异补骨脂素对磷酸三钙颗粒诱导骨溶解抑制作用  

INHIBITION OF TRICALCIUMPHOSPHATE PARTICLES-INDUCED OSTEOLYSIS BY ISOPSORALEN IN MICE

作　　者：宣仙君 毛红娇[1] 宋冰洁[1] 屠琼 周佳虹[1] 杜嘉莉[1] 

机构地区：[1]绍兴文理学院医学院,绍兴312000

出　　处：《营养学报》2016年第3期273-277,284,共6页Acta Nutrimenta Sinica

基　　金：浙江省自然科学基金(No.LY13H060003);浙江省中医药科学研究基金计划(No.2012ZB161)

摘　　要：目的研究异补骨脂素抑制磷酸三钙(tricalciumphosphate,TCP)磨损颗粒诱导小鼠颅骨溶解作用。方法取36只雄性ICR小鼠,随机分为假手术组、TCP颗粒组和异补骨脂素干预组(isopsoralen,20 mg/kg)。采用TCP颗粒诱导小鼠颅骨溶解模型,于术后D2颅顶局部注射异补骨脂素,每周3次,2 w后处死动物取颅骨及其骨膜。通过H.E.染色和抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,TRAP)染色观察颅骨表面炎症反应、破骨细胞形成和骨吸收程度,研究异补骨脂素对TCP颗粒诱导骨溶解的影响;应用ELISA法检测颅骨骨膜TNF-α、IL-1β和IL-6水平,观察异补骨脂素对TCP颗粒诱导的炎症因子释放影响;通过检测骨组织中破骨细胞特异性标志物TRAP和组织蛋白酶K(cathepsin K)活性及其m RNA水平的变化,探讨异补骨脂素对破骨细胞功能的影响。结果异补骨脂素可明显抑制TCP颗粒诱导破骨细胞形成和骨溶解;同时显著降低骨组织中TRAP和cathepsin K的活性及m RNA表达,阻断TCP颗粒诱导的炎症因子TNF-α、IL-1β和IL-6释放。结论异补骨脂素能有效抑制TCP颗粒诱导的骨溶解,可作为防治磨损颗粒诱导骨溶解和关节晚期松动的候选药物,减少磨损颗粒所致的骨溶解和关节松动的发生。Objective To investigate the inhibitory effects of isopsoralen on tricalciumphosphate （TCP） particles- induced calvarial osteolysis in mice. Methods Thirty-six male ICR mice were randomly divided into sham group, TCP group and TCP plus isopsoralen （20 mg/kg） group. A routine calvarial model of osteolysis was established by TCP particles implantation （30 mg） onto the surface of bilateral parietal bones followed by periosteum removal. On the second postoperative day, isopsoralen were locally injected into the calvarium under the periosteum three times a week. After 2 weeks, periosteum was collected to determine the expressions of tumor necrosis factor-a （TNF-a）, interleukin-6 （IL-6） and IL-1β using enzyme-linked immumsorbent assay （ELISA）. The calvaria were obtained for histological and molecular analyses by HE and tartrate resistant acid phosphatase （TRAP） staining. Results Histological analysis showed that an obvious increase in osteoclastogenesis and osteolysis area in the calvaria, indicating that isopsoralen inhibits TCP particles-induced osteolysis. ELISA assay indicated that the TCP particles-induced releases of TNF-α IL-1β and IL-6 were significantly suppressed by isopsoralen treatment. Furthermore, isopsoralen significantly suppressed the activity of TRAP and cathepsin K, and also reduced their mRNA expression in the calvaria of TCP particles-implanted group. Conclusion Isopsoralen inhibits TCP particles-induced calvarial osteolysis in mice, and is potential as a new therapeutic candidate for the prevention and treatment of particle-induced osteolysis and arthrochalasis.

关 键 词：TCP颗粒 破骨细胞 骨溶解 异补骨脂素 

分 类 号：R687.4[医药卫生—骨科学]