蛹虫草多糖促进CETP-tg小鼠胆固醇逆转运  

Cordyceps militaris polysaccharide promotes reverse cholesterol trans⁃port in CETP-tg mice

作　　者：邵波 李英 王效琰 翟晓天 田华 刘伯言 张颖 司艳红 秦树存 SHAO Bo;LI Ying;WANG Xiao-yan;ZHAI Xiao-tian;TIAN Hua;LIU Bo-yan;ZHANG Ying;SI Yan-hong;QIN Shu-cun(College of Basic Medical Sciences,Shandong First Medical Uni-versity,Taian 271000,China;Institute of Atherosclerosis,Shandong First Medical Uni-versity,Taian 271000,China;The Second Clinical College,Shandong First Medical Uni-versity,Taian 271000,China)

机构地区：[1]山东第一医科大学基础医学院,山东泰安271000 [2]山东第一医科大学动脉粥样硬化研究所,山东泰安271000 [3]山东第一医科大学第二临床学院,山东泰安271000

出　　处：《中国病理生理杂志》2020年第10期1754-1760,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81600681,No.81800394);山东省泰山学者岗位专项科研基金(No.ts201511057);山东省重点研发计划项目(No.2019GSF108260)。

摘　　要：目的:本研究验证蛹虫草多糖(CMPS)在体内外促进胆固醇逆向转运(RCT)的效应,并探讨相关机制。方法:采用CETP-tg小鼠作为动物模型,通过同位素示踪技术检测体内的RCT效率;酶法测定血浆脂质水平。采用RAW264.7巨噬细胞源性泡沫细胞作为细胞模型,油红O染色和总胆固醇试剂盒检测泡沫细胞胆固醇外排后剩余脂质含量。Western blot分析泡沫细胞及小鼠肝脏内涉及胆固醇转运、摄取、转化的相关蛋白水平。结果:CMPS灌胃4周后,高脂饮食CETP-tg小鼠血浆总胆固醇(TC)、低密度脂蛋白胆固醇及高密度脂蛋白胆固醇浓度分别降低24%、23%和22%,体内RCT过程加速,血浆、胆汁、肠道及粪便外排通路中3H-胆固醇放射活性明显升高,同时,肝脏中胆固醇受体SR-B1和LDLR及转化酶CYP7A1蛋白表达上调,分别增加了105%、71%和58%。体外实验显示:CMPS促进了巨噬细胞源性泡沫细胞胆固醇外排,细胞内脂质和TC水平明显降低,同时,上调了巨噬细胞PPARγ-LXRα-ABCA1/ABCG1信号通路相关蛋白的表达。结论:CMPS促进了外周巨噬细胞中多余胆固醇的流出和体内胆固醇经肝脏途径外排,其机制可能与PPARγ-LXRα-ABCA1/ABCG1通路激活有关。AIM:To verify whether Cordyceps militaris polysaccharide(CMPS)has the effect of promoting re⁃verse cholesterol transport(RCT)in vitro and in vivo,and to explore the underlying mechanism.METHODS:For in vivo experiments,RCT efficiency was detected in cholesterol ester transporter transgene(CETP-tg)mice by isotope tracer tech⁃nique,and the plasma lipid levels were measured by enzyme method.For in vitro experiments,the residual lipid content after cholesterol efflux in RAW264.7 macrophage-derived foam cells was tested by oil red O staining and total cholesterol(TC)kit.Western blot was used to analyze the protein expression of the molecules involved in cholesterol transport,up⁃take and transformation in the foam cells and mice liver.RESULTS:After 4 weeks of intragastric administration of CMPS,the concentrations of TC,low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)in the plasma of CETP-tg mice were reduced by 24%,23%and 22%,respectively.RCT efficiency of CETP-tg mice was accelerated and the appearance of 3H-cholesterol tracer in plasma,bile,intestine and feces was significantly in⁃creased in CMPS group.Meanwhile,the expression levels of cholesterol receptors scavenger receptor B1(SR-B1)and LDL receptor(LDLR),and cholesterol converting rate-limiting enzyme cholesterol 7α-hydroxylase A1(CYP7A1)were upregulated by 105%,71%and 58%in the liver of CMPS group,respectively.The results of in vitro experiments showed that CMPS preincubation promoted cholesterol efflux,decreased intracellular lipid and TC levels,and up-regulated the ex⁃pression of peroxisome proliferator-activated receptorγ(PPARγ)-liver X receptorα(LXRα)-ATP-binding cassette trans⁃porter A1(ABCA1)/ABCG1 signaling pathway related proteins in macrophage-derived foam cells.CONCLUSION:CMPS promotes excess cholesterol efflux from peripheral macrophage-derived foam cells and accelerates its discharge through liver pathway.PPARγ-LXRα-ABCA1/ABCG1 pathway may be involved in the mechanism.

关 键 词：蛹虫草多糖 胆固醇逆转运 动脉粥样硬化 巨噬细胞源性泡沫细胞 PPARγ-LXRα-ABCA1/ABCG1信号通路 

分 类 号：R543.2[医药卫生—心血管疾病] R363.2[医药卫生—内科学]