文献类型：期刊文献

中文题名：基于OPG/RANKL信号通路探讨姜黄素对去势骨质疏松模型大鼠骨代谢平衡的影响

英文题名：Effects of Curcumin on Bone Metabolism Balance in Ovariectomized Osteoporosis Model Rats Based on OPG/RANKL Signaling Pathway

作者：张庆刚[1];张庆红[1];张克民[2];姚明[1];田月洋[3];毛小莉[3];冯宜蒀[4];王卉[3]

第一作者：张庆刚

机构：[1]滨州市中心医院药剂科,山东251700;[2]滨州市中心医院骨外科,山东滨州251700;[3]华中科技大学同济医学院附属武汉中心医院检验科,武汉430014;[4]甘肃中医药大学附属医院关节外科,兰州730020

第一机构：滨州市中心医院药剂科,山东251700

年份：2020

卷号：31

期号：17

起止页码：2119

中文期刊名：中国药房

外文期刊名：China Pharmacy

收录：CSTPCD;;北大核心:【北大核心2017】；

基金：甘肃省自然科学基金资助项目(No.17JR5RA056)。

语种：中文

中文关键词：骨质疏松;姜黄素;骨代谢平衡;骨保护素/核因子κB受体活化因子配体信号通路;大鼠

外文关键词：Osteoporosis;Curcumin;Bone metabolism balance;OPG/RANKL signaling pathway;Rats

摘要：目的:探讨姜黄素对去势骨质疏松模型大鼠骨代谢平衡的影响,并探讨其可能机制。方法:将雌性Wistar大鼠随机分为空白组(A组)、模型组(B组)、雌二醇组[C组(阳性对照),戊酸雌二醇50μg/(kg·d)]和姜黄素低、中、高剂量组[D^F组,55、110、165μg/(kg·d)],每组15只。除A组外,其余各组均采用去卵巢法建立去势骨质疏松模型。造模后,A、B组大鼠均灌胃生理盐水,各给药组灌胃相应药物,体积均为30 m L/kg,每日1次,连续12周。采用酶联免疫吸附测定法检测各组大鼠血清骨代谢标志物[骨特异性碱性磷酸酶、核心结合因子α1、Ⅰ型胶原交联羧基末端肽、Ⅰ型前胶原氨基端前肽、骨钙素]含量,采用实验动物微型CT影像系统检测大鼠骨密度(BMD)和骨小梁结构参数[相对骨体积分数(BV/TV)、骨小梁数量(Tb.N)、骨小梁厚度(Tb.Th)、连接密度(Conn.D)、骨小梁分离度(Tb.Sp)、结构模型指数(SMI)],采用逆转录聚合酶链式反应法和Western blotting法分别检测下丘脑和股骨组织中骨保护素(OPG)和核因子κB受体活化因子配体(RANKL)mRNA及蛋白的表达情况。结果:与A组比较,B组大鼠血清骨代谢标志物含量,BMD和BV/TV、Tb.N、Tb.Th、Conn.D以及OPG mRNA及其蛋白的表达量均显著降低,Tb.Sp、SMI以及RANKL mRNA及其蛋白的表达量均显著升高(P<0.05)。与B组比较,各给药组大鼠血清骨代谢标志物含量,BMD和BV/TV、Tb.N、Tb.Th、Conn.D以及OPG mRNA及其蛋白的表达量均显著升高,Tb.Sp、SMI以及RANKL mRNA及其蛋白的表达量均显著降低,且姜黄素各组效果均呈剂量依赖性(P<0.05或P<0.01)。结论:姜黄素能够改善去势骨质疏松模型大鼠的骨代谢水平,增加其BMD、改善骨小梁微结构、抑制骨吸收;这种作用可能与调控OPG/RANKL信号通路有关。
OBJECTIVE:To investigate the effects of curcumin on bone metabolism balance in ovariectomized osteoporosis model rats,and to investigate its potential mechanism.METHODS:Totally female Wistar rats were randomly divided into blank group(group A),model group(group B),estradiol group[group C(positive control),estradiol valerate 50μg/(kg·d)],curcumin low-dose,medium-dose and high-dose groups[group D-F,55,110,165μg/(kg·d)],with 15 rats in each group.Except for group A,other rats were ovariectomized to establish osteoporosis model.After modeling,group A and B were given normal saline intrgastrically,and administration groups were given relevant medicine intrgastrically 30 mL/kg,once a day,for consecutive12 weeks.The contents of serum bone metabolism markers[BALP,CBF-α1,CTX-Ⅰ,PINP and OC]were determined by ELISA.The bone mineral density(BMD)and trabecular structure indexes[relative bone volume fraction(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),connectivity density(Conn.D),trabecular separation(Tb.Sp)and structure model index(SMI)]were determined by micro CT imaging system.The mRNA and protein expression of OPG and RANKL in hypothalamus and femur were determined by RT-PCR and Western blotting assay.RESULTS:Compared with group A,the contents of serum bone metabolism markers,BMD,BV/TV,Tb.N,Tb.Th,Conn.D,mRNA and protein expression of OPG were decreased significantly in group B,while Tb.Sp,SMI,mRNA and protein expression of RANKL were increased significantly(P<0.05).Compared with group B,the contents of serum bone metabolism markers,BMD,BV/TV,Tb.N,Tb.Th,Conn.D,mRNA and protein expression of OPG were increased significantly in administration groups;Tb.Sp,SMI,mRNA and protein expression of RANKL were decreased significantly,in a dose-dependent manner among curcumin groups(P<0.05 or P<0.01).CONCLUSIONS:Curcumin can improve the level of bone metabolism,increase BMD,improve the trabecular microstructure and inhibit bone absorption in ovariectomized osteoporosis model rats.Its mechanism may be related to the regulation of OPG/RANKL signaling pathway.