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

ZHANG Qinggang; ZHANG Qinghong; ZHANG Kemin; YAO Ming; TIAN Yueyang; MAO Xiaoli; FENG Yiyun; WANG Hui

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

更新时间：2022-06-21

- Effects of Curcumin on Bone Metabolism Balance in Ovariectomized Osteoporosis Model Rats Based on OPG/ RANKL Signaling Pathway
- China Pharmacy Vol. 31, Issue 17, (2020)
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ZHANG Qinggang, ZHANG Qinghong, ZHANG Kemin, et al. Effects of Curcumin on Bone Metabolism Balance in Ovariectomized Osteoporosis Model Rats Based on OPG/ RANKL Signaling Pathway. [J]. China Pharmacy 31(17).(2020)
DOI：

ZHANG Qinggang, ZHANG Qinghong, ZHANG Kemin, et al. Effects of Curcumin on Bone Metabolism Balance in Ovariectomized Osteoporosis Model Rats Based on OPG/ RANKL Signaling Pathway. [J]. China Pharmacy 31(17).(2020) DOI：

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30mL/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Westernblotting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OPGmRNA及其蛋白的表达量均显著降低，Tb.Sp、SMI以及RANKLmRNA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OPGmRNA及其蛋白的表达量均显著升高，Tb.Sp、SMI以及RANKLmRNA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。

Abstract

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 50 μg（/ kg·d）]， curcumin low-dose ，medium-dose and high-dose groups [group D-F ，55，110，165 μg（/ 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 consecutive 12 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 @qq.com （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.

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

Keywords

OsteoporosisCurcuminBone metabolism balanceOPG/RANKL signaling pathwayRats

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