丹皮酚调控ApoE-/-小鼠胆汁酸代谢发挥抗动脉粥样硬化作用  

Paeonol regulates bile acid metabolism in ApoE mice and reduces atherosclerosis

作　　者：何海 黄翰文 施晓艳 刘玲 刘雅蓉 吴鸿飞 戴敏 HE Hai;HUANG Hanwen;SHI Xiaoyan;LIU Ling;LIU Yarong;WU Hongfei;DAI Min(College of Pharmacy,Anhui University of Chinese Medicine&Anhui Province Key Laboratory of Research and Development of Chinese Medicine,Hefei,Anhui 230012,China)

机构地区：[1]安徽中医药大学药学院中药研究与开发安徽省重点实验室,安徽省合肥市230012

出　　处：《中国动脉硬化杂志》2021年第2期123-128,165,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(81773937)。

摘　　要：目的探究丹皮酚通过调控ApoE-/-小鼠胆汁酸代谢影响FXR-FGF15信号通路,从而影响脂质代谢发挥抗动脉粥样硬化的作用。方法采用高脂饲料喂养ApoE-/-小鼠20周建立动脉粥样硬化斑块模型,造模同时灌胃丹皮酚(200 mg/kg)。油红O染色观察主动脉大体和肝脏组织病理形态学变化;酶法检测血脂和肝脂水平;LC-MS/MS检测小鼠肠道胆汁酸组分变化;Western blot检测小鼠肝脏CYP7A1及回肠FXR、FGF15蛋白的表达。结果丹皮酚显著减轻动脉粥样硬化模型小鼠主动脉斑块面积,减少肝脏脂质沉积;明显降低血清和肝脏中甘油三酯、总胆固醇水平及肝脏系数;升高FXR拮抗剂TαMCA、TβMCA含量,降低FXR激动剂CDCA和LCA含量,抑制肠FXR-FGF15信号通路,诱导肝组织CYP7A1蛋白表达,增加粪便中总胆汁酸外排。结论丹皮酚可能通过影响胆汁酸代谢,抑制FXR-FGF15轴从而促进肝脏胆汁酸合成与排泄,减少胆固醇蓄积,进而实现其抗动脉粥样硬化的作用。Aim To explore the effect of paeonol(Pae) on the FXR-FGF15 signaling pathway by regulating the metabolism of bile acids in ApoE-/- mice, thereby affecting lipid metabolism to play an anti-atherosclerotic effect. Methods ApoE-/- mice were fed high-fat diet for 20 weeks to establish an atherosclerotic plaque model, and the model was created and injected with paeonol(200 mg/kg). Oil red O staining was used to observe the pathomorphological changes of the aorta and liver tissues;Enzymatic method was used to detect the lipid levels of blood and liver;LC-MS/MS was used to detect changes in mouse intestinal bile acid composition;Western blot was used to detect the expression of mouse liver CYP7 A1, ileum FXR and FGF15. Results Paeonol significantly reduced the plaque area of the aorta in atherosclerotic model mice and reduced lipid deposition in the liver;significantly reduced the levels of triglyceride, total cholesterol and liver coefficient in serum and liver;increased the content of FXR antagonists TαMCA and TβMCA, reduced the content of FXR agonists CDCA and LCA, inhibited the intestinal FXR-FGF15 signaling pathway, induced the expression of CYP7 A1 protein in liver tissue, and increased the efflux of total bile acid in feces. Conclusion Paeonol may affect the metabolism of bile acids and inhibit the FXR-FGF15 axis to promote the synthesis and excretion of bile acids in the liver, reduce cholesterol accumulation, and achieve its anti-atherosclerotic effect.

关 键 词：丹皮酚 胆汁酸 动脉粥样硬化 

分 类 号：R5[医药卫生—内科学] R363[医药卫生—病理学]