五苓散抗高脂饮食诱导的高脂血症作用研究  

Effects of Wuling Powder on Mice with Hyperlipidemia

作　　者：张燕花 李珂[1] 赖威旨 王盈盈 郑迅杰 许勰 楼招欢 ZHANG Yanhua;LI Ke;LAI Weizhi(School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou(310053),China;The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine))

机构地区：[1]浙江中医药大学药学院,杭州310053 [2]浙江中医药大学附属第一医院(浙江省中医院)

出　　处：《浙江中医药大学学报》2024年第12期1482-1491,共10页Journal of Zhejiang Chinese Medical University

基　　金：浙江省中医药科技计划项目(2023ZL379、2022ZA049)。

摘　　要：[目的]观察五苓散对高脂血症(hyperlipidemia,HLP)小鼠的干预作用,探讨其可能的作用机制。[方法]48只雄性ICR小鼠随机分为正常组,模型组,依折麦布组,五苓散低、中、高剂量组。除正常组外,均采用高脂饲料喂养,药物干预组造模的同时分别给予依折麦布、五苓散干预,连续8周。实验期间,观察各小鼠一般体征,检测血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、总胆汁酸(total bile acid,TBA)水平;苏木精-伊红(hematoxylin-eosin,HE)染色、油红O染色检测肝组织脂质沉积情况;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)试剂盒检测小鼠磷脂转运蛋白(phospholipid transfer protein,PLTP)、胆固醇酯转运蛋白(cholesterol ester transfer protein,CETP)表达;免疫组化检测肝脏中胆固醇7α羟化酶(cholesteral 7α-hydroxylase,CYP7A1)表达,超高效液相色谱仪串联三重四极杆质谱仪(ultra-high performance liquid chromatograph coupled triple quadrupole mass spectrometer,UPLC-MS/MS)靶向检测肝组织胆汁酸(bile acid,BAs)水平,并进行质谱多反应监测分析,荧光分析肠道胆汁酸受体(Takeda G protein-coupled receptor 5,TGR5)和法尼醇X受体(farnesoid X receptor,FXR1)表达。[结果]五苓散能抑制HLP小鼠体质量增加。在实验第4周,低剂量五苓散显著降低HLP小鼠TC水平(P<0.01),各剂量五苓散显著降低HLP小鼠TG水平(P<0.01);实验第8周,高剂量五苓散升高HLP小鼠TG水平(P<0.05),但对TC、HDL-C、LDL-C表达水平的改善不明显(P>0.05)。五苓散减少HLP小鼠肝细胞脂肪空泡及脂滴数量。中、高剂量五苓散上调HLP小鼠PLTP水平(P<0.01),低、高剂量五苓散上调小鼠CETP水平(P<0.05,P<0.01),降低血清TBA水平,升高CYP7A1的表达水平(P<0.01),并逆转高脂饮食引起的BAs代谢紊乱,同时抑制�[Objective]To investigate the protective effect of Wuling Powder on hyperlipidemic(HLP)mice and the underlying mechanism.[Methods]Forty-eight male ICR mice were randomly divided into six groups:normal,model,Ezetimibe and Wuling Powder low,middle,high dose groups.Mice in all groups were treated with a high-fat diet for 8 weeks,except for normal group.Meanwhile,the mice in drug intervention groups were treated with Ezetimibe or Wuling Powder.General physical signs of mice in each group were observed and recorded,total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and total bile acid(TBA)were detected.Liver lipid deposition was detected by hematoxylin-eosin(HE)staining and oil red staining.Cholesterol ester transfer protein(CETP)and recombinant phospholipid transfer protein(PLTP)was detected with enzyme-linked immunosorbent assay(ELISA).Immunohistochemistry was used to detect the expression of cholesterol 7α-hydroxylase(CYP7A1)in the liver.Ultra-high performance liquid chromatograph coupled triple quadrupole mass spectrometer(UPLC-MS/MS)was applied to measure bile acid(BAs)levels in liver tissue.Expression of intestine Takeda G protein-coupled receptor 5(TGR5)and farnesoid X receptor(FXR1)was detected with fluorescence analysis.[Results]Wuling Powder could inhibit the increase in body weight of mice induced by high-fat diet.In the 4th week,low dose group of Wuling Powder reduced TC level(P<0.01),each group of Wuling Powder reduced the level of TG(P<0.01);in the 8th week,high dose of Wuling Powder could increase the level of TG(P<0.05),there was no statistical significance in the level of TC,HDL-C and LDL-C(P>0.05).Wuling Powder could reduce hepatic cell fat vacuoles and number of lipid droplets;middle and high doses of Wuling Powder could increase the level of PLTP(P<0.01),low and high doses of Wuling Powder could increase the level of CETP(P<0.05,P<0.01),reduce serum level of TBA,and increase immunohistochemical detection of CYP7A1 expression

关 键 词：五苓散 高脂血症 总胆固醇 甘油三酯 胆固醇酯转运蛋白 磷脂转运蛋白 总胆汁酸 胆固醇7α羟化酶 

分 类 号：R331[医药卫生—人体生理学]