法舒地尔对Aβ_(1-42)诱导的阿尔茨海默症PC12细胞的保护作用

Protective effects of fasudil′s against Alzheimer′s disease PC12 cells induced by Aβ_(1-42)

目的探究法舒地尔对阿尔茨海默症(AD)体外模型中的Aβ_(1-42)及p-Tau蛋白在氧化应激方面的影响。方法不同浓度Aβ_(1-42)作用于PC12细胞后,用CCK8法检测Aβ_(1-42)对PC12细胞活力的影响,从而建立AD的体外细胞模型。经法舒地尔治疗后,用免疫荧光法检测p-Tau蛋白和Aβ_(1-42)的表达水平,同时检测凋亡信号调节激酶1(ASK1)表达情况。结果1.0μmol/L Aβ_(1-42)对PC12细胞的增殖活性具有抑制作用,进一步验证Aβ_(1-42)在神经细胞中的毒害作用。同时,法舒地尔的加入能够降低p-Tau蛋白和Aβ_(1-42)的表达水平,表明法舒地尔能够减轻Aβ_(1-42)对细胞的毒性作用。此外,法舒地尔通过调节细胞内信号转导通路,减少细胞凋亡和炎症反应,下调p-ASK1的表达水平,保护PC12细胞免受Aβ_(1-42)的损害。结论法舒地尔对Aβ_(1-42)诱导的阿尔茨海默症PC12细胞具有保护作用,能够抑制疾病发展中的关键病理变化。

Objective To investigate the effects of fasudil on p-Tau protein and Aβ_(1-42)in oxidative stress in an in vitro model of Alzheimer′s disease(AD).Methods Following exposure to varying concentrations of Aβ_(1-42)(1μmol/L)on PC12 cells,the CCK8 assay was employed to investigate the impact of Aβ_(1-42)on PC12 cell viability,thereby creating a cellular model of AD.Immunofluorescence was used to measure the expression levels of the p-Tau and Aβ_(1-42)following fasudil treatment.The expression of apoptosis signal-regulated kinase 1(ASK1)was also detected.Simultaneously,fasudil treatment was able to lower the levels of Aβ_(1-42)and p-Tau expression,indicating that fasudil was able to lessen the harmful effects of Aβ_(1-42)on cells.Furthermore,fasudil inhibited p-ASK1 expression and shielded PC12 cells from Aβ_(1-42)damage by controlling intracellular signaling pathways,lowering inflammatory reactions,and apoptosis.Results The detrimental impact of Aβ_(1-42)on neural cells was further confirmed by its inhibitory effect on PC12 cells′proliferative activity at a concentration of 1μmol/L.Meanwhile,the addition of fasudil was able to reduce the expression levels of p-Tau protein and Aβ_(1-42),indicating that fasudil was able to mitigate the toxic effects of Aβ_(1-42)on cells.Additionally,fasudil reduced p-ASK1 expression levels and protected PC12 cells by regulating intracellular signaling pathways,reducing apoptosis and inflammation.Conclusion Fasudil has a protective effect on Aβ_(1-42)-induced Alzheimer′s disease PC12 cells,which can inhibit key pathological changes in disease development,reduce the expression of p-Tau and Aβ_(1-42),improve the damage caused by oxidative stress and downregulate p-ASK1 expression levels,which has promising applications in the treatment of Alzheimer′s disease.