中国骨质疏松杂志

小檗碱联合绿原酸抗骨质疏松的作用机制

Study on the mechanism of the anti-osteoporosis effect of berberine combined with chlorogenic acid

DOI：10.3969/j.issn.1006-7108.2023.07.004

中文关键词: 小檗碱绿原酸骨质疏松 Wnt3a/β-catenin信号通路

英文关键词:berberine chlorogenic acid OVX-induced osteoporosis Wnt3a/β-catenin signaling pathway

基金项目:国家自然科学基金青年基金(82102207)；山西省应用基础研究计划青年项目(20210302124036)

作者	单位
张晓1，2 刘俊瑾1，2 邵云云1，2 常壮鹏1，2* 侯锐钢1，2	1.山西医科大学第二临床医学院，山西太原 030001 2.山西医科大学第二医院药学部，山西太原 030001

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中文摘要:

目的研究小檗碱联合绿原酸对MC3T3-E1细胞分化作用及对绝经后骨质疏松小鼠的干预作用，并探讨其可能的机制。方法观察小檗碱、绿原酸及两药联用对MC3T3-E1细胞增殖和分化能力的影响，并检测细胞中Wnt3a、β-catenin及成骨分化相关基因mRNA的表达水平。在体构建绝经后骨质疏松症小鼠模型，随机分为模型组、小檗碱组、绿原酸组及两药联用组，同时设置假手术组为对照，尾静脉给药8周后处死小鼠，检测其血清BALP、BGP含量，Micro-CT扫描观察小鼠股骨微结构变化，免疫组织化学法检测小鼠股骨Wnt3a和β-catenin蛋白表达，HE染色观察小鼠重要器官的组织病理结构变化。结果与正常组相比，小檗碱组、绿原酸组及两药联用组对MC3T3-E1细胞增殖率无明显影响，但均可促进MC3T3-E1细胞成骨分化能力和矿化水平，以两药联用组最明显；并且两药联用组能显著升高Wnt3a、β-catenin、ALP、Runx2、OPN和OCN mRNA的表达(P＜0.01)。体内实验表明，与模型组相比，两药联用组小鼠血清BALP、BGP含量明显降低，股骨微观结构得到明显改善，股骨Wnt3a和β-catenin蛋白表达明显升高(P＜0.05)，并对小鼠重要器官组织切片无明显损伤性改变，表现出良好的生物安全性。结论小檗碱联合绿原酸可促进MC3T3-E1细胞成骨分化和改善去势小鼠部分骨质疏松表型特征，其机制可能与激活Wnt3a/β-catenin信号通路有关。

英文摘要:

Objective To study the effect of berberine (Ber) combined with chlorogenic acid (CA) on the differentiation of MC3T3-E1 cells and the intervention effect on postmenopausal osteoporosis mice, and to explore the possible mechanism. Methods The effects of Ber, CA, and Ber+CA on the proliferation and differentiation capacity of MC3T3-E1 cells were observed. The mRNA expression levels of Wnt3a, β-catenin and osteogenic differentiation-related genes in MC3T3-E1 cells were detected. Forty female mice were randomly divided into sham operation group, osteoporosis model group, Ber group, CA group, and Ber+CA group. They were sacrificed 8 weeks after caudal intravenous administration. Serum BALP and BGP contents of the mice were detected. The microstructure changes of the femur were observed with micro-CT scanning. The protein expressions of Wnt3a and β-catenin in the femur was detected with immunohistochemistry. The histopathological structure changes of the important organs were observed by HE staining. Results The proliferation rate of MC3T3-E1 cells were not influenced in Ber group, CA group, and Ber+CA group, bu the osteogenic differentiation ability and mineralization level of MC3T3-E1 cells were promoted, which was the most obvious in Ber+CA group. Moreover, the mRNA expressions of Wnt3a, β-catenin, ALP, Runx2, OPN, and OCN significantly increased in the Ber+CA group (P<0.01). In vivo experiments showed that compared with those in the model group, serum contents of BALP and BGP in the Ber+CA group significantly reduced, the protein expressions of Wnt3a and β-catenin significantly increased, and the microstructure of femoral tissue was significantly improved in the Ber+CA group (P<0.05). Moreover, Ber+CA had no obvious damage to the important organ tissue sections of mice, indicating good biosafety. Conclusion Ber combined with CA promotes osteogenic differentiation of MC3T3-E1 cells and improves partial osteoporosis phenotypic characteristics in ovariectomized mice. The mechanism may be related to the activation of Wnt3a/β-catenin signaling pathway.

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