文献类型：期刊文献

中文题名：萸蓉壮骨膏调控JNK-OPG/RANKL轴改善绝经后骨质疏松症机制

英文题名：Exploring the protective mechanism of Yurong Zhuanggu Gao on postmenopausal osteoporotic rats based on JNK-OPG/RANKL signaling axis

作者：刘馨鸿[1];郭超[1];宋冰[2,3];白敏[2,3];汪湛东[2,3];赵泓彰[2,3];王琼[2,3];张延英[2,3];赵兴绪[1]

第一作者：刘馨鸿

机构：[1]甘肃农业大学动物医学院,甘肃兰州730000;[2]甘肃中医药大学,甘肃兰州730000;[3]甘肃省实验动物行业技术中心,甘肃兰州730000

第一机构：甘肃农业大学动物医学院,甘肃兰州730000

年份：2025

卷号：31

期号：2

起止页码：188

中文期刊名：中国骨质疏松杂志

外文期刊名：Chinese Journal of Osteoporosis

收录：;北大核心:【北大核心2023】；

基金：甘肃省教育科技创新项目(2023A-080);甘肃省科技重点研发计划项目(23YFFA0068)。

语种：中文

中文关键词：萸蓉壮骨膏;绝经后骨质疏松症;JNK-OPG/RANKL信号轴;骨形成;骨吸收

外文关键词：Yurong Zhuanggu Gao;postmenopausal osteoporosis;JNK-OPG/RANKL signaling axis;bone formation;bone resorption

摘要：目的明确药食同源新产品萸蓉壮骨膏对绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠的骨保护作用,并基于JNK-OPG/RANKL信号轴探讨其机制。方法选取60只2月龄SPF级SD雌性大鼠,采用随机数字表法将大鼠分为Sham(假手术)组(n=10)、造模组(n=50)。造模组大鼠全部采用去势造模法复制绝经后骨质疏松模型,模型评价成功后将大鼠随机分为模型组(OVX)、阿仑膦酸钠组[Alen,6.3 mg/(kg·w)]及萸蓉壮骨膏高[SRH,10.8 g/(kg·d)]、中[SRM,5.4 g/(kg·d)]、低剂量[SRL,2.7 g/(kg·d)]组。持续给药12周后取材。采用Micro CT检测骨微结构,苏木精-伊红染色法(hematoxylin-eosin staining,HE)观察股骨组织病理形态;生化和酶联免疫吸附测定(ELISA)法检测大鼠血清Ca、Pi、PTH、1,25(OH)2D 3、BGP、B-ALP、PYD、DPD的水平;TRAP观察破骨细胞生长情况;蛋白免疫印迹(WB)及实时逆转录聚合酶链反应(RT-PCR)法检测大鼠股骨组织中JNK、OPG、RANKL、RANK蛋白和mRNA表达水平。结果与Sham组比较,OVX组大鼠骨微结构指标BMD、BV/TV、Tb.Th和Tb.N显著降低(P<0.05),Tb.Sp明显升高(P<0.05);骨小梁断裂,骨髓腔扩大,脂肪组织累积增加,破骨细胞生长;血清Ca、PTH、PYD、DPD水平均升高(P<0.05),Pi、1,25(OH)2D 3、BGP、B-ALP水平均降低(P<0.05);大鼠骨组织中OPG、JNK蛋白和mRNA表达水平显著降低(P<0.05),RANK、RANKL蛋白和mRNA表达水平显著升高(P<0.05);与OVX组比较,Alen、SRM、SRH组大鼠骨微结构指标BMD、BV/TV、Tb.Th和Tb.N明显增加(P<0.05),Tb.Sp明显降低(P<0.05);各给药组模型大鼠骨组织病理结构均有不同程度改善;Alen、SRM、SRH组大鼠血清Ca、PTH、PYD、DPD水平均降低(P<0.05),Pi、1,25(OH)2D 3、BGP、B-ALP水平均升高(P<0.05);Alen、SRM、SRH组大鼠骨组织中OPG、JNK蛋白和mRNA表达水平明显升高(P<0.05),RANK、RANKL蛋白和mRNA表达水平明显降低(P<0.05)。结论药食同源新产品萸蓉壮骨膏能改善PMOP大鼠骨微结构和降低破骨细胞活性,促进骨形成,其具体机制与萸蓉壮骨膏调控JNK-OPG/RANKL信号轴及关键分子表达密切相关。
Objective To clarify the bone protection effect of Yurong Zhuanggu Gao on PMOP rats,and explore its mechanism based on JNK-OPG/RANKL signal axis.Methods Sixty 2-month-old SD female rats were selected and divided into Sham group(n=10)and modeling group(n=50)by randomized numerical table method.All the rats in the modeling group were replicated in the postmenopausal osteoporosis model by the depopulation modeling method,and after successful model evaluation,the rats were randomly divided into the modeling group,alendronate tablet group[Alen,6.3 mg/(kg·w)],and the Sham high[SRH,10.8 g/(kg·d)],medium[SRM,5.4 g/(kg·d)],and low-dose[SRL,2.7 g/(kg·d)]groups.Samples were taken after 12 weeks of continuous administration.Micro CT was used to detect the bone microstructure,and HE was used to observe the histopathological morphology of the femur;biochemical and ELISAs were used to detect the levels of serum Ca,Pi,PTH,1,25(OH)2D 3,BGP,B ALP,PYD,DPD;TRAP to observe the growth of osteoclasts;WB and RT-PCR to detect the expression levels of JNK,OPG,RANKL,RANK proteins and mRNAs in the femoral tissues of rats.Results Compared with the Sham group,the bone microstructural indexes BMD,BV/TV,Tb.Th and Tb.N were significantly decreased in the OVX group(P<0.05),and Tb.Sp was significantly elevated(P<0.05);Trabecular bone breaks,enlarged bone marrow cavity,increased accumulation of adipose tissue,and osteoclasts growth;in the OVX group,the serum Ca,PTH,PYD,DPD levels were increased(P<0.05),and the levels of Pi,1,25(OH)2D 3,BGP,B-ALP were decreased(P<0.05);the levels of OPG,JNK protein and mRNA expression in the bone tissue of rats in the OVX group were significantly decreased(P<0.05),and the levels of RANK,RANKL protein and mRNA expression were significantly increased(P<0.05);Alen,SRM and SRH group,serum Ca,PTH,PYD,DPD levels were reduced(P<0.05),and the levels of Pi,1,25(OH)2D 3,BGP,B-ALP were elevated(P<0.05);the levels of OPG,JNK protein and mRNA expression were significantly elevated in the bone tissues of the rats in Alen,SRM,and SRH groups.and mRNA expression levels were significantly higher(P<0.05),and RANK,RANKL protein and mRNA expression levels were significantly lower(P<0.05).Conclusion As a new product with the same origin as medicine and food,Yurong Zhuanggu Gao can improve bone microstructure,reduce osteoclast activity and promote bone formation in PMOP rats.The specific mechanism of Yurong Zhuanggu Gao is closely related to the regulation of JNK-OPG/RANKL signal axis and key molecular expression.