上调Prdx6表达减轻七氟醚诱导的HT22海马神经元铁死亡研究  

Upregulation of Prdx6 mitigates sevoflurane-induced HT22 hippocampal neuronal ferroptosis

作　　者：李福军 郭力甲[2] 王顺[1] LI Fu-jun;GUO Li-jia;WANG Shun(Department of Acupuncture and Moxibustion,Heilongjiang College of Traditional Chinese Medicine,Harbin 150036,China;Department of Anesthesiology,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]黑龙江省中医药科学院针灸科,黑龙江哈尔滨150036 [2]哈尔滨医科大学附属第一医院麻醉科,黑龙江哈尔滨150001

出　　处：《哈尔滨医科大学学报》2021年第2期114-119,共6页Journal of Harbin Medical University

摘　　要：目的探讨过氧化物酶6(peroxiredoxin 6,Prdx6)在七氟醚(sevoflurane, Sev)引起的神经元损伤中的作用及机制。方法 HT22细胞予以不同浓度(0%、0.5%、1%、2%、3%、4%)的Sev处理6 h或暴露于3%的Sev中处理0、6、12、24 h。qRT-PCR和Western blot检测各组HT22细胞中Prdx6、p38和p-p38的mRNA和蛋白表达水平。CCK-8试剂盒检测HT22细胞的活性。采用相应的商业试剂盒检测细胞内铁离子、ROS和GSH的水平。结果随着Sev处理浓度的增加和时间延长,HT22细胞的活性随之降低(P<0.05)。铁死亡抑制剂Ferrostatin-1处理减轻了Sev对HT22细胞活性的抑制作用(P<0.05)。Sev处理的H22细胞中Prdx6的表达水平降低(P<0.05)。过表达Prdx6逆转了Sev对铁离子累积和ROS生成的促进作用,并消除了Sev对GSH的抑制作用(P<0.05)。过表达Prdx6抑制了Sev诱导的P38-MAPK信号通路的激活(P<0.05)。结论 Prdx6可能通过抑制P38-MAPK信号的激活来抑制Sev诱导的神经元铁死亡。Objective To explore the role of peroxiredoxin 6(Prdx6) in sevoflurane(Sev)-induced neuronal ferroptosis and its mechanism. Methods HT22 cells were treated with different concentrations(0%, 0.5%, 1%, 2%, 3%, 4%) of Sev at indicated times(0, 6, 12, 24 h). qRT-PCR and Western blot assay were used to detect the expression of Prdx6, p38 and p-p38, and cell viability was detected using CCK-8 kit. Corresponding commercial kits were applied to evaluate the levels of ROS, glutathione(GSH) and iron in HT22 cells. Results Sev administration reduced the viability of HT22 cells, in a dose-and time-dependent manner(P<0.05). Ferroptosis inhibitor Ferrostatin-1 treatment attenuated the inhibitory effect of Sev on the viability of HT22 cells(P<0.05). Sev administration decreased the expression of Prdx6 in HT22 cells(P<0.05). Prdx6 overexpression reversed Sev-induced iron accumulation and ROS production, as well as eliminated Sev-induced decrease in GSH levels(P<0.05). In addition, Prdx6 overexpression inhibited Sev-induced activation of the P38-MAPK signaling pathway(P<0.05). Conclusion Prdx6 mitigates Sev-induced neuronal ferroptosis by inhibiting the activation of the P38-MAPK signaling pathway.

关 键 词：七氟醚 铁死亡 神经元损伤 Prdx6 P38-MAPK信号通路 

分 类 号：R338.1[医药卫生—人体生理学]