高压氧调控TLR4/NF-κB通路对脓毒症大鼠海马区细胞凋亡的影响

Effects of Hyperbaric Oxygen Regulation of TLR4/NF-κB Pathway on Apoptosis in Hippocampus of Septic Rats

目的:探究高压氧(hyperbaric oxygenation,HBO)调控Toll样受体4(Toll-like receptor 4,TLR4)/核因子(nuclear factor,NF)-κB通路对脓毒症相关性脑病(sepsis-associated encephalopathy,SAE)大鼠海马区细胞凋亡的影响。方法:将45只大鼠随机分为对照组、SAE组和SAE+HBO组(n=15),腹腔注射LPS构建SAE模型(15mg/kg,3d),SAE+HBO组大鼠每日接受HBO干预。检测和比较各组脑神经功能、海马体神经元损伤、凋亡、炎性反应水平,评估海马体中TLR4和NF-κB转录和翻译水平。结果:三组大鼠上述各指标比较差异显著(P<0.05)。SAE组的逃避潜伏期(44.06±5.12s)、IL-1β(76.25±8.06pg/mL)、IL-6(91.37±10.74pg/mL)、海马神经元损伤和凋亡(6.17±0.78个/视野)、TLR4和NF-κB mRNA和蛋白水平显著高于对照组,穿越平台次数(2.94±0.35次)显著低于对照组(P<0.05)。SAE+HBO组的逃避潜伏期(35.86±3.06s)、IL-1β(48.68±5.21pg/mL)、IL-6(64.47±7.06pg/mL)、海马神经元损伤和凋亡(3.42±0.52个/视野)、TLR4和NF-κB mRNA和蛋白水平显著低于SAE组,穿越平台次数(4.98±0.66次)显著高于SAE组(P<0.05)。结论:HBO可能通过抑制TLR4/NF-κB通路缓解SAE引起的海马神经元损伤和凋亡,进而保护神经功能。

Objective:To explore the effect of hyperbaric oxygen(HBO)on apoptosis in hippocampus of rats with sepsis-related encephalopathy(SAE)by regulating the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB pathway.Methods:45 rats were randomly divided into control group,SAE group and SAE+HBO group(n=15).The SAE model was constructed by intraperitoneal injection of LPS(15 mg/kg,3 days).Rats in SAE+HBO group received HBO intervention daily.The cranial nerve function,hippocampal neuron damage,apoptosis,and inflammatory response levels in each group were tested and compared.TLR4 and NF-κB transcription and translation levels in the hippocampus were detected.Results:The above indicators of the three groups of rats were significantly different(P<0.05).The escape latency(44.06±5.12 s),IL-1β(76.25±8.06 pg/mL),IL-6(91.37±10.74 pg/mL),hippocampal neuron damage and apoptosis(6.17±0.78 cells/field of view),TLR4 and NF-κB mRNA and protein levels in SAE group were significantly higher than those of the control group,and the number of crossing platforms(2.94±0.35 times)was significantly lower than that of the control group(P<0.05).The escape latency(35.86±3.06 s),IL-1β(48.68±5.21 pg/mL),IL-6(64.47±7.06 pg/mL),hippocampal neuron damage and apoptosis(3.42±0.52 cells/field of view),TLR4 and NF-κB mRNA and protein levels in the SAE+HBO group were significantly lower than those in the SAE group,and the number of crossing platforms(4.98±0.66 times)was significantly higher than in the SAE group(P<0.05).Conclusion:HBO may alleviate the damage and apoptosis of hippocampal neurons caused by SAE by inhibiting the TLR4/NF-κB pathway,thereby protecting nerve function.