糖皮质激素对大鼠胫骨近端干骺端破骨细胞中大麻素受体1表达的作用

目的 探讨糖皮质激素(GC)性骨质疏松症(GIOP)发病的分子机制.方法 32只雌性SD大鼠按体重随机分为3组:基线组(10只)、GC治疗组(11只)和对照组(11只).干预9周.双能X射线吸收法测量骨密度(BMD);显微CT定量分析右侧胫骨的松质骨BMD和结构;原位杂交和免疫组化检测左侧胫骨近端干骺端大麻素受体1(CB1R)的表达.结果 实验结束时,对照组活体全身BMD[(0.156±0.008)g/cm2]较基线组[(0.147±0.006)g/cm2]显著升高,GC治疗组活体全身BMD[(0.147±0.006)g/cm2]和离体股骨整体BMD[(0.220±0.011)g/cm2]较对照组[(0.156±0.008)g/cm2和(0.240±0.024)g/cm2]明显降低.与基线组和对照组比较,GC治疗组骨小梁体积BMD和组织BMD以及骨小梁的数目和连接度明显下降(P<0.05),而骨小梁的分离度显著增大(P<0.05),骨小梁厚度也增加;GC治疗组破骨细胞中CB1R mRNA和蛋白表达显著增加(P<0.05),且与部分微结构参数密切相关(P<0.05).结论 GC可使大鼠BMD降低,骨微结构衰败.GC上调破骨细胞中CB1R的表达水平,可能是GIOP发病的分子机制之一.

The effects of glucocorticoid on expression of cannabinoid-1 receptors in osteoclasts from tibial proximal metaphysis of rats

Objective To explore the molecular mechanism of glucocorticoid (GC)-induced osteoporosis (GIOP). Methods Thirty-two female SD rats after matching body weight were divided randomly into three groups: baseline group (n = 10), control group (n = 11) and GC-treated group (n = 11). The administration time was 9 weeks. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry. A high resolution micro-CT was used to quantify the densitometric and microarchitectural properties of trabeculae in the proximal metaphysis of right tibia. In situ hybridization histochemistry and immunohistochemistry were used to detect the expression of cannabinoid type 1 receptor (CBI R) in the proximal metaphysis of left tibia. Results At the end of the experiment, whole-body BMD in vivo in the control group [(0. 156±0. 008) g/cm2]was higher than that in the baseline group [(0.147±0.006)g/cm2], while the whole-body BMD in vivo [(0.147±0.006) g/cm2]and total BMD in vitro at femurs in the GC-treated group [(0.220±0.011) g/cm2]was lower than those in the control group [(0. 240±0. 024)g/cm2]. Compared with the baseline group and control group, there was a remarkable decrease in the volumetric BMD, tissue BMD, trabecular number and trabecular connectivity (P<0.05) in the GC-treated group, while there was a significant increase in trabecular separation (P < 0. 05) and trabecular thickness also increased in the proximal metaphysis of tibiae in the GC-treated group. The expression level of CB1R mRNA and protein in osteoclasts in the GC-treated group was markedly higher than that in the baseline group and control group (P < 0. 05). There was a close correlation between the expression level of CB1R mRNA, protein in osteoclasts and some microarchitectural parameters in the proximal metaphysis in the GC-treated group (P<0.05). Conclusions The administration of GC is associated with a decrease in BMD and deterioration in microarchitecture of trabecular bone in rats tibiae. Glucocorticoid may up-regulate the CB1R expression level in osteoclasts and this may be a kind of molecular mechanism of GIOP.