【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。更多还原

【Abstract】 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 SAMR1mice 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 increased(P<0.01); hepatic FASN, LDLR protein expression and hippocampal APOE protein expression significantly decreased(P<0.01),and ABCA1 protein expression in the high dose group decreased(P<0.01); hippocampal flotillin-1 and APOE protein protein expression significantly decreased(P<0.01) and ABCA1 protein expression significantly increased(P<0.01). Conclusion: Sijunzi Decoction can improve the memory function of SAMP8 mice and treat AD, and the mechanism may be related to the correction of central and peripheral cholesterol transport disorder by regulating the function of ABCA1 protein in the liver and hippocampus.更多还原