蜂斗菜素对去卵巢大鼠骨质疏松症的治疗作用及机制研究  

A Study on the Mechanism and Therapeutic Effects of Petasin on Osteoporosis in Ovariectomized Rats

作　　者：姚莉[1] 王晓红[2] 戴余雯 于元军 武延庆 肖吉元[1] YAO Li;WANG Xiaohong;DAI Yuwen;YU Yuanjun;WU Yanqing;XIAO Jiyuan(Lanzhou Universily Second Hospital,Lanzhou 730030,China;Gansu Provincial Hospital of TCM)

机构地区：[1]兰州大学第二医院,兰州730030 [2]甘肃省中医院

出　　处：《西部中医药》2020年第10期17-21,共5页Western Journal of Traditional Chinese Medicine

基　　金：甘肃省自然科学基金(18JR3RA316).

摘　　要：目的:评价蜂斗菜素对去卵巢大鼠骨质疏松症的治疗作用并探讨其作用机制。方法:将60只雌性SD大鼠随机分为假手术组、模型组,尼尔雌醇组,蜂斗菜素高(40 mg/kg)、中(20 mg/kg)、低(10 mg/kg)剂量组,每组10只。灌胃给药,每日1次,连续14周。酶联免疫吸附法(enzyme-linked immune sorbent assay,ELISA)法检测外周血中骨钙素(bone glaprotein,BGP)、降钙素(calcitonin,CT)、骨保护素(osteoprotegerin,OPG)和核因子-κB受体活化因子配体(receptor activator of nuclear factor kappa-B ligand,RANKL)的表达水平,骨密度仪检测腰椎及股骨的骨矿物密度(bone mineral density,BMD),三点弯曲法测定胫骨生物力学指标,免疫印迹(Western blot,WB)检测磷酸化细胞外信号调节激酶1/2(phosphorylated extracellularregulated kinase1/2,P-ERK1/2)、磷酸化蛋白38(phosphorylated protein-38,P-P38)、OPG和RANKL蛋白表达。结果:与假手术组比较,模型组大鼠血清中CT与OPG含量均显著降低(P<0.01),而BGP和RANKL水平均显著升高(P<0.01),腰椎和股骨的骨密度BMD值以及胫骨的最大载荷及最大应力均显著降低(P<0.05),P-ERK1/2、P-P38和OPG蛋白表达均显著降低(P<0.01),RANKL蛋白表达明显升高(P<0.05)。与模型组相比,蜂斗菜素组CT和OPG水平明显著升高,BGP和RANKL水平明显降低,腰椎和股骨BMD值显著升高,胫骨的最大载荷及最大应力均显著增高,差异均具有统计学意义(P<0.05)。蜂斗菜素各组P-ERK1/2、P-P38和OPG蛋白表达均呈剂量依赖性升高(P<0.05),同时蜂斗菜素显著抑制RANKL蛋白的表达(P<0.05)。其中以蜂斗菜素高剂量组效果最强。结论:蜂斗菜素对去卵巢大鼠骨质疏松症有显著的治疗作用,其机制可能与其调节MAPKs-OPG-RANKL信号通路有关。Objective:To assess therapeutic effects of petasin on osteoporosis in ovariectomized rats and discuss its mechanism.Methods:Sixty female SD rats were randomized into sham operation group,the model group,nilestriol group,high(40 mg/kg),moderate(20 mg/kg)and low(10 mg/kg)dosages groups of petasin,intragastric administration,once each day.for 14 weeks consecutively.ELISA method was adopted to detect the expressions of RANKL,OPG,CT and BGP in peripheral blood,dual energy X-ray absorptiometry to measure BMD of lumbar vertebra and femur,three point bending method to detect biomechanical index of tibia,Western blot to detect the expressions of P-ERK1/2.P-P38,OPG and RANKL proteins.Results:Compared with sham operation group,the contents of CT and OPG in the serum of ovariectomized model group lowered notably(P<0.01),while the levels of BGP and RANKL lifted remarkably(P<0.01),BMD of lumbar vertebra and femur,maximum load and maximum stress of tibia reduced notably(P<0.05),the expressions of P-ERK1/2,P-P38 and OPG protein lowered notably(P<0.01),the expressions of RANKL protein rose notably(P<0.05).Compared with the model group,the levels of CT and OPG lifted notably in petasin group.the levels of BGP and RANKL reduced significantly,BMD values of lumbar vertebra and femur rose remarkably,maximum load and maximum stress of tibia enhanced apparently,and the difference showed statistical meaning(P<0.05).The expressions of Phospho-ERK1/2,Phospho-P38 and OPG protein rose in a dose-dependent manner in petasin group(P<0.05),meanwhile petasin could significantly inhibit the expressions of RANKL protein(P<0.05).among them,the effects of high dose group of petasin the strongest.Conclusion:Petasin possesses the notable therapeutic effects on osteoporosis in ovariectomized rats,and its mechanism might be related to regulating MAPKs-OPG-RANKL signaling pathway.

关 键 词：蜂斗菜素 骨质疏松 骨矿物密度 降钙素 骨钙素 骨保护素 核因子-κB 大鼠 动物实验 

分 类 号：R285.5[医药卫生—中药学]