糖皮质激素通过抑制内皮细胞形成骨血管导致骨质疏松的实验研究  

Glucocorticoid inhibits bone blood vessels formation of endothelial cells directly and leads to osteoporosis

作　　者：申前进 吕珊[3] 阳文新 江一帆 张铮[1] SHEN Qian-jin;LYU Shan;YANG Wen-xin;JIANG Yi-fan;ZHANG Zheng(the Affiliated Nanjing Hospital of Nanjing Medical University,Nanjing,Jiangsu,210000,China;General Hospital of Eastern War Zone,Nanjing,Jiangsu,210000,China;the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu,210000,China)

机构地区：[1]南京医科大学附属南京医院南京市第一医院,江苏南京210000 [2]东部战区总医院(原第八一医院),江苏南京210000 [3]南京医科大学第一附属医院,江苏南京210000

出　　处：《颈腰痛杂志》2019年第6期727-731,共5页The Journal of Cervicodynia and Lumbodynia

基　　金：国家自然科学基金面上项目(编号:81871096)

摘　　要：目的探索糖皮质激素通过抑制内皮细胞(Endothelial progenitor cell,EPCs)形成骨血管导致骨质疏松的作用机制。方法建立应用泼尼松10 mg/m^2·day^-1从2周龄至6周龄每天腹腔注射的小鼠骨质疏松模型,使用micro-CT将对照组和泼尼松组小鼠股骨进行骨量和形态学的扫描分析,免疫荧光分析股骨干骺端H亚型血管的形成。在体外用泼尼松直接作用于内皮细胞,观察内皮细胞小管的形成,并对小管的长度进行定量分析。结果micro-CT扫描显示,泼尼松组小鼠骨量较对照组明显减少;免疫荧光分析股骨干骺端H亚型血管的形成显示,泼尼松组小鼠股骨干骺端H型血管表达下降;体外细胞实验发现,糖皮质激素能够直接抑制内皮细胞形成血管。结论糖皮质激素导致的骨质疏松可能与糖皮质激素能直接抑制内皮细胞形成骨血管有关。Objective To explore the mechanism of glucocorticoid directly inhibiting endothelial cells,affecting the formation of bone vessels and leading to osteoporosis.Methods We established a mouse model of osteoporosis by daily intraperitoneal injection of prednisone 10 mg/m^2/day from the age of 2 weeks to the age of 6 weeks.To determine the bone mass changes,we performed micro-CT scans of the femur of the control and prednisone mice,analyzed bone mass and morphology and used immunofluorescence to analyze the formation of H-type vessels in femoral epiphysis.We applied prednisone directly to endothelial cells in vitro,observed the formation of endothelial tubules,and made quantitative analysis of the length of tubules.Results Micro-CT scan showed that the bone mass of mice in prednisone group was significantly reduced compared with the control group;immunofluorescence analysis of the formation of H-type vessels in femoral epiphyseal region showed that the expression of H-type vessels in femoral epiphyseal region was decreased in prednisone group.In vitro cell experiments,glucocorticoids could directly inhibit endothelial cell angiogenesis.Conclusion Osteoporosis caused by glucocorticoid may be related to the direct inhibition of endothelial cells by glucocorticoid,which in turn affects the formation of bone vessels.

关 键 词：骨质疏松 H亚型血管 内皮细胞 糖皮质激素 骨血管形成 

分 类 号：P437[天文地球—大气科学及气象学]