黄芪甲苷基于MEK5/ERK5信号通路对阿尔茨海默病大鼠小胶质细胞活性的影响

Effect of astragalosideⅣon microglia activity in Alzheimer’s disease rats based on MEK5/ERK5 signaling pathway

目的研究黄芪甲苷基于丝裂原激活蛋白激酶5(MEK5)/细胞外信号调节激酶5(ERK5)信号通路对阿尔茨海默病(AD)大鼠小胶质细胞活性的影响。方法清洁级健康SD雄性大鼠60只,随机选取10只为正常组,其余50只建立AD模型,然后随机分为模型组、阳性对照组、黄芪甲苷低剂量组、黄芪甲苷中剂量组、黄芪甲苷高剂量组,每组10只。阳性对照组给予石杉碱甲(0.02 mg/kg)干预,正常组和模型组分别给予等体积的0.9%NaCl溶液,黄芪甲苷低剂量组、黄芪甲苷中剂量组、黄芪甲苷高剂量组分别给予15 mg/kg、30 mg/kg、60 mg/kg的黄芪甲苷。各组均干预21 d,检测白介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)水平,以及葡萄糖调节蛋白78(GRP78)、C/EBP同源蛋白(CHOP)、MEK5、ERK5表达。结果与正常组相比,模型组、阳性对照组、黄芪甲苷低剂量组、黄芪甲苷中剂量组、黄芪甲苷高剂量组IL-1、TNF-α水平及GRP78、CHOP、MEK5、ERK5表达升高(P<0.05);与模型组相比,阳性对照组、黄芪甲苷低剂量组、黄芪甲苷中剂量组、黄芪甲苷高剂量组IL-1、TNF-α水平及GRP78、CHOP、MEK5、ERK5表达降低,且随剂量增加而降低(P<0.05)。结论黄芪甲苷基于MEK5/ERK5信号通路对AD大鼠小胶质细胞的活性具有抑制作用,可减少AD大鼠神经细胞的凋亡。

Objective To investigate the effect of AstragalosideⅣon microglia activity in Alzheimer’s disease(AD)rats based on mitogen activated protein kinase 5(MEK5)/extracellular signal regulated kinase 5(ERK5)signaling pathway.Methods Sixty clean grade healthy SD male rats were selected,and 10 were randomly selected as a normal group.The remaining 50 were randomly divided into the model group,the positive control group,the astragalosideⅣlow dose group,the AstragalosideⅣmedium dose group and the AstragalosideⅣhigh dose group after the establishment of the AD model,with 10 rats in each group.The positive control group was intervened with huperzine A(0.02 mg/kg),the normal group and model group were administered with the equal volume of 0.9%NaCl solution,and the astragalosideⅣlow dose group,the AstragalosideⅣmedium dose group and the astragalosideⅣhigh dose group were administered with 15 mg/kg,30 mg/kg and 60 mg/kg of AstragalosideⅣ,respectively.All groups were intervened for 21 days.Interleukin-1(IL-1)and tumor necrosis factor-α(TNF-α)levels as well as the expressions of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP),MEK5 and ERK5 were tested.Results Compared with normal group,the levels of IL-1,TNF-αand the expressions of GRP78,CHOP,MEK5 and ERK5 in model group,positive control group,low dose astragalosideⅣgroup,medium dose astragalosideⅣgroup and high dose astragalosideⅣgroup were increased(P<0.05).Compared with model group,the levels of IL-1,TNF-αlevels and the expressions of GRP78,CHOP,MEK5 and ERK5 in positive control group,low dose astragalosideⅣgroup,medium dose astragalosideⅣgroup and high dose astragalosideⅣgroup were decreased in a dose-dependent manner,and also decreased with dose increase(P<0.05).Conclusion AstragalosideⅣcan inhibit the activity of microglia and reduce the apoptosis of neurons in AD rats based on MEK5/ERK5 signaling pathway.