱性磷酸酶、骨钙素、1,25(OH)2D3、尿钙、磷显著降低(P均<0.05).补充不同剂量的泼尼松2周后,C、D、E组大鼠与B组相比血1,25(OH)2D3水平均显著增加(P均<0.05),仍低于A组1,25(OH)2D3水平,但差异无统计学意义.用药4周后,与A组相比,只有C组血清1,25(OH)2D3水平基本恢复正常(P>0.05),而D组和E组血清1,25(OH)2D3水平出现进一步降低的趋势,但差异均无统计学意义(P均>0.05).结论 肾上腺次全切除术后可以成功建立大鼠肾上腺皮质功能减退模型.低剂量、短时间应用糖皮质激素对活性维生素D转化有刺激作用,而中、大剂量或长时间应用可以抑制活性维生素D的转化,进而加重骨钙丢失.

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abstracts:

Object To investigate the effects of glucocorticoid on vitamin D metabolism in subtotal adrenalectomized rats.Methods Forty Sprague-Dawley rats were divided into five groups (group A,B,C,D,and E).Group A was control group,and rats in this group were given a sham-operation,in which the whole adrenal gland was maintained.The others were model groups and rats in these groups were given subtotal adrenalectomy.All rats were given vitamin D3 10 000 IU/100 g body weight by intramuscular injection before the experiment.Two weeks after the operation,the rats in group C,D and E were treated with different doses of prednisone:0.1 mg· 100 g body weight-1· d-1,0.5 mg· 100 g body weight-1· d-1 and 1 mg· 100 g body weight-1· d-1,respectively.The rats in group A and B were given equivalent normal saline.Samples were taken every other week.Results Compared with pre-operation,cortisone decreased and adreno-cortico-tropic-hormone (ACTH) was elevated in the model groups,while the serum Ca,P,osteocalcin (BGP) and 1,25 (OH)2D3 were declined (all P <0.05).After adding different doses of prednisone for two weeks,the 1,25 (OH) 2 D3 levels were markedly increased in group C,D and E,compared with group B (P<0.05),but were lower than that in group A,which had no significant difference(P >0.05).After four weeks ofprednisone intervention,compared with group A,the serum 1,25 (OH)2 D3 levels were almost recovered to the normal level in the low dose group,but in the middle dose group and high dose group,they were further decreased although there were no significant difference(P >0.05).Conclusion The rat model of hypocorticoidism could be established by subtotal adrenalectomy.The application of glucocorticoid in low dose and short time can stimulate the transformation of active vitamin D.While the medium and large dose of glucocorticoid in long time could inhibit the metabolism of active vitamin D,and increase the bone loss.

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