糖肾方激活PGC-1α/LXR/ABCA1信号通路改善高脂诱导的巨噬细胞胆固醇摄取及流出  

Tangshen formula improves cholesterol uptake and efflux of macrophages induced by high lipid via activating PGC-1α/LXR/ABCA1 pathway

作　　者：许可 高骏伟 刘鹏 申正日 贾慧 吴宸广 田锋 王立范 李平[3] XU Ke;GAO Junwei;LIU Peng;SHEN Zhengri;JIA Hui;WU Chenguang;TIAN Feng;WANG Lifan;LI Ping(Heilongjiang Academy of Chinese Medicine Sciences,Harbin 150000,Heilongjiang,China;Shunyi Hospital,Beijing Traditional Chinese Medicine Hospital,Beijing 101300,China;Beijing Key Lab Immune-mediated Inflammatory Diseases,Institute of Clinical Medical Sciences,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]黑龙江省中医药科学院,黑龙江哈尔滨150000 [2]北京中医医院顺义医院,北京101300 [3]中日友好医院临床医学研究所,免疫炎性疾病北京市重点实验室,北京100029

出　　处：《中国临床药理学与治疗学》2021年第9期978-985,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金青年项目(8190152536);国家自然科学基金国际(地区)合作与交流项目(81620108031)。

摘　　要：目的:观察中药糖肾方对棕榈酸钠诱导的RAW264.7巨噬细胞的脂质流出、摄取等转运相关分子的影响。方法:用棕榈酸钠(PA)诱导RAW264.7巨噬细胞制造高脂环境,经MTT测定后给予不同浓度糖肾方及PGC-1α-siRNA干预;利用Western blot和Real-time PCR检测细胞过氧化物酶体增殖激活受体γ共激活因子1α(PGC-1α)、肝脏X受体(LXR)、ATP-结合盒转运蛋白(ABCA1)、分化簇36(CD36)的表达;Filipin染色及BODIPY 493/503染色观察糖肾方对细胞内脂滴沉积的影响。结果:Western blot及Real-time PCR的结果提示PA组PGC-1α、LXR、ABCA1表达减少,CD36表达增加(P<0.05),给予糖肾方干预可上调PGC-1α、LXR、ABCA1的表达,下调CD36的表达(P<0.05);Filipin染色及BODIPY 493/503染色结果显示糖肾方可改善高脂状态下细胞内脂滴沉积的情况。PGC-1α-siRNA干预可抑制糖肾方上调PGC-1α、LXR、ABCA1表达以及抑制CD36的表达的作用。结论:糖肾方可激活PGC-1α/LXR/ABCA1信号通路促进脂质流出、下调CD36的表达抑制脂质摄取,改善因脂质代谢异常引起的相关疾病等。AIM:To observe the effects of Tangshen formula(TSF)treatment on lipid efflux and uptake in sodium palmitate(PA)induced RAW264.7 macrophages.METHODS:After 200μmol/L PA induced RAW264.7 macrophages,TSF and PGC-1α-siRNA were given to intervene respectively.The lipid content in the cells was detected by ELISA kit;intracellular lipid droplet deposition was detected by BODIPY 493/503 and Filipin staining.Western blot and Real-time PCR were used to detect the expression of PGC-1α,LXR,ABCA1 and CD36.RESULTS:TSF diminished the levels of TC,TG and intracellular lipid droplet deposition in PA-induced RAW264.7 macrophages.Western blot and Real-time PCR analysis showed that TSF could up-regulate the expression of PGC-1α,LXR,ABCA1 and down-regulate the expression of CD36.Furthermore,silencing PCG-1αby SiRNA significantly suppressed the effects of upregulating the expression of PGC-1α,LXR and ABCA1,and downregulating the CD36 expression with TSF treatment.CONCLUSION:TSF may extenuate intracellular lipid droplet deposition in macrophages by upregulating cholesterol efflux through activating the PGC-1α/LXR/ABCA1 pathway and inhibiting lipid uptake through down-regulateing the expression of CD36.

关 键 词：糖肾方 高脂血症 PGC-1α/LXR/ABCA1通路 CD36 

分 类 号：R965.2[医药卫生—药理学]