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纸质出版:2014
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黄启钊,戚华兵,王晓凤,朱莹,王权,王先行,杜晓兰,陈林.大剂量1,25二羟维生素D3对发育期小鼠骨稳态的影响[J].陆军军医大学学报(原第三军医大学学报),2014,36(08):774-779.
Huang Qizhao,Qi Huabing,Wang Xiaofeng,Zhu Ying,Wang Quan,Wang Xianxing,Du Xiaolan,Chen Lin.Effects of bone homeostasis induced by high-dose 1,25(OH)2D3 in pubertal mice[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(08):774-779.
黄启钊,戚华兵,王晓凤,朱莹,王权,王先行,杜晓兰,陈林.大剂量1,25二羟维生素D3对发育期小鼠骨稳态的影响[J].陆军军医大学学报(原第三军医大学学报),2014,36(08):774-779. DOI:
Huang Qizhao,Qi Huabing,Wang Xiaofeng,Zhu Ying,Wang Quan,Wang Xianxing,Du Xiaolan,Chen Lin.Effects of bone homeostasis induced by high-dose 1,25(OH)2D3 in pubertal mice[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(08):774-779. DOI:
目的 观察大剂量1
25二羟维生素D3[1
25(OH)
2
D
3
]
对小鼠发育期骨稳态的影响。 方法 怀孕13.5 d的C3h小鼠分成3组,每日分别经腹腔注射1%的乙醇溶液(对照组),0.5 ng/g的1
25(OH)
2
D
3
(低剂量组)和5 ng/g的1
25(OH)
2
D
3
(大剂量组),持续至孕鼠分娩。新生小鼠从第3天开始隔天注射相同剂量的1
25(OH)
2
D
3
,连续1个月。观察小鼠出生以及身长、体质量等生长变化情况;1月龄的小鼠分别行X线检查、Micro-CT扫描,胫骨组织石蜡包埋、切片后经HE、藏红固绿染色,行组织学、骨形态计量分析,观察不同分组发育期小鼠骨骼结构及骨代谢的变化情况。 结果 从E13.5 d开始注射不同剂量的1
25(OH)
2
D
3
对孕鼠怀孕过程和小鼠出生没有明显的影响,出生后第7天开始,大剂量组小鼠身长、体质量明显低于对照组(
P
0.05),1月龄时,差异增大,大剂量组身长、体质量显著低于对照组和小剂量组(
P
0.01);X线检测显示1月龄大剂量组小鼠发生病理性骨折(n=10),其余2组未发现;Micro-CT结果提示大剂量组小鼠骨量较对照组显著降低(
P
0.01),低剂量组小鼠仅骨皮质厚度有所增加(
P
0.05);胫骨组织切片形态计量分析显示大剂量组小鼠破骨细胞数量较其余2组显著增加(
P
0.01),而低剂量组破骨细胞数量的增加差异无统计学意义;低剂量组成骨细胞数量较其余2组有明显增加(
P
0.05)。 结论 大剂量1
25(OH)
2
D
3
显著降低C3h小鼠骨量,同时使骨皮质菲薄,骨骼质量变差,从而易骨折。这种作用主要是通过促进破骨细胞的形成实现的。
Objective To investigate the effects of high-dose 1
25-dihydroxy-vitamin D
3
[1
25(OH)
2
D
3
]
on the bone homeostasis of mice in puberty. Metho
ds Pregnant C3h mice were allocated in 3 groups with intraperitoneal (i.p.) injection of 1% ethanol (control group)
0.5 ng/g 1
25(OH)2D3 (low-dose group) and 5 ng/g 1
25(OH)
2
D
3
(high-dose group)
respectively
from E13.5 until delivery. The newborns of each group were injected with the same dose of 1
25(OH)
2
D
3
as their mothers did from day 3 after birth
every 2 days
to 1 month. The body weight and length of the newborns were recorded per week. All mice were subjected to X-ray filming and Micro-CT scanning at 1 month and then sacrificed. The tibiae were dissected and decalcified for histological and histomorphometry analysis. Results The injection of 1
25(OH)
2
D
3
from E13.5 had no significant effect on pregnancy and birth. Compared with the control group
the mice in the high-dose group had significantly shortened body length and lightened body weight from day 7 after birth (
P
0.05). At 1 month after birth
the significant differences were enlarged (
P
0.001). X-ray filming showed spontaneous bone fracture of mice with high-dose 1
25(OH)
2
D
3
injection
which did not exist in other groups. Micro-CT scanning demonstrated a significant decrease in bone volume of mice in the high-dose group (
P
0.001)
while in the low-dose group only the thickness of cortical bone had increased (
P
0.05). Histological analysis revealed significantly increased number of osteoclasts in the high-dose group compared with other groups (
P
0.001)
while only a slight increase which had no statistic significance in the number of osteoclasts from the low-dose group was detected. Only mice from the low-dose group had significantly increased osteoblasts (
P
0.05). Conclusion High dose of 1
25(OH)
2
D
3
results in decreased bone volume and compromised bone integrity
leading to higher risk of bone fracture. These negative effects may predominantly result from an increase in the p
opulation of osteoclasts.
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