丁苯酞对阿尔茨海默病模型大鼠海马CA1区Wnt3a及β-连环蛋白表达的影响  

The effects of dl⁃3⁃n⁃butylphthalidle on the expression of Wnt3a and β⁃catenin in CA1 region of hippocampus of rats with Alzheimer disease

作　　者：邓春颖 李海滨[2] 毛文静 李世英 刘斌 DENG Chunying;LI Haibin;MAO Wenjing;LI Shiying;LIU Bin(Neurology,The Affiliated Hospital of North China University of Science and Technology,Tangshan,Hebei 063000,China;Internal Medicine-Cardiovascular Department,People’s Hospital of Zunhua,Zunhua,Hebei 064200,China)

机构地区：[1]华北理工大学附属医院神经内科,河北唐山063000 [2]遵化市人民医院心内科,河北遵化064200

出　　处：《安徽医药》2020年第9期1701-1704,I0001,共5页Anhui Medical and Pharmaceutical Journal

基　　金：河北省重点研发计划自筹项目(172777151);华北理工大学科学研究基金项目(Z201734)。

摘　　要：目的观察丁苯酞(dl-3-n-butylphthalidle)软胶囊对阿尔茨海默病(Alzheimer disease,AD)模型大鼠海马CA1区Wnt3a蛋白及β-连环蛋白(β-catenin)表达的影响,探寻丁苯酞发挥脑保护作用的可能机制。方法将72只雄性SD大鼠按随机数字表法分为假手术组(Sham组)、AD模型组(AD组)、丁苯酞治疗组(丁苯酞组)。向双侧海马区注射β-淀粉样蛋白1-42(beta-amyloid people 1-42,Aβ1-42)制作AD模型,Sham组注射5μL 0.9%氯化钠溶液。造模成功后4周,丁苯酞组给予丁苯酞与食用油混合后制成的丁苯酞混合溶液灌胃;Sham组和AD组采用同等剂量的食用油进行灌胃。采用免疫组织化学法和蛋白质印迹法分别于给药后1、2、4和8周检测海马CA1区Wnt3a及β-catenin表达情况。结果蛋白质印迹法表明与Sham组给药后1、2、4和8周[(3 845.25±52.35),(4 385.06±108.85),(9 392.19±81.07),(6 833.15±76.03)]相比,AD组各时间点Wnt3a蛋白表达量增多[(5 595.54±94.60),(7 223.89±86.73),(13 671.83±312.38),(11 641.04±203.65),均P<0.01];各时间点β-catenin蛋白表达量差异无统计学意义(P>0.05)。与AD组[(4 132.90±79.63),(4 758.74±155.14),(5 188.92±111.82),(5 912.07±83.26)]相比,丁苯酞组各时间点Wnt3a蛋白[(6 261.26±206.51),(8 427.83±293.61),(16 469.74±204.55),(13 438.21±12 399.19)]、β-catenin蛋白表达量明显增多[(5 569.53±96.52),(7 127.78±69.64),(11 454.94±396.43),(9 937.91±157.87),均P<0.01]。免疫组织化学法和蛋白质印迹法检测结果相同。结论丁苯酞可通过上调Wnt3a及β-catenin蛋白的表达,发挥对AD模型大鼠的脑保护作用。Objetive Assessed the effects of Dl⁃3⁃n⁃butylphthalidle on the expression of Wnt3a andβ⁃catenin in CA1 region of hip⁃pocampus of rats with Alzheimer disease,explored the mechanism of brain protection by butylphthalide.Methods 72 SD rats were randomly divided into the sham⁃operation group,the Alzheimer disease model group(AD group)and the NBP treated group(NBP group).The Alzheimer disease rat model was prepared by injecting beta⁃amyloid people 1⁃42 into bilateral hippocampus.Four weeks after the model was successfully established,the NBP group was given the mixture solution of NBP and edible oil by gavage,while the Sham group and AD group were given the same dose of edible oil by gavage.The expressions of Wnt3a andβ⁃catenin in the hip⁃pocampal CA1 region were detected at 1,2,4 and 8 weeks after administration by immunohistochemistry and Western blotting.Results Western blotting showed that compared with the results of 1,2,4,and 8 weeks after taking medicines in the sham⁃opera⁃tion group which were[(3845.25±52.35),(4385.06±108.85),(9392.19±81.07),(6833.15±76.03)],the expression of Wnt3a protein increased in AD group at each time points[(5595.54±94.60),(7223.89±86.73),(13671.83±312.38),(11641.04±203.65)],the data differences were statistically significant(P<0.01).The data difference of the expression ofβ⁃catenin in the two groups was not statistically significant(P>0.05).Compared with the AD group[(4132.90±79.63),(4758.74±155.14),(5188.92±111.82),(5912.07±83.26)],the expression of Wnt3a protein[(6261.26±206.51),(8427.83±293.61),(16469.74±204.55),(13438.21±12399.19)]andβ⁃catenin[(5569.53±96.52),(7127.78±69.64),(11454.94±396.43),(9937.91±157.87)]both in⁃creased in NBP group at each time points,the data differences were statistically significant(all P<0.01).The results of immunohis⁃tochemistry and western blotting were the same.Conclusion NBP can protect the brain of AD model rats by up⁃regulating the expression of Wnt3a and⁃catenin protein.

关 键 词：阿尔茨海默病 海马 丁苯酞 Wnt3a蛋白 Β-连环蛋白 大鼠 SPRAGUE-DAWLEY 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]