四氢姜黄素固体分散体对D-半乳糖联合三氯化铝致小鼠学习记忆障碍的作用研究

Effect of Tetrahydrocurcuminoids on Alzheimer's disease induced by D-galactose and AlCl_3

目的:观察不同剂量的四氢姜黄素(Tetrahydrocurcuminoids,THC)固体分散体对D-半乳糖(D-galactose)联合三氯化铝(AlCl_3)致小鼠实验性阿尔兹海默症(AD)模型的影响及对改善AD的作用机制。方法:采用腹腔注射D-半乳糖联合灌胃三氯化铝造成小鼠AD模型,给药组小鼠分别给予不同剂量的四氢姜黄素固体分散体(20 mg/kg、60 mg/kg、200 mg/kg,连续给药35天)。通过小鼠自主活动实验,观察四氢姜黄素对小鼠中枢神经系统的影响。通过Morris水迷宫观察小鼠学习记忆的改善作用。采用免疫组化法检测小鼠脑组织中β淀粉样蛋白(Aβ)、BACE及PS-1含量的变化。结果:四氢姜黄素固体分散体对小鼠中枢神经系统无影响;水迷宫结果显示,四氢姜黄素固体分散体200 mg/kg能明显缩短小鼠潜伏期,减少运动总距离;四氢姜黄素固体分散体60 mg/kg组能明显缩短小鼠潜伏期。免疫组化显示,四氢姜黄素固体分散体200 mg/kg组可显著降低小鼠脑中的β淀粉样蛋白(Aβ)、PS-1的含量;四氢姜黄素固体分散体20 mg/kg、60 mg/kg组能明显降低小鼠脑中的Aβ与BACE的含量。结论:四氢姜黄素(THC)可改善D-半乳糖联合三氯化铝造模小鼠的学习记忆能力,其机制可能是通过下调BACE和PS-1的异常表达,减少Aβ的生成量。

Objective: To study the effect of Tetrahydrocurcuminoids( THC) on D-galactose( D-galactose) combined with Aluminum chloride( AlCl3) induced experimental Alzheimer’s disease( AD) mice model and its mechanism. Methods: AD mice model was established by injection of D-galactose intraperitoneal combined with intragastric administration of AlCl3 on mice. After models were established,mice were administered with different doses of Tetrahydrocurcuminoids( 20 mg/kg,60 mg/kg and T200 mg/kg) for 35 days constantly. The effect of THC on mice central nervous system was observed in mice autonomous activity experiments. Effect on mice learning and memory was observed through Morris behavior training. The contents of amyloid β protein( Aβ),BACE and PS-1 in the brain tissues of mice were detected by immunohistochemistry. Results: Tetrahydrocurcuminoids had no effect on the central nervous system in mice. Morris water maze result showed THC at the dose of 200 mg/kg significantly shortened the escape period,decreased the total distance of movement. THC at the dose of 60 mg/kg shortened the escape period of mice. Immunohistochemical results showed that THC at the dose of 200 mg/kg significantly reduced the contents of β-amyloid( Aβ) and PS-1,while 60 mg/kg reduced the levels of Aβ and BACE in the brain tissue,THC at the dose of 20 mg/kg significantly reduced the levels of Aβ and BACE in the brain tissue. Conclusion: Tetrahydrocurcuminoids( THC) may improve the ability of learning and memory of D-galactose combined with AlCl3 induced mice model,the mechanism may be related to reducing the production of Aβ by down-regulating the expression of BACE and PS-1.