佟雪,张倩茹,赵红,等.基于SIRT1/FoxO1信号通路探讨高压氧对脑缺血再灌注损伤大鼠血脑屏障的影响[J].中华物理医学与康复杂志,2022,44(1):13-17
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| 基于SIRT1/FoxO1信号通路探讨高压氧对脑缺血再灌注损伤大鼠血脑屏障的影响 |
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| DOI：10.3760/cma.j.issn.0254-1424.2022.01.002 |
| 中文关键词: 高压氧 血脑屏障 脑缺血再灌注 SIRT1 FoxO1 紧密连接蛋白 |
| 英文关键词: Hyperbaric oxygen Blood-brain barrier Cerebral ischemia and reperfusion Silent information regulator 1 Forkhead box O1 Tight junction protein |
| 基金项目:辽宁省科技厅博士启动基金资助项目（20101149） |
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| 摘要点击次数: 1998 |
| 全文下载次数: 15365 |
| 中文摘要: |
| 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。 |
| 英文摘要: |
| Objective 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. |
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