姜黄素对APP/PS1双转基因小鼠Aβ及Aβ寡聚体表达的影响  

Influences of curcumin on expressions of amyloid β-protein and amyloid β oligomers in APP/PS1 double transgenic mice

作　　者：魏鹏[1,2] 李瑞晟[3] 王虹[4] 任映[1,2] 孙海芸[1,2] 杨金铎[1,2] 王蓬文[1,2] 

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学教育部重点实验室 [3]新疆医科大学第二附属医院 [4]北京美中宜和妇儿医院

出　　处：《北京中医药大学学报》2012年第6期386-390,I0002,共6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);北京市自然科学基金面上资助项目(No.7092057);教育部高等学校创新团队资助项目(No.IRT0810)

摘　　要：目的运用免疫组织化学方法和蛋白质印迹(Western-blot)方法观察淀粉样前体蛋白/早老素1(APP/PS1)双转基因小鼠治疗前后β淀粉样蛋白42(Aβ42)、β淀粉样蛋白40(Aβ40)和可溶性Aβ寡聚体(ADDLs)的变化,判断姜黄素(curcumin)对Aβ级联反应的影响。方法将3月龄的APP/PS1双转基因小鼠随机分为模型组、阳性对照组(罗格列酮组)及姜黄素大、中、小剂量组。灌胃3个月后,以免疫组织化学方法和Western blot方法检测Aβ42、Aβ40和ADDLs蛋白表达量的变化。结果免疫组织化学检测模型组小鼠海马Aβ40、Aβ42和ADDLs阳性细胞均较正常组增加,Aβ40和Aβ42相比,阳性细胞计数增加以Aβ42更加明显,各干预组小鼠海马Aβ40、Aβ42和ADDLs阳性细胞明显降低。Western blot检测模型组小鼠海马Aβ40、Aβ42和ADDLs蛋白表达比正常对照组明显增加(P<0.01);与模型组小鼠相比,虽然各干预组小鼠海马Aβ40、Aβ42和ADDLs蛋白表达均减少,罗格列酮组和姜黄素中剂量组小鼠海马Aβ40和Aβ42的蛋白表达显著减低(P<0.01);罗格列酮组小鼠海马ADDLs的蛋白表达减低显著(P<0.01),姜黄素大、中剂量组小鼠海马ADDLs的蛋白表达明显降低(P<0.05)。结论姜黄素给药3个月能显著减少APP/PS1双转基因小鼠脑内海马CA1区Aβ40、Aβ42和ADDLs的表达,对Aβ42减低更为明显。其潜在的神经保护机制是否通过下调Aβ42和ADDLs的产生,增强Aβ42和ADDLs的降解影响Aβ级联反应,有待进一步研究。Objective To observe the changes of amyloid β-protein 42 （Aβ42）, amyloid β-protein 40 （Aβ40） and amyloid beta-derived diffusible ligands （ADDLs） by applying immunohistochemistry technique and Western blot method in APP/PS1 double transgenic mice before and after treatment with curcumin （Cur） , and review the influence of Cur on Aβ cascade reactions. Methods APP/PS1 double transgenic mice （3 months old） were randomly divided into model group, rosiglitazone group, normal group, and high-dose, mid-dose and low-dose Cur groups （high-dose group, mid-dose group and low-dose group ）. After intragastrical administration of Cur for 3 months, the changes of protein expressions of Aβ42, Aβ40 and ADDLs were detected by using immunohistochemistry technique and Western blot method. Results The detection of immunohistochemistry showed that the positive cells of Aβ42, Aβ40 and ADDLs in hippocampus increased in model group compared with normal group. The comparison between Aβ42 and Aβ40 showed that the increase of positive ceils of A^42 was more significant. The positive cells of Aβ42, Aβ40 and ADDLs in hippoeampus decreased significantly in all intervened groups. The detection of Western blot method showed that the protein expressions of Aβ42, Aβ40 and ADDLs increased significantly in model group compared with normal group （ P 〈 0.01）. Compared with model group, the protein expressions of Aβ42 and Aβ40 decreased significantly in rosiglitazone group and mid-dose group （ P 〈 0.01 ） although they decreased in all intervened groups. The protein expression of ADDI.s decreased significantly in rosiglitazone group （ P 〈 0.01 ） and in high-dose group and mid-dose group （P 〈 0.05 ）. Conclusion Cur, after administration for 3 months, can reduce significantly the expressions of Aβ42, Aβ40 （especially Aβ42） and ADDLs in hippocampus CA1 zone in APP/PS1 double transgenic mice. It depends on further studies whether the neuroprotective mechanism of Cur is due to down-regul

关 键 词：姜黄素 淀粉样前体蛋白/早老素1双转基因 β-淀粉样蛋白42 β-淀粉样蛋白40 可溶性Aβ寡聚体 小鼠 

分 类 号：R285.5[医药卫生—中药学]