摘要
目的:探讨木豆素单体对骨质疏松症(OP)等类溶骨性疾病的防治作用及具体机制。方法:提取并培养小鼠BMM和RAW264.7细胞,进行MTS、TRAc P染色、荧光素酶基因报告、PCR、Western blot、ROS清除、钙离子震荡等体外实验;建立OVX小鼠模型,观察Micro-CT形态学,HE、TRAc P染色等组织形态学试验,探讨木豆素预防OVX小鼠的骨丢失作用;最后通过木豆素胶囊治疗40例OP患者(时间0.5-1.1年),观察治疗前后患者骨密度的改变情况。结果:木豆素可抑制RANKL诱导的破骨细胞形成和骨吸收;抑制破骨标志基因以及NF-κB和NFAT通路上下游中的蛋白表达水平。另外,还可抑制活性氧(ROS)以及钙离子震荡反应。此外,通过小鼠卵巢切除动物模型实验,发现木豆素能够扭转由卵巢切除术引起的骨丢失,实验组Micro-CT见骨量增加、TRAc P染色中破骨细胞减少、HE染色中骨量增多等表现。临床研究发现,木豆素胶囊可改善OP患者的骨密度(P<0.01)。结论:木豆素通过抑制RANKL诱导的破骨细胞形成和破骨细胞的功能来减少OVX小鼠的骨丢失,从而预防骨质疏松。
Objective： To investigate the preventive and therapeutic effects and mechanism of how cajaninstilbene acid（CSA） acts on osteoporosis（OP） and other osteolytic diseases. Methods： BMM and RAW264.7 cells of mouse were extracted and cultured for the assays of MTS, TRAc P staining, luciferase, RT-PCR, Western blot, ROS and Ca2＋ oscillation in vitro. OVX mouse model was established to observe the morphology of Micro-CT. In addition, the effects of CSA on the bone loss in OVX mice were investigated by HE, TRac P staining. Finally, 40 OP patients（0.5 to 1.1 years＇ fellow up） were treated with CSA capsules for the observation of the changes of bone mineral density（BMD） before and after the treatment. Results： CSA could suppress RANKL-induced osteoclast genesis, bone resorption, osteoclast-specific gene expressions as well as the protein levels in the RANKL-activated NF-κB and NFAT signal pathways. In addition, CSA was capable of blocking RANKL-induced reactive oxygen species（ROS） activity and calcium oscillation in the osteoclasts. Animal experiment showed that CSA was able to reverse bone loss caused by ovariectomy. In the CSA group, Micro-CT and HE staining showed increased bone mass while decreased osteoclasts in TRAc P staining. The clinical assay showed CSA capsules increased the BMD in osteoporotic patients（P〈0.01）. Conclusion： CSA can reduce bone loss by inhibiting RANKL-induced osteoclast genesis and osteoclast function, thereby preventing osteoporosis.
作者
孙友强
刘予豪
陈雷雷
王超
珍妮弗.迪克娜
邹许亭
洪志楠
杨帆
文森特.库克
周驰
邵敏
王海彬
徐家科
何伟
SUN You-qiang;LIU Yu-hao;CHEN Lei-lei;WANG Chao;Jennifer. Tickner;ZOU Xu-ting;HONG Zhi-nan;YANG Fan;Vincent. Kuek;ZHOU Chi;SHAO Min;WANG Hai-bin;XU Jia-ke;HE Wei(Lab of Orthopedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China;Department of Orthopedics, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China;School of Pathology and Laboratory Medicine, The University of Western Australia, Perth 6009, Australia;Department of Orthopedics, Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510240, China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2018年第5期2166-2173,共8页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.81673999)
广东省自然科学杰出青年基金项目(No.2015A030306037)
广州中医药大学优秀博士论文培育基金项目(No.A1-AFD01817Z0713)
广州中医药大学第一临床学院优秀博士论文培育基金项目(No.YB201601)~~
