四君子汤对快速衰老型小鼠海马及肝脏ABCA1蛋白表达的影响  

Effects of ABCA1 protein expression in hippocampus and liver of rapidly aging mice by Sijunzi Decoction

作　　者：刘旭东[1] 王松楠 马丹[1] 刘文俊[1] 马丽娜[1] 冷雪[1] 赵丹玉[1] 任路[1] LIU Xudong;WANG Songnan;MA Dan;LIU Wenjun;MA Lina;LENG Xue;ZHAO Danyu;REN Lu(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：《中华中医药杂志》2024年第12期6735-6739,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：辽宁省科学技术计划省自然科学基金指导计划(No.201601192);辽宁省教育厅科学技术研究基础研究项目(No.L202006);国家自然科学基金青年科学基金项目(No.81803854);辽宁中医药大学中西医结合学院2023年“岐济”人才支撑计划项目(No.2023QJ 02002)。

摘　　要：目的:研究快速衰老小鼠海马及肝脏三磷酸腺苷结合盒A1转运蛋白(ABCA1)转运胆固醇表达变化,为健脾益气法治疗阿尔茨海默病(AD)提供理论依据。方法:8只3月龄SAMR1小鼠作为正常组,32只3月龄SAPM8小鼠分为模型组、西药组、低剂量组、高剂量组,每组8只。西药组灌胃多奈哌齐(0.013 mg/mL),低、高剂量组灌胃相应剂量的四君子汤(3.59、28.72 mg/mL)。水迷宫检测小鼠认知功能;免疫组化法检测肝脂肪酸合成酶(FASN)蛋白及海马载脂蛋白E(APOE)表达变化,ELISA法检测血浆中总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇含量,Western Blot法检测肝脏组织浮舰蛋白1(flotillin-1)、ABCA1、低密度脂蛋白受体(LDLR)蛋白及海马组织flotillin-1、ABCA1、APOE蛋白表达变化。结果:与正常组比较,模型组小鼠逃避潜伏时间显著增加、平台穿越次数显著减少(P<0.01);血清总胆固醇含量显著升高、高密度脂蛋白胆固醇含量显著降低(P<0.01);肝脏FASN蛋白及海马APOE蛋白表达显著升高(P<0.01);肝脏flotillin-1蛋白、ABCA1、LDLR蛋白表达显著升高(P<0.01),海马flotillin-1、APOE蛋白表达显著升高(P<0.01),ABCA1蛋白表达显著降低(P<0.01)。与模型组比较,低、高剂量组小鼠逃避潜伏时间显著减少、平台穿越次数显著增加(P<0.05);血清总胆固醇含量显著降低、高密度脂蛋白胆固醇含量显著升高(P<0.01);肝脏FASN、LDLR及海马APOE蛋白表达显著降低(P<0.01),其中高剂量组ABCA1蛋白表达显著降低(P<0.01);海马flotillin-1、APOE蛋白表达显著降低(P<0.01),ABCA1蛋白表达显著升高(P<0.01)。结论:四君子汤可以提高SAMP8小鼠的记忆功能,治疗AD,其机制可能是通过调节肝脏和海马ABCA1蛋白功能,纠正中枢和外周胆固醇转运紊乱有关。Objective:To study the changes in the expression of ATP-binding cassette transporter A1(ABCA1)proteintransported cholesterol in the hippocampus and liver of rapidly aging mice,and to provide a theoretical basis for the treatment of Alzheimer’s disease(AD)by strengthening the spleen and benefiting the qi method.Methods:Eight three months-old SAMR1 mice were used as the normal group,and 32 three months-old SAPM8 mice were divided into model group,western medicine group,low-dose group and high-dose group,8 mice in each group,and the western medicine group was gavaged with Donepezil(0.013 mg/mL),while the low-dose group and the high-dose group were gavaged with Sijunzi Decoction(3.59,28.72 mg/mL).The mice were tested for memory in the Morris water maze;the changes in the expression of fatty acid synthase(FASN)in the liver and apolipoprotein E(APOE)in the hippocampus were detected by immunohistochemistry,the total cholesterol,high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the plasma were detected by ELISA.The expression changes of flotillin-1,ABCA1,LDLR protein in the liver and flotillin-1,ABCA1 and APOE protein in the hippocampus were detected by Western Blot.Results:Compared with the normal group,the mice in the model group significantly increased latent escape time and significantly decreased crossing times(P<0.01);serum total cholesterol significantly increased and HDL cholesterol significantly decreased(P<0.01);hepatic FASN protein expression and hippocampal APOE protein expression increased(P<0.01);expression of liver flotillin-1 protein,ABCA1 and LDLR protein significantly increased(P<0.01),expression of hippocampal flotillin-1 and APOE protein significantly increased(P<0.01),and expression of ABCA1 protein significantly decreased(P<0.01).Compared with the model group,the low-and high-dose groups significantly decreased latent escape time and significantly increased crossing times(P<0.05),serum total cholesterol significantly increased and HDL cholesterol significantly increas

关 键 词：四君子汤 阿尔茨海默病 胆固醇 三磷酸腺苷结合盒A1转运蛋白 机制 转运 脂肪酸合成酶 载脂蛋白E 

分 类 号：R28[医药卫生—中药学]