吴茱萸次碱改善MAFLD小鼠脂肪肝和骨质疏松的作用  

The effect of rutaecarpine on improving fatty liver and osteoporosis in MAFLD mice

作　　者：张煜皓 李依宁 姜新海 王伟志 李顺旺 盛任 雷丽娟 张语嫣 王晶锐 魏欣玮 许艳妮 林燕[3] 唐琳 司书毅 ZHANG Yu-hao;LI Yi-ning;JIANG Xin-hai;WANG Wei-zhi;LI Shun-wang;SHENG Ren;LEI Li-juan;ZHANG Yu-yan;WANG Jing-rui;WEI Xin-wei;XU Yan-ni;LIN Yan;TANG Lin;SI Shu-yi(Key Laboratory of Biotechnology for Microbial Drugs,State Key Laboratory of Bioactive Substance and Function of Natural Medicines,National Center for Screening Novel Microbial Drugs,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China;Beijing Institute of Chinese Medicine,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China;China Medico Corporation,Tianjin 300301,China)

机构地区：[1]中国医学科学院、北京协和医学院医药生物技术研究所,卫健委微生物药物生物技术重点实验室,天然药物活性物质与功能国家重点实验室,国家新药(微生物)筛选实验室,北京100050 [2]首都医科大学附属北京地坛医院,北京100015 [3]首都医科大学附属北京中医医院,北京市中医药研究所,北京100010 [4]盛实百草药业有限公司,天津300301

出　　处：《药学学报》2025年第1期141-149,共9页Acta Pharmaceutica Sinica

基　　金：中国药学会-以岭生物医药创新基金(CPA-B04-ZC-2021-005);中国医学科学院中央级公益性科研院所基本科研业务费(2022-JKCS-10);国家自然科学基金青年基金项目(82404723)。

摘　　要：代谢相关脂肪性肝病(metabolic-associated fatty liver disease,MAFLD)和骨质疏松症(osteoporosis,OP)是两种非常普遍的代谢性疾病。越来越多的实验证据支持MAFLD和OP之间有病理生理联系,MAFLD常伴随OP的发生。吴茱萸次碱(rutaecarpine,RUT)是中药吴茱萸的主要活性成分之一,课题组前期研究发现RUT具有降脂、抗炎和抗动脉粥样硬化作用,并且可以改善大鼠的OP。但是,RUT能否同时改善MAFLD小鼠的脂肪肝和OP症状,目前尚待研究。本研究利用高脂饲料饮食(high fat diet,HFD)4个月喂养的C57BL/6小鼠构建MAFLD模型。灌胃给予RUT低剂量(5 mg·kg^(-1))和高剂量(15 mg·kg^(-1))4周,实验结束时评价RUT在体内对肝脏脂肪变性和骨代谢的影响(本实验获得中国医学科学院医药生物技术研究所动物伦理委员会批准,批准号:IMB-20190124D303)。研究结果表明,RUT治疗显著减少了肝脏脂肪变性和脂质积累,同时显著减少骨丢失并促进了骨形成。综上,本研究表明RUT具有改善MAFLD小鼠的脂肪肝和OP的作用。Metabolic-associated fatty liver disease(MAFLD)and osteoporosis(OP)are two very common metabolic diseases.A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP.MAFLD is often associated with the development of OP.Rutaecarpine(RUT)is one of the main active components of Chinese medicine Euodiae Fructus.Our previous studies have demonstrated that RUT has lipid-lowering,anti-inflammatory and anti-atherosclerotic effects,and can improve the OP of rats.However,whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated.In this study,we used C57BL/6 mice fed a high-fat diet(HFD)for 4 months to construct a MAFLD model,and gave the mice a low dose(5 mg kg^(-1))and a high dose(15 mg:kg^(-1))of RUT by gavage for 4 weeks.The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment[this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences(approval number:IMB-20190124D,03)].The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation,and significantly reduced bone loss and promoted bone formation.In summary,this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

关 键 词：吴茱萸次碱 非酒精性脂肪性肝病 代谢相关脂肪性肝病 骨质疏松症 骨代谢 

分 类 号：R966[医药卫生—药理学]