基于Apoa-Ⅰ调控胆固醇逆向转运探讨磷脂酰胆碱对高脂血症小鼠的影响  

Based on the regulation of cholesterol reverse transport by Apoa-Ⅰ,to explore the effect of phosphatidylcholine on hyperlipidemic mice

作　　者：张琦[1] 隋国媛 宋囡[1] 贾连群[1] ZHANG Qi;SUI Guoyuan;SONG Nan;JIA Lianqun(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学,沈阳110847

出　　处：《中国实验动物学报》2025年第1期23-33,共11页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金资助项目(82374423,82074145,81974548);辽宁省高校黄大年式教师团队,辽宁省教育厅高校基本科研项目(LJ232410162027)。

摘　　要：目的基于载脂蛋白a-I(apolipoprotein a-I,Apoa-I)基因敲除小鼠探究磷脂酰胆碱(phosphotidylcholine,PC)改善胆固醇逆向转运的作用及机制。方法采用随机数字表法将30只Apoa-I^(-/-)小鼠分为Apoa-I^(-/-)组、Apoa-I^(-/-)+HFD组、Apoa-I^(-/-)+HFD+PC组;30只C57BL/6J小鼠作为对照分为WT组、WT+HFD组、WT+HFD+PC组,每组10只。Apoa-I^(-/-)组和WT组给予基础饲料饲喂,其余组给予高脂饲料饲喂8周建立高脂血症模型。于第9周开始,Apoa-I^(-/-)+HFD+PC组及WT+HFD+PC组给予PC 2.5 g/(kg·d),其余小鼠给予生理盐水灌胃,共干预4周。全自动分析仪检测小鼠血清血脂水平,苏木素-伊红(HE)染色及油红O染色观察小鼠肝组织病理形态学变化,COD-PAP法检测小鼠肝组织中胆固醇水平,ELISA法检测小鼠血清中卵磷脂胆固醇酰基转移酶(lecithin cholesterol acyltransferase,LCAT)水平,RT-qPCR法及Western Blot检测肝组织中ATP结合盒转运子A1(ATP-binding cassette transporter A1,ABCA1)、ATP结合盒转运子G1(ATP-binding cassette transporter G1,ABCG1)、LCAT、肝酯酶(hepatic lipase,HL)、B类Ⅰ型清道夫受体(scavenger receptor class B type 1,SR-B1)及低密度脂蛋白胆固醇受体(low density lipoprotein receptor,LDL-R)mRNA及蛋白表达。结果与WT组比较,WT+HFD组小鼠血清中血脂水平显著升高(P<0.01),LCAT水平显著降低(P<0.05),肝细胞脂肪空泡明显,肝脂质沉积显著,肝组织中TC水平显著升高(P<0.01),ABCA1、ABCG1、LCAT、SR-B1、HL及LDL-R mRNA及蛋白表达显著降低(P<0.05,P<0.01)。与WT+HFD组比较,WT+HFD+PC组小鼠血清中血脂水平显著降低(P<0.05,P<0.01),LCAT水平显著升高(P<0.05),肝细胞脂肪空泡显著减少,肝脂质沉积减轻,肝组织中TC水平显著减低(P<0.05),ABCA1、LCAT、SR-B1、HL及LDL-R mRNA及蛋白表达显著升高(P<0.05,P<0.01);Apoa-I^(-/-)+HFD组小鼠血清中TC、TG、LDL-C水平显著升高,LCAT、HDL-C水平显著降低(P<0.05,P<0.01),肝细胞发生气球样变,肝脂质沉积显著加�Objective Based on apolipoprotein a-I(Apoa-I)gene knockout mice,the role and mechanism of phosphotidylcholine(PC)in improving cholesterol reverse transport were explored.Methods Thirty Apoa-I^(-/-)mice were randomly divided into an Apoa-I^(-/-)group,Apoa-I^(-/-)+HFD group,and Apoa-I^(-/-)+HFD+PC group using the random number table method;30 C57BL/6J mice were randomly divided into a WT group,WT+HFD group,and WT+HFD+PC control groups,with 10 mice in each group.The Apoa-I^(-/-)group and WT groups were fed basic feed,while the other groups were fed high-fat feed for 8 weeks to establish a hyperlipidemia model.From the 9th week,the WT+HFD+PC group and Apoa-I^(-/-)+HFD+PC group were given PC 2.5 g/(kg·d),while the remaining mice were given physiological saline by gavage for a total of 4 weeks of intervention.The serum lipid levels of the mice were detected using a fully automated analyzer.Hematoxylin and eosin and Oil red O staining were used to observe pathological and morphological changes,and the COD-PAP method was used to detect cholesterol levels in mouse liver tissue.The ELISA method was used to detect LCTA levels in mouse serum,and RT-qPCR and Western Blot method were used to detect the mRNA and protein expression of cholesterol ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABCA1),lecithin cholesterol acyltransferase(LCAT),hepatic lipase(HL),scavenger receptor class B type I(SR-B1),and low-density lipoprotein receptor(LDL-R)in liver tissue.Results Compared with the WT group,the serum lipid levelsof WT+HFD group mice were significantly increased(P<0.01),LCAT levels were significantly reduced(P<0.05),hepatic fat vacuoles were obvious,hepatic lipid deposition was significant,and liver tissue TC levels were significantly increased(P<0.01).The mRNA and protein expression of ABCA1,ABCG1,LCAT,SR-B1,HL,and LDL-R were significantly reduced(P<0.05,P<0.01).Compared with the WT+HFD group,serum lipid levels in the WT+HFD+PC group were significantly reduced(P<0.05,P<0.01),LCAT levels were si

关 键 词：载脂蛋白A-I 磷脂酰胆碱 胆固醇逆向转运 血脂异常 小鼠 

分 类 号：Q95-33[生物学—动物学]