咪达唑仑调控CX3CL1/CX3CR1通路对无镁诱导的神经元炎性损伤的影响OA
Effects of Midazolam Regulating the CX3CL1/CX3CR1 Pathway on Magnesium-free Induced Neuronal Inflammatory Injury
目的:探讨咪达唑仑(MDZ)调控 CX3C 趋化因子配体 1(CX3CL1)/CX3C 趋化因子受体1(CX3CR1)通路对无镁诱导的神经元炎性损伤的影响.方法:将原代海马神经元分为 Ctrl 组(正常培养)、无镁诱导组(用无镁外液处理神经元3h)、L-MDZ 组(0.1μmoL/L 的 MDZ 处理 2h+无镁外液处理3h)、M-MDZ 组(1.0μmoL/L 的 MDZ 处理 2h+无镁外液处理 3h)、H-MDZ 组(10μmoL/L 的 MDZ 处理2h+无镁外液处理3h)、AZD8797 组(10μmoL/L 的 MDZ+50nmoL/L 的 AZD8797 处理 2h+无镁外液处理神经元3h).测定各组 LDH 浓度;CCK-8 检测神经元增殖;流式细胞仪检测神经元凋亡;ELISA 法检测神经元中 IL-6、IL-1β、TNF-α 表达;WB 检测神经元中 PCNA、FOXM1、PLK1、CX3CL1、CX3CR1、Bim、Cleaved Caspase-3、MCL-1 蛋白表达.结果:无镁诱导组凋亡率、Bim、Cleaved Caspase-3、LDH、IL-6、IL-1β、TNF-α 高于 Ctrl 组,A450 值、PCNA、FOXM1、PLK1、MCL-1、CX3CL1、CX3CR1 低于 Ctrl 组(P<0.05);L-MDZ 组、M-MDZ 组、H-MDZ 组凋亡率、Bim、Cleaved Caspase-3、LDH、IL-6、IL-1β、TNF-α 低于无镁诱导组,A450 值、PCNA、FOXM1、PLK1、MCL-1、CX3CL1、CX3CR1 高于无镁诱导组(P<0.05);AZD8797 组凋亡率、Bim、Cleaved Caspase-3、LDH、IL-6、IL-1β、TNF-α 高于 H-MDZ 组,A450 值、PCNA、FOXM1、PLK1、MCL-1、CX3CL1、CX3CR1 低于 H-MDZ 组(P<0.05).结论:MDZ 通过激活 CX3CL1/CX3CR1 通路抑制无镁诱导的神经元炎性损伤.
Objective:To explore the effects of midazolam(MDZ)regulating the CX3C chemokine lig-and 1(CX3CL1)/CX3C chemokine receptor 1(CX3CR1)pathway on magnesium-free induced neuronal in-flammatory injury.Methods:Primary hippocampal neurons were assigned into the Ctrl group(normal cul-ture),the magnesium-free induction group(neurons were treated with magnesium-free extracellular fluid for 3 h),the L-MDZ group(treated with 0.1μmol/L MDZ for 2h followed by magnesium-free external solution for 3h),the M-MDZ group(treated with 1.0μmol/L MDZ for 2h followed by magnesium-free external solu-tion for 3h),the H-MDZ group(treated with 10μmol/L MDZ for 2 h followed by magnesium-free external solution for 3h),and the AZD8797 group(treated with 10μmol/L MDZ+50nmol/L AZD8797 for 2h followed by magnesium-free external solution for 3h).The LDH concentrations of each group were determined.CCK-8 was used to detect neuronal proliferation.Neuronal apoptosis was detected by flow cytometry.The expres-sions of IL-6,IL-1β and TNF-α in neurons were detected by ELISA.WB was conducted to measure the protein expressions of PCNA,FOXM1,PLK1,CX3CL1,CX3CR1,Bim,Cleaved Caspase-3 and MCL-1 in neurons.Results:The apoptosis rate,Bim,Cleaved Caspase-3,LDH,IL-6,IL-1β,and TNF-α in the magnesium-free induction group were higher than those in the Ctrl group,while the A450 value,PCNA,FOXM1,PLK1,MCL-1,CX3CL1,and CX3CR1 were lower than those in the Ctrl group(P<0.05).The apoptosis rate,Bim,Cleaved Caspase-3,LDH,IL-6,IL-1β and TNF-α in the L-MDZ group,M-MDZ group and H-MDZ group were lower than those in the magnesium-free induction group,while the A450 val-ue,PCNA,FOXM1,PLK1,MCL-1,CX3CL1 and CX3CR1 were higher than those in the magnesium-free induction group(P<0.05).The apoptosis rate,Bim,Cleaved Caspase-3,LDH,IL-6,IL-1β and TNF-α in the AZD8797 group were higher than those in the H-MDZ group,while the A450 value,PCNA,FOXM1,PLK1,MCL-1,CX3CL1 and CX3CR1 were lower than those in the H-MDZ group(P<0.05).Conclusion:MDZ inhibits magnesium-free induced neuronal inflammatory injury by activating the CX3CL1/CX3CR1 path-way.
武倩;许海峰;周瑞欣;王振云;刘亚妹
河北省沧州中西医结合医院麻醉一科,河北 沧州 061000河北省沧州中西医结合医院麻醉一科,河北 沧州 061000河北省沧州中西医结合医院麻醉一科,河北 沧州 061000河北省沧州中西医结合医院麻醉一科,河北 沧州 061000河北省沧州中西医结合医院麻醉一科,河北 沧州 061000
炎性损伤咪达唑仑CX3C趋化因子配体1CX3C趋化因子受体1无镁
Inflammatory injuryMidazolamCX3C chemokine ligand 1CX3C chemokine re-ceptor 1Magnesium-free
《河北医学》 2026 (6)
943-948,6
河北省卫生健康委医学科学研究课题计划项目(20241255)
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