白芍总苷对共培养诱生的破骨细胞的作用及机制  

Effects of total glucosides of paeony on co-cultured osteoclasts and its mechanisms

作　　者：周玲玲[1] 魏伟[2] 柳璋璞[1] 周聪[1] 刘天阳[1] 周学平[1] 

机构地区：[1]南京中医药大学药学院,江苏省中药药效与安全性评价重点实验室,江苏南京210023 [2]安徽医科大学临床药理研究所,安徽合肥230032

出　　处：《中国药理学通报》2014年第11期1547-1551,共5页Chinese Pharmacological Bulletin

基　　金：江苏省科技厅社会发展项目(No BE2011847)

摘　　要：目的：研究白芍总苷（ TGP）对佐剂关节炎（ AIA）大鼠滑膜成纤维细胞和单核细胞共培养诱生破骨细胞分化的干预作用及机制。方法分离AIA大鼠滑膜成纤维细胞和外周血单核细胞,共培养诱生破骨细胞；分别加入5、50、500、5000 mg·L-1和50 g·L-1的TGP,检测细胞增殖、TRAP活性和骨吸收功能；ELISA法检测上清中IL-1、TNF-α、M-CSF、RANKL的水平；实时定量 PCR测定细胞 ERK、JNK 和 p38的表达。结果 TGP 50～5000 mg·L-1可浓度依赖性地抑制破骨细胞的增殖能力、TRAP活性和骨吸收面积；降低上清中IL-1、TNF-α、M-CSF、RANKL的水平；不同程度抑制破骨细胞ERK、JNK和 p38的表达。结论一定剂量的 TGP可抑制类风湿关节炎破骨细胞的分化和活性,其作用与抑制滑膜成纤维细胞过度分泌细胞因子,进而阻止MAPKs信号途径的活化有关。s：Aim To study the effects of total gluco-sides of paeony （ TGP） on the differentiation of co-cul-tured osteoclasts and the mechanisms of how TGP influ-ences the osteoclasts. Methods The synovial fibro-blasts and monocytes of peripheral blood in adjuvant-induced arthritic rats were separated and co-cultured to induce osteoclasts. The cells were treated with different TGP dosages （5, 50, 500, 5 000 mg·L-1 , and 50 g ·L-1 ） for 48 h. The proliferation, the TRAP activi-ty, and the bone resorption of osteoclasts were ob-served. The levels of IL-1,TNF-α,M-CSF and RANKL in the supernatants of osteoclasts were detected using ELISA. Meanwhile, the expression of ERK, JNK and p38 was detected by real time PCR. Results The ex-periments revealed that 50, 500, 5 000 mg·L-1 TGP inhibited the osteoclast growth, the TRAP activity, and the resorption pit area in a dose-dependent manner. TGP also inhibited the levels of IL-1 , TNF-α, M-CSF and RANKL in the supernatants and the expression of ERK, JNK and p38 in osteoclasts. The appropriate concentrations were 50 mg·L-1 to 5 000 mg·L-1 and had dose-dependent effects within this range. Conclu-sions TGP regulates the differentiation and activity of co-cultured osteoclasts. The effects of TGP are related to its inhibiting the cytokines secretion of synovial fi-broblasts and the activity of MAPK pathways.

关 键 词：白芍总苷 类风湿关节炎 破骨细胞 共培养 细胞因子 信号转导 

分 类 号：R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]