基于磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物西罗莫司靶蛋白通路途径髓样细胞触发受体2对胶质细胞炎症的影响

Effect of type 2 myeloid cell trigger receptor on glial cell inflammation based on the phosphoinositide-3-kinase/protein kinase B/mammalian target of sirolimus pathway

目的探究基于磷脂酰肌醇-3-激酶(phosphoinositide-3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)/哺乳动物西罗莫司靶蛋白(mammalian target of sirolimus,mTOR)通路途径髓样细胞触发受体2(triggering receptors expressed on myeloid cells-2,TREM2)对胶质细胞炎症的影响。方法对胶质细胞采用脂多糖(lipopolysaccharide,LPS)进行诱导造模后完成分组检测,分组如下:对照组、LPS处理组和TREM2组,通过RT-PCR方法检测白细胞介素(interleukin)-6、IL-1β和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)中mRNA表达水平,采用免疫印迹法检测各组细胞PI3K、AKT、mTOR蛋白表达水平。结果与对照组比较,LPS处理组、TREM2组IL-6、IL-1β和TNF-α中mRNA表达水平均升高,TREM2组IL-6、IL-1β、TNF-α中mRNA表达水平高于LPS处理组,差异有统计学意义(P<0.05)。LPS处理组和TREM2组细胞PI3K、AKT和mTOR蛋白表达水平均高于对照组,TREM2组细胞PI3K、AKT和mTOR蛋白表达水平高于LPS处理组,差异有统计学意义(P<0.05)。结论小胶质细胞过度活化后诱导神经炎症,P13K/AKT/mTOR信号通路参与多种神经退行性疾病的发生发展过程,其在细胞炎症反应中都发挥着重要作用。

Objective To explore the effect of triggering receptors expressed on myeloid cells-2(TREM2)on inflammatory cells based on the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway.Methods Glial cell cultures were induced with lipopolysaccharide(LPS),then divided into the following groups:control group;LPS-treated group;and TREM2group.The mRNA expression levels of interleukin-6(IL-6),IL-1β,and tumor necrosis factor-alpha(TNF-α)were detected by reverse transcription-polymerase chain reaction(RT-PCR).Western blot analysis was used to detect the protein expression levels of PI3K,AKT,mTOR in each group.Results The mRNA expression levels of IL-6,IL-1βand TNF-αwere increased in the LPS-treated group and the TREM2 group compared to the control group,the mRNA expression levels of IL-6,IL-1βand TNF-αin the TREM2 group were higher than those in the LPS-treated group(all P<0.05).Western blot analysis showed that the protein expression levels of PI3K,AKT and mTOR in the LPS-treated group and the TREM2 group were higher than those in the control group,the protein expression levels of PI3K,AKT and m TOR in the TREM2 group were significantly increased compared to the LPS-treated group(all P<0.05).Conclusions Neuroinflammation induced by excessive activation of microglia,the P13K/AKT/mTOR signaling pathway is involved in the occurrence and development of several neurodegenerative diseases,which plays an important role in the cellular inflammatory response.