文献类型：期刊文献

中文题名：蛇床子素对TCP颗粒诱导小鼠颅骨溶解的影响

英文题名：Effect of osthole on tricalcium phosphate particles-induced calvarial osteolysis in a mouse model

作者：王青[1];张云[1];毛红娇[1];王金萍[1];贾如如[1];金丽芳[1];戴智睿[1]

机构：[1]绍兴文理学院医学院

年份：2015

卷号：31

期号：12

起止页码：2265

中文期刊名：中国病理生理杂志

外文期刊名：Chinese Journal of Pathophysiology

收录：CSTPCD、、北大核心2014、CSCD2015_2016、北大核心、CSCD

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

语种：中文

中文关键词：磷酸三钙颗粒;破骨细胞;骨溶解;蛇床子素;内质网应激

外文关键词：Trlcalcium phosphate particles ; Osteoclast ; Osteolysis ; Osthole ; Endoplasmic reticulum stress

中文摘要：目的:观察蛇床子素对磷酸三钙(tricalcium phosphate,TCP)颗粒诱导小鼠颅骨溶解的影响。方法:采用TCP颗粒诱导小鼠颅骨溶解模型,于术后第2天颅顶局部注射蛇床子素(osthole)20 mg/kg,每周3次,持续干预2周。干预结束后处死动物取材,应用HE染色和抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,TRACP)染色观察假体周围破骨细胞生成和骨溶解程度;ELISA法检测血清和骨组织中骨转换标志物骨钙素(osteocalcin)水平、碱性磷酸酶(alkaline phosphatase,ALP)和TRACP活性以及骨膜中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)和白细胞介素1β(interleukin-1β,IL-1β)水平。Western blot法检测颅骨组织葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)和CAAT/增强子结合蛋白同源蛋白(CAAT/enhancer binding protein homologous protein,CHOP)的表达变化。结果:蛇床子素可明显抑制TCP颗粒诱导的破骨细胞生成,减少骨溶解面积,显著增加ALP和osteoclacin水平,降低TRAP活性并阻断炎症因子TNF-α、IL-6和IL-1β释放。此外,蛇床子素干预能明显减弱TCP颗粒激活的内质网应激反应。结论:蛇床子素可抑制TCP颗粒诱导的小鼠颅骨溶解,其机制可能与抑制TCP颗粒诱导的内质网应激反应有关。

外文摘要：AIM： To observe the effect of osthole on tricalcium phosphate （TCP） particles-induced calvarial osteolysis in vivo. METHODS： Male ICR mice were randomly divided into sham group, TCP group and osthole group. A mouse calvarial model of osteolysis was established by TCP particles. On the second postoperative day, osthole （20 mg/ kg） was locally injected into the calvarium under the periosteum 3 times a week. Two weeks after osthole treatment, blood and calvaria were collected to determine the level of bone turnover markers such as alkaline phosphatase（ALP） , osteocalcin and tartrate-resistant acid phosphatase （TRACP）. The periosteum was performed to examine the release of tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and IL-1β by ELISA. The calvaria was obtained for histological and molecular analyses. RESULTS： Data from HE and TRACP staining revealed that osthole prevented TCP particles-induced obvious increase in osteoclastogenesis and resorption area in the metaphysis of mouse calvaria. Osthole treatment increased ALP ac- tivity and osteocalcin level, and dncreased the activity of TRACP in the mouse serum compared with TCP group. Further- more, TCP particles-induced the releases of TNF-α, IL-6 and IL-1β were significantly suppressed by osthole treatment In addition, Western blot demonstrated that endoplasmic reticulum （ER） stress markers such as glucose-regulated protein 78 （GRP78） and CAAT/enhancer binding protein homologous protein （CHOP） were significantly up-regnlated in TCP parti- cles-implanted ealvarial mice, indicating that TCP particles triggered an ER stress response in the mouse ealvarial osteolysis model, which obviously attenuated by osthole. CONCLUSION： Osthole inhibits TCP particles-induced calvarial osteolysis in mice, which is mediated by inhibition of ER stress signaling pathway.