THE DELETERIOUS EFFECTS OF LONG-TERM CYCLOSPORINE-A, CYCLOSPORINE-G, AND FK506 ON BONE-MINERAL METABOLISM IN-VIVO
THE DELETERIOUS EFFECTS OF LONG-TERM CYCLOSPORINE-A, CYCLOSPORINE-G, AND FK506 ON BONE-MINERAL METABOLISM IN-VIVO
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DOI：
10.1097/00007890-199404270-00016
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发表时间：
1994-04-27
期刊：
影响因子：
6.2
通讯作者：
EPSTEIN, S
中科院分区：
文献类型：
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作者：
CVETKOVIC, M;MANN, GN;EPSTEIN, S
给雄性和雌性大鼠施用环孢霉素A会加速骨重建并导致骨丢失，以及其他副作用。新的免疫抑制剂FK 506和CsG已被合成以抵消CsA的毒性作用，但仍保持临床疗效。我们研究了长期服用这些药物对大鼠骨矿物质代谢的体内影响。将5组Sprague-Dawley大鼠（每组15只）分配为每天灌胃接受：（1）Cs-vehicle;（2）CsA 15 mg/kg b.w.; (3)CsG 15 mg/kg体重; (4)FK 506溶剂;（5）FK 506 5 mg/kg b.w.在第0、14和28天采集血液，用于测量离子钙（Ca 2+）、甲状旁腺激素（PTH）、1，25-（OH）（2）-维生素D和骨钙蛋白（BGP）。在双钙黄绿素标记后第28天取出钛片进行组织形态计量学分析。将免疫抑制剂组与相应的媒介物组进行比较。CsA和CsG均不影响Ca ~（2+）和PTH水平，而FK 506在第28天引起Ca ~（2+）降低和相应的PTH升高（P
Administration of cyclosporine A to male and female rats accelerates bone remodeling and causes bone loss, among other side-effects. The newer immunosuppressant drugs, FK506 and CsG, have been synthesized to counteract the toxic effects of CsA, yet maintain clinical efficacy. We investigated the in vivo effects of long-term administration of these drugs on bone mineral metabolism in the rat. Five groups of Sprague-Dawley rats, 15 per group, were allocated to receive by daily gavage for a period of 28 days: (1) Cs-vehicle; (2) CsA 15 mg/kg b.w.; (3) CsG 15 mg/kg b.w.; (4) FK506 vehicle; (5) FK506 5 mg/kg b.w. Blood was sampled on days 0, 14, and 28 for measurement of ionized calcium (Ca2+), parathyroid hormone (PTH), 1,25-(OH)(2)-vitamin D, and bone gla protein (BGP). Tibiae were removed on day 28 after double calcein labeling for histomorphometric analysis. Immunosuppressant groups were compared with the respective vehicle groups. Neither CsA or CsG affected the levels of Ca2+ or PTH, whereas by day 28 FK506 caused a decrease in Ca2+ and a corresponding rise in PTH (P