基于ER-P38/MAPK信号通路探讨柚皮苷对Aβ_(25-35)致PC12细胞凋亡调控效应

Discussion on regulating effect of naringin on Aβ_(25-35)induced PC12 cell apoptosis based on ER-P38/MAPK signaling pathway

目的:研究柚皮苷(NG)对Aβ_(25-35)损伤PC12细胞中ER-P38/MAPK信号通路的调控效应。方法:以NG为受试药物,使用Aβ_(25-35)损伤PC12细胞建立阿尔茨海默症(AD)细胞模型,MTT法检测细胞增殖率,Western Blot法检测各组在阻断ER与P38-MAPK信号通路前后ERβ、p-P38/P38、Bcl-2、Caspase-3蛋白表达量的变化,探究NG对Aβ_(25-35)致PC12细胞损伤的保护作用。结果:与模型组比较,NG+Aβ_(25-35)组可引起受试PC12细胞中ERβ、Bcl-2蛋白表达显著升高以及p-P38/P38、Caspase-3表达显著降低(P<0.01);阻断ER后,与NG+Aβ_(25-35)组比较,NG+Aβ_(25-35)+ICI182780组ERβ和Bcl-2的表达显著降低(P<0.01),p-P38/P38和Caspase-3表达升高(P<0.01);阻断P38-MAPK通路后,与NG+Aβ_(25-35)组比较,NG+Aβ_(25-35)+SB203580组Bcl-2的表达降低(P<0.01),p-P38/P38和Caspase-3表达升高(P<0.01)。结论:NG可通过对ER-P38/MAPK途径的调控,减少受损PC12细胞的细胞凋亡,NG可作为神经保护剂进行深入开发。

Objective:To study the regulating effect of naringin(NG)on the ER-P38/MAPK signaling pathway in PC12 cells damaged by Aβ_(25-35).Methods:With NG as the test drug,Aβ_(25-35)was used to damage PC12 cells to establish an Alzheimer’s disease(AD)cell model.MTT method was used to detect cell proliferation rate,and Western Blot method was used to detect ERβand p-P38/P38,Bcl-2,Caspase-3 protein expression changes,to explore the protective effect of NG on Aβ_(25-35)induced PC12 cell injury.Results:Compared with the model group,the NG+Aβ_(25-35)group could significantly increase the protein expressions of ERβand Bcl-2 and significantly decrease the expressions of p-P38/P38 and Caspase-3 in the PC12 cells tested(P<0.01);blocking ER compared with the NG+Aβ_(25-35)group,the NG+Aβ_(25-35)+ICI182780 group could significantly reduce the expression of ERβand Bcl-2(P<0.01),and increase the expression of p-P38/P38 and Caspase-3(P<0.01);after blocking the P38-MAPK pathway,compared with the NG+Aβ_(25-35)group,the NG+Aβ_(25-35)+SB203580 group could reduce the expression of Bcl-2(P<0.01),and increase p-P38/P38 and Caspase-3 expression(P<0.01).Conclusion:NG can reduce the apoptosis of damaged PC12 cells by regulating the ER-P38/MAPK pathway.NG can be further developed as a neuroprotective agent.