Objective To observe the effect of tetrahydroxy stilbene glucoside(TSG) on the expressions of caspase-3 and amyloid precursor protein(APP) in brain tissues of APP/presenilin-1(PS1) double transgenic mouse model of Alzheimer′s disease(AD),and to investigate the possible mechanisms of therapeutic effect about TSG on AD.Methods In October 2014,50 SPF rank male APP/PS1 double transgenic mice were randomly divided into model group,huperzine A group and low-dose TSG group,mid-dose TSG group,high-dose TSG group with 10 mice in each based on the random number table.Another 10 SPF rank male C5B7L/6J mice were assigned to the normal control group.Huperzine A group,low-,mid-and high-dose TSG groups,model group and normal control group were respectively given by gavage with huperzine A(0.020 mg/kg),TSG(0.033,0.100,0.300 g/kg),0.9% sodium chloride solution(10.000 ml/kg),0.9% sodium chloride solution(10.000 ml/kg),once a day,for 60 days.At the end of intervention,all the mice were sacrificed and the brain tissues were taken out for experiments.Immunohistochemistry was used to determine the number of caspase-3 positive cells in each group mice′s cerebral cortex and hippocampus,and Western blotting was adopted to detect the expression level of APP in each group mice′s brain tissues.Results The number of caspase-3 positive cells in the cerebral cortex and hippocampus of the mice in the normal control group,huperzine A group and low-,mid-and high-dose TSG groups were less than those in the model group(P<0.05).The number of caspase-3 positive cells in the cerebral cortex and hippocampus of mice in huperzine A group was not significantly different from that of the mice in low-,mid-and high-dose TSG groups(P>0.05).The mice in the model group had higher expression level of APP in brain tissues than those in the normal control group,huperzine A group and low-,mid-and high-dose TSG groups(P<0.05).The expression level of APP in brain tissues of mice in huperzine A group did not differ substantially from that of the mice in low-,mid-and high-dose TSG groups(P>0.05).Conclusion TSG has obvious therapeutic effect on APP/PS1 double transgenic mice,the mechanism might be related to the inhibition of the expression levels of caspase-3 and APP so as to reduce the production of amyloid-β protein,and delay the apoptosis of nerve cells.%目的 观察二苯乙烯苷(TSG)对淀粉样前体蛋白(APP)/早老蛋白-1(PS1)双转基因小鼠脑组织半胱氨酸天冬氨酸蛋白酶3(caspase-3)、APP表达水平的影响,探讨其防治AD的可能机制.方法 2014年10月,将50只SPF级、雄性、APP/PS1双转基因小鼠按照随机数字表法分为模型组、石杉碱甲组、TSG低剂量组、TSG中剂量组、TSG高剂量组,每组10只.并选取10只SPF级、雄性、C5B7L/6J小鼠为正常对照组.石杉碱甲组小鼠灌胃给予石杉碱甲0.020 mg/kg,TSG低剂量组、TSG中剂量组、TSG高剂量组小鼠分别灌胃给予TSG 0.033、0.100、0.300 g/kg,模型组、正常对照组小鼠灌胃给予0.9%氯化钠溶液10.000 ml/kg;1次/d,连续给药60 d.采用免疫组化法检测各组小鼠脑皮质和海马区caspase-3阳性细胞数,Western blotting法检测各组小鼠脑组织APP表达水平.结果 正常对照组、石杉碱甲组、TSG低剂量组、TSG中剂量组、TSG高剂量组小鼠脑皮质、海马区caspase-3阳性细胞数少于模型组(P<0.05);TSG低剂量组、TSG中剂量组、TSG高剂量组小鼠脑皮质、海马区caspase-3阳性细胞数与石杉碱甲组比较,差异无统计学意义(P>0.05).正常对照组、石杉碱甲组、TSG低剂量组、TSG中剂量组、TSG高剂量组小鼠脑组织APP表达水平均低于模型组(P<0.05);TSG低剂量组、TSG中剂量组、TSG高剂量组小鼠脑组织APP表达水平与石杉碱甲组比较,差异无统计学意义(P>0.05).结论 TSG对APP/PS1双转基因小鼠有明显的治疗作用,其防治AD的机制可能与抑制caspase-3和APP表达、减少β淀粉样蛋白产生、减缓神经元凋亡等机制有关.
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