Rapamycin retards growth and causes marked alterations in the growth plate of young rats.
Rapamycin retards growth and causes marked alterations in the growth plate of young rats.
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DOI：
10.1007/s00467-007-0456-8
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发表时间：
2007-07
期刊：
影响因子：
--
通讯作者：
Santos F
中科院分区：
文献类型：
--
作者：
Alvarez-Garcia O;Carbajo-Pérez E;Garcia E;Gil H;Molinos I;Rodriguez J;Ordoñez FA;Santos F
雷帕霉素是一种有效的免疫抑制剂，具有抗肿瘤特性，广泛应用于肾移植领域。为了检验雷帕霉素的抗增殖和抗血管生成活性干扰生长板的正常结构和功能并损害纵向生长的假设，比较了接受2 mg/kg/天腹膜内雷帕霉素（RAPA）或载体（C）14天的4周龄雄性大鼠（n = 10/组）。雷帕霉素显著降低骨纵向生长速率（94 ± 3 vs. 182 ± 3 μm/天）、体重增加（60.2 ± 1.4 vs. 113.6 ± 1.9 g）、摄食量（227.8 ± 2.6 vs. 287.5 ± 3.4 g）和食物效率（0.26 ± 0.00 vs. 0.40 ± 0.01 g/g）。软骨形成改变的迹象，如软骨细胞增殖减少（溴脱氧尿苷标记细胞32.9 ± 1.4 vs. 45.2 ± 1.1%），成熟障碍和肥大（终末软骨细胞高度26 ± 0 vs. 29 ± 0 μm），减少软骨吸收（18.7 ± 0.5 vs. 31.0 ± 0.8个抗酒石酸盐磷酸酶碱性反应细胞/100个终末软骨细胞），与改变的血管侵入的形态学证据一起，在RAPA动物的生长板中观察到。这项研究表明，雷帕霉素可以严重损害快速生长大鼠的身体生长，并扭曲生长板的结构和动力学。当雷帕霉素用于儿童时，必须牢记这些不良反应。
Rapamycin is a potent immunosuppressant with antitumoral properties widely used in the field of renal transplantation. To test the hypothesis that the antiproliferative and antiangiogenic activity of rapamycin interferes with the normal structure and function of growth plate and impairs longitudinal growth, 4-week-old male rats (n = 10/group) receiving 2 mg/kg per day of intraperitoneal rapamycin (RAPA) or vehicle (C) for 14 days were compared. Rapamycin markedly decreased bone longitudinal growth rate (94 ± 3 vs. 182 ± 3 μm/day), body weight gain (60.2 ± 1.4 vs. 113.6 ± 1.9 g), food intake (227.8 ± 2.6 vs. 287.5 ± 3.4 g), and food efficiency (0.26 ± 0.00 vs. 0.40 ± 0.01 g/g). Signs of altered cartilage formation such as reduced chondrocyte proliferation (bromodeoxiuridine-labeled cells 32.9 ± 1.4 vs. 45.2 ± 1.1%), disturbed maturation and hypertrophy (height of terminal chondrocytes 26 ± 0 vs. 29 ± 0 μm), and decreased cartilage resorption (18.7 ± 0.5 vs. 31.0 ± 0.8 tartrate-resistant phosphatase alkaline reactive cells per 100 terminal chondrocytes), together with morphological evidence of altered vascular invasion, were seen in the growth plate of RAPA animals. This study indicates that rapamycin can severely impair body growth in fast-growing rats and distort growth-plate structure and dynamics. These undesirable effects must be kept in mind when rapamycin is administered to children.
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DOI：
10.1083/jcb.126.6.1611
发表时间：
1994-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Amizuka N;Warshawsky H;Henderson JE;Goltzman D;Karaplis AC
通讯作者：
Karaplis AC
影响因子：
4.2
作者：
JOFFE, I;KATZ, I;EPSTEIN, S
通讯作者：
EPSTEIN, S
影响因子：
6.2
作者：
Flechner, SM;Goldfarb, D;Novick, AC
通讯作者：
Novick, AC
影响因子：
4.8
作者：
Latres, E;Amini, AR;Glass, DJ
通讯作者：
Glass, DJ
影响因子：
6.2
作者：
DiJoseph, JF;Fluhler, E;Sehgal, SN
通讯作者：
Sehgal, SN