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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 effect of amyloid precursor protein (APP / PS1) double transgenic mice before and after treatment with β-amyloid protein 42 (Aβ42), amyloid β protein 40 (Aβ40) and soluble Aβ oligomers (ADDLs) changes, to determine curcumin Aβ cascade reaction. Methods Three-month-old APP / PS1 double transgenic mice were randomly divided into model group, positive control group (rosiglitazone group) and curcumin large, medium and small dose groups. Three months after gavage, the changes of protein expression of Aβ42, Aβ40 and ADDLs were detected by immunohistochemistry and Western blot. Results Compared with the normal group, the positive cells of Aβ40, Aβ42 and ADDLs in the hippocampus of model group were increased by immunohistochemistry. Compared with Aβ40, the number of positive cells in Aβ40 group was increased and Aβ42 was more obvious. The positive expression of Aβ40, Aβ42 and ADDLs in hippocampus of each intervention group Cells were significantly reduced. The protein expression of Aβ40, Aβ42 and ADDLs in the hippocampus in the model group was significantly higher than that in the normal control group (P <0.01) by Western blot. Compared with the model group, the expression of Aβ40, Aβ42 and ADDLs in the hippocampus (P <0.01). The protein expression of ADDLs in the hippocampus of the rosiglitazone group decreased significantly (P <0.01), and the protein expression of Aβ40 and Aβ42 in the hippocampus of the rosiglitazone group and curcumin middle dose group decreased significantly The protein expression of ADDLs in hippocampus of curcumin large and medium dose groups was significantly decreased (P <0.05). CONCLUSION: Curcumin administration for 3 months can significantly reduce the expression of Aβ40, Aβ42 and ADDLs in hippocampal CA1 region of APP / PS1 double transgenic mice, and decrease the Aβ42 more significantly. Whether its potential mechanism of neuroprotection needs to be further studied by down-regulating the production of Aβ42 and ADDLs, enhancing the degradation of Aβ42 and ADDLs and affecting the Aβ cascade.