橘皮苷通过调控OPG/RANK/RANKL信号通路对骨质疏松大鼠骨微结构变化和骨代谢的影响

耿景超; 高男; 刘浩; 郭巍; 杜志国; 丁明斌

橘皮苷通过调控OPG/RANK/RANKL信号通路对骨质疏松大鼠骨微结构变化和骨代谢的影响

Effect of hesperidin on the bone microstructure and bone metabolism in osteoporotic rats by regulating OPG/RANK/RANKL signaling pathway

摘要

摘要:
目的： 探讨橘皮苷通过调控骨保护素（OPG）/核因子κB受体活化因子（RANK）/核因子κB受体活化因子配体（RANKL）信号通路对去卵巢骨质疏松大鼠骨微结构变化及骨代谢的影响。
方法： 将50只大鼠随机分为假手术组（Sham组）、骨质疏松模型组（Model组）、阳性药物阿仑膦酸钠组（ALN组）、低剂量橘皮苷组（L-HES组）和高剂量橘皮苷组（H-HES组），各10只。检测各组大鼠骨密度、骨组织微结构变化，HE染色观察骨组织的形态结构，检测血清骨代谢指标，采用蛋白免疫印迹法检测OPG/RANK/RANKL信号通路中相关蛋白的表达水平。
结果： 与Sham组相比，Model组骨密度和骨小梁厚度（Tb.Th）、骨小梁数目（Tb.N）、骨体积分数（BV/TV）及OPG蛋白表达水平均降低，骨小梁间距（Tb.Sp）和碱性磷酸酶（ALP）、骨钙素（OC）、抗酒石酸酸性磷酸酶5b（TRACP-5b）及RANK、RANKL蛋白表达水平均增加（P ＜ 0.05）。与Model组相比，ALN组、L-HES组、H-HES组骨密度、Tb.Th、Tb.N、BV/TV和OPG蛋白表达水平均增加，Tb.Sp和ALP、OC、TRACP-5b及RANK、RANKL蛋白表达水平均降低（P ＜ 0.05），且H-HES组骨密度、Tb.Th、Tb.N、BV/TV和OPG蛋白表达水平均高于L-HES组，Tb.Sp和ALP、OC、TRACP-5b及RANK、RANKL蛋白表达水平均低于L-HES组（P ＜ 0.05）。
结论： 橘皮苷能改善OP大鼠的骨微结构，调节骨代谢水平，提高骨密度，其机制可能涉及对OPG/RANK/RANKL信号通路调控。

Abstract:
Objective To investigate the effects of hesperidin (HES) on the bone microstructure and bone metabolism in ovariectomized osteoporosis rats by regulating osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/receptor activator of nuclear factor-κB ligand (RANKL) signaling pathway.
Methods Fifty rats were randomly divided into the Sham operation group (Sham group), osteoporosis model group (Model group), positive drug alendronate sodium group (ALN group), low-dose hesperidin group (L-HES group) and high-dose hesperidin group (H-HES group), with 10 rats in each group. The bone mineral density and microstructure changes of bone tissue in five groups were detected. The morphological structure of bone tissue was observed by HE staining. Serum bone metabolism indicators were detected. The expression levels of related proteins in the OPG/RANK/RANKL signaling pathway were detected by Western blotting.
Results Compared with the Sham group, the bone mineral density, trabecular thickness (Tb.Th), trabecular number (Tb.N), bone volume fraction (BV/TV) and expression level of OPG protein in the model group all decreased, and the trabecular spacing (Tb.Sp), alkaline phosphatase (ALP), osteocalcin (OC), tartrate-resistant acid phosphatase 5b (TRACP-5b) and protein expression levels of RANK and RANKL all increased (P ＜ 0.05). Compared with the model group, the bone mineral density, Tb.Th, Tb.N, BV/TV and OPG protein expression levels in the ALN group, L-HES group and H-HES group all increased, while the Tb.Sp and ALP, OC, TRACP-5b and RANK, RANKL protein expression levels all decreased (P ＜ 0.05). Moreover, the expression levels of bone mineral density, Tb.Th, Tb.N, BV/TV and OPG proteins in the H-HES group were higher than those in L-HES group, while the expression levels of Tb.Sp, ALP, OC, TRACP-5b and RANK, RANKL proteins in the H-HES group were lower than those in L-HES group (P ＜ 0.05).
Conclusions Hesperidin can improve the bone microstructure of OP rats, regulate bone metabolism levels, and increase bone mineral density. The mechanism may involve the regulation of the OPG/RANK/RANKL signaling pathway.

HTML全文

参考文献(29)

施引文献

资源附件(0)