芳香新塔花总黄酮通过调控PPARγ/LXRα/ABCA1通路对ApoE^(-/-)动脉粥样硬化小鼠肝脏脂质代谢紊乱的影响  

Effects of total flavonoids of Ziziphora bungeana on liver lipid metabolism disorder in ApoE^(-/-)mouse model of atherosclerosis via PPARγ/LXRα/ABCA1 pathway

作　　者：叶丹[1] 马晓宇 钊浩然 乔会林 张选明[1] YE Dan;MA Xiao-yu;ZHAO Hao-ran;QIAO Hui-lin;ZHANG Xuan-ming(The First Affiliated Hospital to Shihezi University,Shihezi 832000,China;School of Pharmacy,Shihezi University,Shihezi 832000,China)

机构地区：[1]石河子大学第一附属医院,新疆石河子832000 [2]石河子大学药学院,新疆石河子832000

出　　处：《中成药》2023年第11期3577-3582,共6页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金(81960853);国家中医药管理局青年岐黄学者支持项目[国中医药人教函(2020)218]。

摘　　要：目的探究芳香新塔花总黄酮对ApoE^(-/-)动脉粥样硬化小鼠肝脏脂质代谢及对PPARγ/LXRα/ABCA1通路的影响。方法60只ApoE^(-/-)小鼠给予高脂饲料喂养8周后随机分为模型组、阿托伐他汀组(3 mg/kg)及芳香新塔花总黄酮低、中、高剂量组(25、50、100 mg/kg),每组12只。灌胃给予相应剂量药物干预12周,给药同时继续饲喂高脂饲料;另取12只C57BL/6J小鼠为空白组,灌胃给予生理盐水,同时喂养普通饲料。给药结束后,油红O染色观察肝组织脂质沉积情况,HE染色观察主动脉斑块形态,全自动生化分析仪检测血脂水平,ELISA法检测血清IL-18、IL-1β、MCP-1水平,试剂盒检测肝组织TC、TG、NEFA、FC水平,Western blot法检测肝组织PPARγ、LXRα、ABCA1、ABCG1蛋白表达。结果与空白组比较,模型组肝脏脂滴面积增加(P<0.01),血清TC、TG、LDL-C、IL-18、IL-1β、MCP-1水平和肝组织TC、TG、NEFA、FC水平均升高(P<0.05,P<0.01),血清HDL-C水平和肝组织PPARγ、LXRα、ABCA1、ABCG1蛋白表达均降低(P<0.05,P<0.01);与模型组比较,阿托伐他汀组和总黄酮中、高剂量组上述指标均有改善(P<0.05,P<0.01)。结论芳香新塔花总黄酮可抑制ApoE^(-/-)动脉粥样硬化小鼠肝脏脂质代谢水平,其机制可能与激活PPARγ/LXRα/ABCA1通路有关。AIM To explore the effects of total flavonoids of Ziziphora bungeana Juz.on liver lipid metabolism and PPARγ/LXRα/ABCA1 pathway in ApoE^(-/-)mouse model of atherosclerosis.METHODS 60 ApoE^(-/-)mice given 8 weeks feeding of high-fat diet were randomly divided into the model group,the atorvastatin group(3 mg/kg),and the low-dose,medium-dose and high-dose groups(25,50,100 mg/kg)of total flavonoids of Z.bungeana,with 12 mice in each group for corresponding administration of drugs by gavage and simultaneous high-fat diet feeding for 12 weeks.Additionally,12 C57BL/6J mice of the blank group were given normal saline by gavage and normal feeding.After the administration,the mice had their hepatic lipid deposition observed by oil red O staining;their morphology of aortic plaque observed by HE staining;their blood lipid level detected by automatic biochemical analyzer;their serum levels of IL-18,IL-1βand MCP-1 detected by ELISA;their hepatic levels of TC,TG,NEFA and FC detected by kit,and their hepatic protein expressions of PPARγ,LXRα,ABCA1 and ABCG1 detected by Western blot.RESULTS Compared with the blank group,the model group displayed increased ABCA1 of liver lipid droplets(P<0.01);increased serum levels of TC,TG,LXRα-C,IL-18,IL-1β,MCP-1 and hepatic levels of TC,TG,NEFA and FC(P<0.05,P<0.01);and increased serum HDL-C level and hepatic protein expressions of PPARγ,LXRα,ABCA1,ABCG1(P<0.05,P<0.01).Compared with the model group,atorvastatin group and the medium-dose and high-dose groups of total flavonoids of Z.bungeana shared improvements in terms of the aforementioned indices levels(P<0.05,P<0.01).CONCLUSION The total flavonoids of Z.bungeana can inhibit the liver lipid metabolism level in ApoE^(-/-)mouse model of atherosclerosis,and its mechanism may be related to the activation of PPARγ/LXRα/ABCA1 pathway.

关 键 词：芳香新塔花总黄酮 ApoE^(-/-)小鼠 动脉粥样硬化 肝脏脂质代谢 PPARγ/LXRα/ABCA1通路 

分 类 号：R285[医药卫生—中药学]