摘要
目的探讨姜黄素对9月龄AD小鼠海马CA1区β淀粉样蛋白(Aβ)生成酶早老素2(PS2)及降解酶胰岛素降解酶(IDE)和脑啡肽酶(NEP)的持续影响。方法将3月龄APP/PS1双转基因小鼠随机分为模型组、罗格列酮组(10 mg/kg)和姜黄素高、中、低(400、200、100 mg/kg)剂量组,同窝非转基因C57/BL6J小鼠作为对照组,连续灌胃6个月,应用免疫组织化学和Western-blot检测Aβ生成酶PS2、Aβ降解酶IDE和NEP的表达。结果与对照组相比,模型组Aβ生成酶PS2表达增加(P<0.01);与模型组相比,各干预组小鼠海马Aβ生成酶PS2表达减少(P<0.01或P<0.05),海马CA1区PS2阳性细胞减少(P<0.05)。与对照组相比,模型组Aβ降解酶IDE和NEP表达显著减少(P<0.01);与模型组相比,各干预组小鼠海马Aβ降解酶IDE和NEP表达增加(P<0.01或P<0.05),海马CA1区IDE和NEP阳性细胞增加(P<0.01或P<0.05)。结论增加AD模型小鼠海马Aβ降解酶IDE和NEP的表达,减少Aβ生成酶PS2的表达,是姜黄素减少Aβ沉积的作用机制之一。
Objective To explore the sustainable effects of curcumin on presenilin 2 （PS2）, β-amyloid （Aβ） generation enzyme, and insulin degrading enzyme （IDE） and neprilysin （NEP）, Aβ degrading enzymes, in hippocampal CA1 region of 9-month-old Alzheimer＇ s disease （AD）mice. Methods The 3- month-old APP/PS1 double transgenic mice were randomly divided into model group, rosiglitazone group, curcumin high-dose, mid-dose and low-dose group at dose of 400, 200, 100 mg/kg, with littermate non-transgenic mice involved in the control group. After intragastrical administration medicines for consecutive six months, expressions of PS2, IDE and NEP were detected using imunohistochemistry and Western-blot methods. Results Compared with the control group, expression of PS2 increased in the model group significantly （ P 〈 0.01 ）, and compared with the model group, expression of PS2 decreased in all the intervention groups （ P 〈 0.01 or P 〈 0.05 ） with PS2-positive ceils in hippocampus CA1 region decreasing （P 〈 0.05 ）. Compared with the control group, expressions of IDE and NEP decreased significantly in the model group （P 〈 0.01 ） ; compared with the model group, expressions of IDE and NEP increased significantly in all the intervention groups with IDE and NEP-positive cells in hippocampus CA1 region increasing （ P 〈 0.01 or P 〈 0.05 ）. Conclusion It is suggested that one of potential mechanisms of curcumin reducing Aβ accumulation may be via increasing Aβ-degrading enzyme IDE and NEP expression and reducing Aβ-generating enzyme PS2 expression.
出处
《北京中医药大学学报》
CAS
CSCD
北大核心
2016年第3期230-234,共5页
Journal of Beijing University of Traditional Chinese Medicine
基金
国家自然科学基金面上资助项目(No.81073076)
教育部高等学校创新团队(No.IRT0810)
