桑辛素对D-半乳糖致小鼠老年性痴呆模型的保护作用及机制研究

Protective effect and mechanism of morusin on D-galactose induced alzheimer disease in mice

[目的]研究桑辛素对D-半乳糖致小鼠老年性痴呆的保护作用,并初步探讨其作用机制。[方法]采用皮下注射D-半乳糖100 mg/(kg·d),连续8周,建立小鼠痴呆模型。桑辛低中高剂量组分别灌胃给药10、20、40 mg/(kg·d),吡拉西坦组灌胃给药0.75 g/(kg·d),空白对照组灌胃给予等量蒸馏水。给药8周后,利用Morris水迷宫检测各组小鼠学习记忆能力,苏木精-伊红(HE)染色观察脑组织海马齿状回结构的病理变化。检测血清肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)的含量;检测脑组织乙酰胆碱转移酶(ChAT)活性、乙酰胆碱(ACH)含量以及p53蛋白的表达。[结果]与空白对照组比较,模型组小鼠的逃避潜伏期明显延长,站台穿越次数明显减少(P<0.01),脑海马齿状回神经元损伤严重,血清TNF-α和IL-1β的含量升高(P<0.01),脑组织ChAT活性和ACH含量明显降低(P<0.01),p53蛋白的表达量明显升高(P<0.01)。与模型组比较,桑辛素给药组的逃避潜伏期明显缩短(P<0.05或P<0.01),站台穿越次数明显增加(P<0.05或P<0.01),脑海马神经元损伤明显改善,血清TNF-α和IL-1β的含量降低(P<0.05或P<0.01),脑组织ChAT活性和ACH含量明显升高(P<0.05或P<0.01),p53蛋白的表达量明显降低(P<0.05或P<0.01),呈剂量依赖性。吡拉西坦组上述指标也明显改善。[结论]桑辛素对D-半乳糖致小鼠老年性痴呆具有较好的保护作用,其作用机制可能与减轻炎症、抑制凋亡和增加神经突触间的ACH含量和ChAT活性有关。

[Objective] To explore the protective effect of morusin on D-galactose induced alzheimer disease in mice and its possible mechanisms. [Methods] AD model was established by subcutaneous injection of D-galactose 100 mg/(kg·d) for 8 weeks. The dose of lowdose morusin group,middle-dose morusin group,high-dose morusin group and piracetam group were 10,20,40 mg/(kg·d),and 0.75 g/(kg·d).After 8 weeks of administration,the learning and memory ability of mice were tested by Morris water maze. The pathological changes of hippocampal dentate gyrus were observed by HE staining. The content of TNF-α and IL-1β in serum was detected. The activity of ChAT,the content of ACH and the expression of p53 protein in brain tissue were detected. [Results] Compared with the control group,the escape latency in the model group were significantly increased. The numbers of passing through the platform were obviously reduced( P<0.01). Neurons in the brain’s dentate gyrus were severely damaged. The levels of TNF-α and IL-1β in serum were increased. The activity of ChAT and the content ACH in brain tissue were decreased(P<0.01). The expression of p53 protein was significantly increased(P<0.01).Compared with the model group,the escape latency in the morusin group were significantly decreased(P<0.05 or P<0.01). The numbers of passing through the platform were obviously increased(P <0.05 or P <0.01). Neurons in the brain’s dentate gyrus were obviously improved. The levels of TNF-α and IL-1β in serum were decreased(P<0.05 or P<0.01). The activity of ChAT and the content ACH in brain tissue were increased(P <0.05 or P <0.01). The expression of p53 protein was significantly decreased(P <0.05 or P <0.01) and appeared dose-dependent. The above index were improved in piracetam group. [Conclusions] Morusin has protecting effects on Dgalactose induced alzheimer disease in mice. The mechanism may be related to reducing inflammation,inhibiting apoptosis,increasing the content of ACH and the activity of ChAT in synapses.