摘要目的:基于沉默信息调节因子1/叉头转录因子O1(SIRT1/FoxO1)信号通路探讨高压氧(HBO)对脑缺血再灌注(CIR)大鼠血脑屏障(BBB)的保护作用。方法:选取雄性Wistar大鼠40只，按照随机数字表法将其分成假手术组(Sham组)、模型组(CIR组)、CIR+HBO组、CIR+HBO+ SIRT1抑制剂(EX527)组，每组10只。采用改良线栓法建立大鼠右侧大脑中动脉栓塞模型，Sham组大鼠不进行结扎和线栓导入，CIR+HBO组和CIR+HBO+EX527组予以HBO干预，CIR+HBO+EX527组在此基础上再予以EX527处理。CIR+HBO组和CIR+HBO+EX527组于再灌注1 h、9 h、21 h、45 h、69 h进入HBO舱，期间行HBO治疗5次。在处死动物前1 h，经尾静脉注射2%伊文思兰(EB)，采用比色法、逆转录-聚合酶链(RT-PCR)和Western blot法分别检测再灌注72 h大鼠海马区脑组织EB含量，SIRT1、FoxO1、ZO-1、Occludin、Claudin-5 mRNA及蛋白表达变化。结果:CIR 72 h，CIR组、CIR+HBO组和CIR+HBO+EX527组大鼠海马区脑组织EB含量均较Sham组明显增加( P<0.05)，CIR+HBO+XE527组大鼠海马区脑组织EB的含量较CIR+HBO组显著增加( P<0.05)。CIR 72 h，CIR组、CIR+HBO组和CIR+HBO+EX527组大鼠海马区脑组织SIRT1、FoxO1、ZO-1、Occludin、Claudin-5 mRNA表达及其相应蛋白表达较Sham组均显著降低( P<0.05)，CIR+HBO+EX527组大鼠海马区脑组织SIRT1、FoxO1、ZO-1、Occludin、Claudin-5 mRNA表达及其相应蛋白表达较CIR+HBO组显著降低( P<0.05)。 结论:HBO可以通过SIRT1/FoxO1通路增加紧密连接蛋白的表达，从而在CIR损伤中对BBB起到保护作用。

abstractsObjective:To explore the effect of hyperbaric oxygen (HBO) on the blood-brain barrier via the silent information regulator 1 (SIRT1)/Forkhead box O1(FoxO1) signaling pathway after cerebral ischemia and reperfusion using a rat model.Methods:Forty Wistar rats were randomly assigned into sham, cerebral ischemia-reperfusion (CIR), CIR+ HBO and CIR+ HBO+ EX527 groups, each of 10. The cerebral ischemia-reperfusion model was established in all groups except the sham group by right middle cerebral artery occlusion using the modified thread-occlusion method. The sham group was not ligated. Both the CIR+ HBO and CIR+ HBO+ EX527 groups were given HBO 1, 9, 21, 45 and 69 hours after the reperfusion. The CIR+ HBO+ EX527 group was additionally injected with 5mg/kg of EX527(a SIRT1inhibitor) peritoneally 4, 12, 24, 48 and 72 hours after the reperfusion. Then 2% Evens blue (EB) was injected into the tail vein an hour before the rats were sacrificed. The content of EB and the expression of SIRT1, FoxO1, ZO-1, Occludin, Claudin-5 mRNA and their proteins were determined using spectrophotometry, reverse transcription-polymerase chain reactions and Western blotting.Results:The average EB content of the hippocampal brain tissue from the CIR, CIR+ HBO and CIR+ HBO+ EX527 rats was significantly greater than the Sham group′s average 72h after reperfusion. The average expression of SIRT1, FoxO1, ZO-1, Occludin and Claudin-5 mRNA and their proteins was significantly lower, with the CIR + HBO + EX 527 group′s average significantly lower than that of the CIR+ HBO group.Conclusions:HBO can increase the expression of tight junction protein via the SIRT1/FoxO1 pathway. It helps to protect the blood-brain barrier in CIR injury situations.