Kawaguchi Y, Kawashima H, Ueno K, Izawa Y, Makita T, Kurozumi S, Hashimoto Y, Yamamoto M, Kimura Y, Imamura N, Oda Y, Sakai S, Ogura Y, Kushida K, Inoue T
Endocrinol Jpn. 1979 Jun;26(Suppl):73-9. doi: 10.1507/endocrj1954.26.supplement_73.
A model of experimental renal osteodystrophy was established in the rats with chronic renal failure induced by partial nephrectomy and therapeutic effects of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) were studied. Male Wistar rats weighing 180 g were 5/6 nephrectomized and fed a normal diet (Ca and P : 1%) for 6 months. After the surgery, serum creatinine levels increased 60% and thereafter continued to rise gradually with their growth for 4 to 5 months, followed by rapid increase. The serum phosphorus levels were also elevated concomitantly and the serum calcium concentrations were normal. Marked bone resorption accompanied with hypertrophy of parathyroid glands was observed by histological examinations (Tetrachrome-Fuchsin stain, contact microradiography and H-E stain). The bone resorption seemed to be due to secondary hyperparathyroidism. Treatment with 0.25 micrograms/kg/day p.o. of 1 alpha-OH-D3 for 10 days in the uremic state resulted in remarkable new bone formation which was confirmed by histological examinations. These results clearly demonstrated that the reduction of nephron mass play a critical clue of renal osteodystrophy and 1 alpha-OH-D3 appears to have a good potential for clinical use in patients with renal failure and metabolic bone diseases.
通过部分肾切除诱导大鼠慢性肾衰竭，建立实验性肾性骨营养不良模型，并研究1α-羟维生素D3（1α-OH-D3）的治疗效果。选取体重180 g的雄性Wistar大鼠，切除其5/6的肾脏，给予正常饮食（钙和磷含量均为1%），持续6个月。术后，血清肌酐水平升高60%，此后随着大鼠生长在4至5个月内逐渐持续上升，随后快速升高。血清磷水平也随之升高，而血清钙浓度正常。组织学检查（四色品红染色、接触式微放射摄影和苏木精-伊红染色）观察到明显的骨吸收，伴有甲状旁腺肥大。骨吸收似乎是由继发性甲状旁腺功能亢进引起的。在尿毒症状态下，以每天0.25μg/kg的剂量口服1α-OH-D3，持续10天，组织学检查证实有显著的新骨形成。这些结果清楚地表明，肾单位数量减少是肾性骨营养不良的关键线索，1α-OH-D3在肾衰竭和代谢性骨病患者的临床应用中似乎具有良好的潜力。
