EGCG对化学诱导AD模型小鼠脑部退行性病变的影响

Research on EGCG Improving the Degenerative Changes of the Brain in AD Model Mice Induced with Chemical Drugs

目的:研究(-)表没食子儿茶素没食子酸酯(epigallocatechin-3-gallate,EGCG)对阿尔茨海默病(AD)模型小鼠的脑部退行性病变的作用及作用机制。方法:给小鼠每日按150 mg/kg皮下注射3%的D-半乳糖(D-galac-tose,D-gal),连续注射42 d,以制备AD小鼠脑部退行性病变模型;造模14 d后每日给EGCG低、高剂量组小鼠按2mg/kg灌胃0.04%或0.12%的EGCG 1次,VE阳性对照组小鼠按280 U/kg灌胃5.6%VE1次,连续给药28 d。通过对各组小鼠脑部HE染色、海马区β-淀粉样肽(Aβ)免疫组化分析及Western blot检测β-淀粉样肽前体蛋白(APP)的蛋白表达水平,观察EGCG对AD模型小鼠脑部病理改变的影响及作用机制。结果:EGCG显著减轻了D-半乳糖诱导的AD模型小鼠海马神经元的损伤,并显著减少了D-半乳糖诱导AD小鼠海马区的Aβ及APP蛋白表达水平(P<0.01)。结论 EGCG可能通过降低D-半乳糖诱导的APP含量的增加及Aβ的毒性作用,发挥对D-半乳糖诱导的AD模型鼠的脑部病理改变的保护作用。

Objective：To study the effect and mechanism of（–）-Epigallocatechin-3-gallate（EGCG） on the degeneretive changes of the brain in Alzheimer′s disease（AD） model mice induced with chemical drugs.Methods：AD model mice were established by subcutaneously injecting with 3% D-gal at the dose of 150 mg/kg body weight once daily for 6 weeks.From the third week,the mice of D-gal ＋ VE 280 U/kg group,D-gal ＋ EGCG 2 mg/（kg·d） group and D-gal ＋ EGCG 6 mg/（kg·d） group were intragastricly given with 5.6%VE at the dose of 280 IU/kg and EGCG at the dose of 2 mg/kg.d or 6 mg/kg.d respectively after injection of D-gal.The mice of control group,D-gal ＋ dd H2O group and D-gal ＋ oil group were administered with same volume vehicle distilled water and soybean oil respectively.The pathological changes of the brain in AD model mice were observed by HE staining analysis,the immunohistochemical analysis of β-amyloid（Aβ） and evaluating the expression of amyloid precursor protein（APP） in the hippocampus of mice by Western blot analysis.Results：EGCG 2 mg/（kg·d） or 6 mg/（kg·d） 4 weeks,ig evidently released neuronal injury in the hippocampus of the AD mice induced by D-gal,and significantly reduced the express of Aβ and APP in the hippocampus of AD model mice induced by D-gal（P0.01）.Conclusion：EGCG has a protective effect on AD model mice induced by D-gal by decreasing the expression of APP and β-Amyloid in the hippocampus of mice.