马钱苷与黄连素联合用药对糖尿病小鼠骨代谢的影响  

Effects of combined administration of loganin and berberine on bone metabolism in diabetic mice

作　　者：戴璇 叶紫梦玮 刘亚鸽 陈贝贝[1] 朱如愿 夏兵可 张浩[1] 王新祥[2] 王丽丽 张东伟[1] DAI Xuan;YE Zi-meng-wei;LIU Ya-ge;CHEN Bei-bei;ZHU Ru-yuan;XIA Bing-ke;ZHANG Hao;WANG Xin-xiang;WANG Li-li;ZHANG Dong-wei(Diabetes Research Center,School of Traditional Chinese Medicine,Beijing 100029,China;Medical laboratory center,Dongfang Hospital,Beijing 100078,China;Dept of Pharmacology,School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学1.中医学院糖尿病研究中心,北京100029 [2]北京中医药大学东方医院医学实验中心,北京100078 [3]北京中医药大学中药学院中药药理系,北京100029

出　　处：《中国药理学通报》2022年第2期239-247,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81874373,82074235)。

摘　　要：目的探讨马钱苷与黄连素联合用药对糖尿病小鼠骨代谢的影响及其可能的作用机制。方法利用高脂饮食构建糖尿病小鼠模型。马钱苷与黄连素联合干预10周后观察其对小鼠体质量、体脂、血糖、血脂以及血清氧化应激水平的影响。利用Micro-CT扫描小鼠骨微结构,三点弯曲实验评估骨生物力学特征,红外波谱检测骨材料特性,HE及TRAP染色观察骨病理改变,免疫组化法检测各组小鼠晚期糖基化终产物(AGEs)及其受体(RAGE)/核转录因子-κB(NF-κB)信号通路相关蛋白的表达水平。结果马钱苷与黄连素联合给药可明显抑制糖尿病小鼠体质量及体脂率的增加,改善糖耐量、血糖及血脂水平,降低血清氧化应激水平,同时抑制AGEs/RAGE/NF-κB信号通路相关蛋白的表达,改善骨微结构,提高骨质量。结论马钱苷与黄连素联合用药能抑制糖尿病小鼠骨质量下降,其作用机制可能与AGEs/RAGE/NF-κB信号通路有关。Aim To investigate the effects of combined administration of loganin and berberine on bone structure and metabolism in diabetic mice and its potential mechanism.Methods The diabetic ICR mouse model was induced by high fat diet(HFD).After 10 weeks of combined intervention,the effects of loganin and berberine on body weight,body fat rate,blood glucose,blood lipid and serum oxidative stress levels were observed.Bone microstructure was scanned by micro-CT.Biomechanical characteristics of bone were measured by three-point bending test,and material properties were detected by fourier transform infrared(FTIR).The pathological changes were observed by HE and TRAP staining.Protein expressions involved in advanced glycation end products(AGEs)and their receptors(RAGE)/nuclear factor-κB(NF-κB)signaling pathway were detected by immunohistochemistry.Results The combined administration of loganin and berberine could significantly inhibit the weight gain,reduce the levels of blood glucose,blood lipid and oxidative stress,as well as improve glucose tolerance.In addition,combined intervention also decreased the expression levels of the proteins involved in AGEs/RAGE/NF-κB signaling pathway,and improved bone microstructure,finally contributing to increasing bone quality in diabetic mice.Conclusions The combination of loganin and berberine could improve bone metabolism in diabetic mice,which may be related to AGEs/RAGE/NF-κB signaling pathway.

关 键 词：马钱苷 黄连素 肥胖 糖尿病 骨质疏松 AGEs/RAGE/NF-κB信号通路 

分 类 号：R-332[医药卫生] R282.71