基于PPARγ/LXRα/ABCG1信号通路探讨黄芪总皂苷-荷叶总生物碱防治高脂血症的机制  

Mechanism of Total Saponin of Astragali Radix and Total Alkaloids of Nelumbinis Folium Against Hyperlipidemia Based on PPARγ/LXRα/ABCG1 Signaling Pathway

作　　者：张誉方 陈健 张一昕 李思潼 王亚芬 张永奇 石铖 ZHANG Yufang;CHEN Jian;ZHANG Yixin;LI Sitong;WANG Yafen;ZHANG Yongqi;SHI Cheng(College of Pharmacy,Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Hebei International Joint Research Center of Chinese Medicine Resource Utilization and Quality Evaluation,Shijiazhuang 050200,China;School of Basic Medicine,Hebei University of Chinese Medicine,Shijiazhuang 050200,China)

机构地区：[1]河北中医药大学药学院,石家庄050200 [2]河北省中药资源利用与质量评价国际联合研究中心,石家庄050200 [3]河北中医药大学基础医学院,石家庄050200

出　　处：《中国实验方剂学杂志》2024年第13期37-44,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：河北省自然科学基金面上项目(H2020423028);河北省高等学校科学研究计划重点项目(ZD2021079);河北中医药大学大学生创新创业训练计划项目(202314432025)。

摘　　要：目的:观察黄芪总皂苷-荷叶总生物碱配伍对高脂血症大鼠胆固醇逆转运(RCT)的影响,探讨其作用机制。方法:将60只SD大鼠随机分为正常组、高脂饮食组和黄芪总皂苷-荷叶总生物碱低(17 mg·kg^(-1)+40 mg·kg^(-1))、中(34 mg·kg^(-1)+80 mg·kg^(-1))、高(68 mg·kg^(-1)+160 mg·kg^(-1))剂量组及辛伐他汀(2.1 mg·kg^(-1))组,每组10只。采用高脂饲料连续喂养6周复制高脂血症大鼠模型,从第3周开始除正常组和高脂饮食组给予蒸馏水外,其余各组均灌胃相应药物治疗,给药4周。全自动生化分析仪检测大鼠血脂及肝功能变化;苏木素-伊红(HE)及油红O染色法观察大鼠肝组织病理形态及脂肪变性情况;半自动生化分析仪检测大鼠肝组织和粪便总胆固醇(TC)和总胆汁酸(TBA)含量;实时荧光定量聚合酶链式反应(Real-time PCR)及蛋白免疫印迹法(Western blot)检测大鼠肝组织过氧化物酶体增殖物激活受体γ(PPARγ)、肝X受体α(LXRα)、三磷酸结合盒转运体G1(ABCG1)和胆固醇7α羟化酶(CYP7A1)mRNA和蛋白的表达水平。结果:与正常组比较,高脂饮食组大鼠血清TC、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、TBA、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)的含量或活性显著升高(P<0.01),高密度脂蛋白胆固醇(HDL-C)含量显著降低(P<0.01),肝细胞肿胀明显,部分呈气球样改变,肝细胞内含有大量脂肪空泡和红色脂滴,肝组织和粪便TC和TBA含量显著升高(P<0.01),肝组织PPARγ、LXRα、ABCG1和CYP7A1 mRNA和蛋白的表达显著降低(P<0.01)。与高脂饮食组比较,各给药组大鼠血清TC、TG、LDL-C、TBA、AST、ALT的含量或活性显著降低(P<0.01),HDL-C的含量显著升高(P<0.01),肝细胞肿胀明显减轻,肝组织中气球样变、脂滴空泡和红色脂滴明显减少,肝组织TC和TBA含量明显下降(P<0.05,P<0.01),粪便TC和TBA含量明显升高(P<0.05,P<0.01),肝组织PPARγ、LXRα、ABCG1和CYP7A1 mRNA和蛋白表Objective:To observe the effect of the combination of total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium on reversal cholesterol transport(RCT)in hyperlipidemia rats,and to discuss its mechanism.Method:Sixty SD rats were randomly divided into control group,high-fat diet group,total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium low(17 mg·kg^(-1)+40 mg·kg^(-1)),middle(34 mg·kg^(-1)+80 mg·kg^(-1)),high dose(68 mg·kg^(-1)+160 mg·kg^(-1))groups and simvastatin(2.1 mg·kg^(-1))group,with 10 mice in each group.The Hyperlipidemia model was duplicated by feeding rats with a high-fat diet for 6 weeks.From the 3rd week,except for the control group and the high-fat diet group given distilled water,other groups were given corresponding drugs intragastric treatment for 4 weeks.The changes in blood lipid and liver function of rats were detected by an automatic biochemical analyzer.Hematoxylin-eosin(HE)and oil red O staining were used to observe the pathological morphological changes and steatosis of rat liver tissue.The contents of total cholesterol(TC)and total bile acid(TBA)in rat liver tissue and feces were determined by a semi-automatic biochemical analyzer.The mRNA and protein expression levels of peroxisome proliferatorsactivated receptorsγ(PPARγ),liver X receptorsα(LXRα),ATP-binding cassette transporter G1(ABCG1)and cholesterol 7α-hydroxylase(CYP7A1)in rat liver tissue were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)and Western blot.Result:Compared with the control group,the contents or activities of TC,triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),TBA,aspartate aminotransferase(AST),alanine aminotransferase(ALT)in serum were significantly increased(P<0.01),and the contents of high-density lipoprotein cholesterol(HDL-C)in the high-fat diet group were significantly decreased(P<0.01).The hepatocyte was clearly swollen like ballooning degeneration,with a lot of fat vacuoles and red fat droplets.The contents of TC and T

关 键 词：高脂血症 黄芪总皂苷 荷叶总生物碱 胆固醇逆转运 过氧化物酶体增殖物激活受体γ/肝X受体α/三磷酸结合盒转运体G1信号通路 

分 类 号：R2-0[医药卫生—中医学] R33R289R589.2