基于FXR/SHP信号通路探讨芩连红曲汤改善高脂血症大鼠肝脂肪变性的机制研究  

Mechanism of Qinlian Hongqu Decoction(芩连红曲汤)in Alleviation of Liver Steatosis in Rats with Hyperlipidemia Based on FXH/SHP Signaling Pathway

作　　者：张永[1] 张小波 郭志清[2] 刘峻呈 杨炀[4] 陈东辉[4] 罗雅琪[4] Zhang Yong;Zhang Xiaobo;Guo Zhiqing;Liu Juncheng;Yang Yang;Chen Donghui;Luo Yaqi(College of Basic Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu 611137;Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072;Pengzhou Hospital of Traditional Chinese Medicine,Pengzhou 611930;Sichuan Institute of Traditional Chinese Medicine/Sichuan Second Hospital of Traditional Chinese Medicine,Chengdu 610031)

机构地区：[1]成都中医药大学基础医学院,成都611137 [2]成都中医药大学附属医院,成都610072 [3]彭州市中医医院,彭州611930 [4]四川省中医药科学院中医研究所(四川省第二中医医院),成都610031

出　　处：《中药药理与临床》2022年第5期16-20,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：四川省科技厅省级科研院所基本科研业务费项目(编号:2022JDKY0029)。

摘　　要：目的:探讨芩连红曲汤改善高脂血症大鼠肝脂肪变性的作用机制。方法:雄性SD大鼠40只,随机分为正常对照组、模型对照组、芩连红曲汤0.7、1.4、2.8 g/kg组,每组8只。正常对照组给予基础饲料喂养,其余各组给予D12451高脂饲料喂养,制备高脂血症大鼠模型。造模成功后各造模组给予相应药物灌胃,正常对照组和模型对照组给予等体积的生理盐水灌胃,1次/d,连续给药8 w。采用全自动生化仪检测血清中胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量;HE及油红染色观察肝脏病理学变化;ELISA法检测肝脏的TC、TG含量;Western blot法测定肝脏的FXR、SHP、SREBP1-C及PPARα蛋白表达。结果:与正常对照组比较,模型对照组血清TC、TG和LDL-C含量显著升高(P<0.01),肝细胞脂滴明显增多、肝细胞脂肪变性,肝脏TC、TG含量明显升高(P<0.05),肝脏FXR、SHP和PPARα蛋白表达明显下调(P<0.05或P<0.01),SREBP1-C蛋白表达显著上调(P<0.01);与模型对照组比较,芩连红曲汤0.7 g/kg组的血清TC、TG、LDL-C含量显著降低(P<0.01),HDL-C含量显著升高(P<0.01),肝细胞脂滴沉积减少、肝细胞脂肪变性明显改善,肝脏TC、TG含量明显降低(P<0.05),肝脏FXR、SHP和PPARα蛋白表达明显上调(P<0.05或P<0.01),SREBP1-C蛋白表达明显下调(P<0.01)。结论:芩连红曲汤对高脂血症大鼠降脂效果显著,能减轻高脂血症引起的肝细胞脂肪变性,其机制可能与调节肝脏FXR/SHP信号通路,上调肝脏PPARα蛋白表达促进脂肪酸氧化,下调肝脏SREBP1-C蛋白表达抑制肝脏脂肪合成有关。Objective:To investigate the mechanism of Qinlian Hongqu Decoction(芩连红曲汤,QLHQ)in the alleviation of liver steatosis in rats with hyperlipidemia.Methods:Forty male SD rats were randomly divided into 5 groups,namely,a control group,a model group,a 0.7 g/kg QLHQ group,a1.4 g/kg QLHQ group,and a 2.8 g/kg QLHQ group,with 8 rats in each group.The control group was given basal feed,and other groups were given D12451 high-fat diet to induce the rat model of hyperlipidemia.After successfully modeling,rats in each group were administrated with corresponding drugs or equal volume of normal saline by gavage,once a day for 8 weeks.The levels of cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)in the serum were detected by the automatic biochemical instrument.The liver histopathological changes were observed by hematoxylin-eosin(HE)staining and oil red staining.The levels of TC and TG in the liver tissue were determined by enzyme-linked immunosorbent assay(ELISA).The protein expressions of farnesoid X receptor(FXR),small heterodimer partner(SHP),sterol regulatory element binding protein-1 c(SREBP-1 c),and peroxisome proliferator-activated receptorα(PPARα)in the liver tissue were determined by Western blot.Results:As compared with the control group,the content of TG,TC,and LDL-C in the serum was increased(P<0.01)in the model group,the accumulation of lipid droplets in hepatocytes was significantly increased,and steatosis was observed in hepatocytes.The content of TC and TG in the liver tissue was increased(P<0.05)in the model group.The protein expressions of FXR,SHP,and PPARαwere down-regulated(P<0.01,P<0.05),while the protein expression of SREBP-1 c was up-regulated(P<0.01)in the model group.As compared with the model group,the content of TC,TG,and LDL-C in the serum was decreased in the 0.7 g/kg QLHQ group(P<0.01)but the content of HDL-C was increased(P<0.01),and the accumulation of lipid droplets in hepatocytes was reduced,and steatosis w

关 键 词：芩连红曲汤 高脂血症大鼠 法尼醇受体 小异二聚体伴侣 固醇调节元件结合蛋白1 过氧化物酶体增殖激活受体 

分 类 号：R285.5[医药卫生—中药学]