蛇床子素对模拟微重力引起的骨质流失的防治作用  

The protective effect of osthole on bone loss induced by simulated microgravity

作　　者：冯秀 何进鹏[2] 华君瑞 李贺[2,3] 石文贵 龙凯琴[1,2] 王菊芳 FENG Xiu;HE Jinpeng;HUA Junrui;LI He;SHI Wengui;LONG Kaiqin;WANG Jufang(School of Pharmacy,Lanzhou University,Lanzhou 730000,China;Key Laboratory of Space Radiobiology of Gansu Province,Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou 730000,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]兰州大学药学院,甘肃兰州730000 [2]甘肃省空间辐射生物学重点实验室中国科学院近代物理研究所,甘肃兰州730000 [3]中国科学院大学,北京100049

出　　处：《中国骨质疏松杂志》2018年第8期1074-1079,共6页Chinese Journal of Osteoporosis

基　　金：国家国际科技合作专项(2015DFR30940);中国科学院西部青年学者B类项目;甘肃省科技计划(145RTSA012和17JR5RA307)

摘　　要：目的研究蛇床子素对模拟微重力导致大鼠骨质流失的防治作用。方法将Wistar大鼠随机分为3组:对照组(Ctrl)、尾吊组(HLS)、尾吊给药组(OST)。4周后取后肢骨用双能骨密度仪及万能试验机分别测量各组股骨骨密度及生物力学,并通过micro CT分析骨小梁参数;用Van Gieson(VG)染色观察胫骨形态变化。通过qRT-PCR检测胫骨骨保护素(OPG)和核因子-κB受体激活剂配体(RANKL)mRNA表达水平。用ELISA试剂盒检测血清中骨特异性碱性磷酸酶(BALP)、骨钙素(OCN)和抗酒石酸酸性磷酸酶-5b(TRACP-5b)的含量变化。结果与对照组相比,尾吊组大鼠股骨骨密度及生物力学参数显著降低(P<0.05),与尾吊组相比,尾吊给药组骨密度及生物力学显著上升(P<0.05);尾吊组骨小梁体积分数(BV/TV)、厚度(Tb.Th)显著降低(P<0.01),间距(Tb.Sp)显著升高(P<0.01),尾吊给药后BV/TV、Tb.Th及Tb.Sp显著降低(P<0.01);VG染色观察尾吊组胫骨骨小梁间隙变大,数量减少,而尾吊给药组骨小梁骨髓腔减少,数量增多;尾吊组血清BALP和OCN浓度显著降低(P<0.05),TRACP-5b浓度显著升高(P<0.05),当给予蛇床子素后,BALP浓度显著升高(P<0.05),而TRACP-5b浓度显著降低(P<0.05);尾吊组胫骨OPG/RANKL比值显著降低(P<0.05),尾吊给药后,OPG/RANKL比值显著升高(P<0.05)。结论蛇床子素可通过促进骨形成和抑制骨吸收两方面有效防治模拟微重力导致的骨质流失。Objective To investigate the effect of osthole on resisting bone loss of rats induced by simulated microgravity.Methods Wistar rats were randomly divided into 3 groups： control（Ctrl）,hindlimb suspension（HLS）,and hindlimb suspension treated with osthole（OST）. After 4-week treatment,bone mineral density（BMD） and biomechanics index of femurs were measured using dual-energy X-ray absorptiometry and universal tester,respectively. The trabecular bone parameters were analyzed using micro CT. The morphology of the tibia was observed with van Gieson staining. The mRNA expression levels of osteoprotegerin（OPG） and receptor activator of NF-κB ligand（RANKL） in the tibia were detected with qRT-PCR. The serum concentrations of BALP,OCN,and TRACP-5 b were determined by ELISA. Results BMD and indexes of biomechanics of the femur decreased significantly in HLS group compared with the control group（P〈0. 05）,which were recovered in OST group to a large extend. Micro CT analyses showed that OST treatment significantly restored the cancellous BMD,trabecular bone volume fraction（BV/TV）,thickness（Tb. Th,P〈0. 01）,and decreased trabecular separation（Tb. Sp,P〈0. 01）. van Gieson staining result also showed the trabecular bone number,separation,and thickness in OST group had a better recovery than in HLS group. Inaddition,OST treatment significantly attenuated HLS-induced up-regulation of TRACP-5 b concentration（P〈0. 05） and downregulation of BALP and OCN concentration（P〈0. 05） in serum. On the other hand,the ratio of OPG/RANKL in the tibia was dramatically enhanced in OST treatment group compared with HLS group（P〈0. 05）. Conclusion OST protects against bone loss induced by simulated microgravity through repressing bone resorption and improving bone formation in vivo.

关 键 词：中医中药 蛇床子素 模拟微重力 骨质流失 尾吊 

分 类 号：R965[医药卫生—药理学]