雷奈酸锶对大鼠应力缺失性骨丢失的防治作用

Effect of Strontium ranelate on stress-absence induced osteoporosis

目的探讨雷奈酸锶对尾悬吊导致的应力缺失性大鼠骨质疏松的防治效果。方法 6月龄SD大鼠30只,随机均分为3组:正常对照组(A组)、尾悬吊组(B组)、雷奈酸锶干预组(C组)。B、C两组大鼠采用尾悬吊法制备应力缺失型骨质疏松大鼠模型,C组给予1 g/(kg·d)雷奈酸锶干预,4周后处死所有大鼠,取左侧股骨检测骨密度,取左侧胫骨制备非脱钙组织切片并行骨形态计量学检测,取右侧股骨和胫骨骨髓细胞体外培养并向成骨细胞诱导分化,取第4代细胞及血清检测骨钙素(OCN)的表达。结果 B组骨密度低于A组,C组高于B组(P<0.05)。B组骨小梁体积(BV/TV)、骨小梁数量(Tb.N)、骨小梁厚度(Tb.Th)低于A、C组,破骨细胞数(Oc.N)、骨吸收长度比(Er.Pm)高于A组,C组骨形成率(BFR/BV)、矿化长度比(L.Pm)高于B组,Er.Pm、Oc.N低于B组(P<0.05)。B、C组OCN m RNA表达水平高于A组,但血清中OCN水平B组低于A、C组(P<0.05)。结论尾悬吊4周可造成大鼠骨丢失,雷奈酸锶可抑制其骨量丢失,作用机制可能与其通过上调OCN的表达促进骨形成有关。

Objective To investigate the preventive effect of Strontium ranelate on stress-absence induced osteoporo-sis in tail-suspended rat. Methods A total of 30 SD rats with average age of 6 month were randomly divided into 3 groups （n=10 in each group）：Group A was normal control group while rats in group B and C were subjected to tail suspension test to establish stress absence models. Rats in group C were administered with Strontium ranelate [1 g/（kg·d）]. All rats were sacri-ficed 4 weeks later. Left femurs were harvested for bone mineral density （BMD） test and prepared for undecalcified tissue sec-tion and thereby bone histomorphometry assessment. Bone marrow from right femurs and tibias were cultured and induced to-wards osteogenic-differentiation. The expression levels of osteocalcin in the fourth-passage cultured bone marrow cells and in blood serum were detected separately. Results Rats in group B showed markedly decreased BMD comparing to those in group A and C（P〈0.05）. Trabecular volume （BV/TV）, number （Tb.N） and thickness （Tb.Th） in group B were lower than those in group A and C;erosion percentage （Er.Pm） and osteoclast number （Oc.N） in group B and C were higher than those in group A;comparing to those in group B, bone formation rate （BFR/BV）, labeled percentage （L.Pm）, were higher in group C, coupled with decreased Er.Pm and Oc.N（P〈0.05）. mRNA expression levels of OCN in group B and C were higher than those of group A. But its level in plasma were lower in group B than those in group A and C（P〈0.05）. Conclusion Tail suspension could induce osteosporosis. Strontium ranelate prevent bone loss in stress-absence osteoporosis in rat induced by tail-suspension for 4 weeks, which might be partially through upregulating the expression of OCN, thereby promoting bone formation.