| 薛 芬,薛姗姗,周翠红,王化宁,彭正午,吴 迪.海马Sirt1在高压氧预处理改善异氟醚诱导老龄小鼠认知功能障碍中的作用[J].现代生物医学进展英文版,2020,(22):4213-4217. |
| 海马Sirt1在高压氧预处理改善异氟醚诱导老龄小鼠认知功能障碍中的作用 |
| Sirt1 Mediates Improvement of Isoflurane-induced Memory Impairment Following Hyperbaric Oxygen Preconditioning |
| Received:April 26, 2020 Revised:May 21, 2020 |
| DOI：10.13241/j.cnki.pmb.2020.22.003 |
| 中文关键词: 术后认知功能障碍 高压氧预处理 沉默信息调节因子1 |
| 英文关键词: POCD HBO - PC Sirt1 |
| 基金项目:国家自然科学基金项目(81571309；81904280) |
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| 中文摘要: |
| 摘要 目的：通过shRNA抑制沉默信息调节因子1（sirtuin 1，Sirt1）基因表达，研究Sirt1在高压氧预处理改善异氟醚（isoflurane，ISO）诱导小鼠认知功能障碍中的作用及其对小鼠海马BDNF、GDNF基因表达的影响。方法： 将64只C57雄性小鼠随机分为假手术组（Sham组）、高压氧组（HBO组）、异氟醚组（ISO组）、高压氧预处理+异氟醚组（HBO + ISO组）；以及对照组（NS组）、Sirt1抑制组（sh-Sirt1组）、对照+高压氧预处理组（NS + HBO组）和Sirt1抑制+高压氧预处理组（sh-Sirt1 + HBO组），每组8只。经慢病毒转染以及ISO末次暴露24小时后进行认知功能测试（Morris水迷宫测试），随后处死小鼠，利用实时荧光定量聚合酶链反应（RT-qPCR）检测海马BDNF和GDNF的mRNA表达情况。结果：（1）异氟醚可以导致明显的认知功能障碍，与Sham组相比，ISO组靶象限探索时间百分比显著减低（P<0.01），ISO组小鼠海马BDNF和GDNF mRNA表达水平显著下降（P<0.01）。（2）高压氧预处理可以改善POCD小鼠的认知功能障碍，ISO + HBO组靶象限探索时间百分比显著高于ISO组（P<0.05），ISO + HBO组小鼠海马BDNF（P<0.05）和GDNF（P<0.01）mRNA表达水平显著升高。（3）高压氧预处理可以显著增加POCD小鼠海马BDNF（P<0.01）和GDNF（P<0.05）mRNA表达水平，慢病毒介导shRNA靶向下调Sirt1可以逆转高压氧预处理对POCD小鼠海马BDNF（P<0.05）和GDNF（P<0.01）mRNA表达水平的改变。结论：高压氧预处理是治疗POCD的有效方法，Sirt1可能是POCD治疗的潜在分子靶点。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the role of Sirt1 in hyperbaric oxygen preconditioning to isoflurane induced cognitive dysfunction in mice and the effect of BDNF and GDNF expression in mice. Methods: 64 C57 male mice were randomly divided into sham group,HBO group, ISO group, HBO+ISO group; and NS group, sh-Sirt1 group, sh-Sirt1+HBO group, NS+HBO group (8 in each group). After the last exposure for 24 hours or lentivirus transfection, the cognitive function test (Morris water maze test) was carried out, and then the mice were killed. The mRNA levels of BDNF and GDNF in hippocampus was measured by Real-time PCR. Results: (1) Isoflurane could cause significant cognitive impairment. Compared with sham group, the percentage of target quadrant exploration time in ISO group was significantly reduced (P<0.01), and the expression level of BDNF and GDNF mRNA in hippocampus of ISO group was significantly decreased (P<0.01). (2) Hyperbaric oxygen pretreatment can improve the cognitive dysfunction of POCD mice. The percentage of target quadrant exploration time in ISO+HBO group was significantly higher than that in ISO group (P<0.05). The mRNA expression levels of BDNF(P<0.05) and GDNF(P<0.01) in hippocampus of ISO+HBO group were significantly increased. (3) HBO pretreatment could significantly increase the expression of BDNF(P<0.01) and GDNF(P<0.05) mRNA in the hippocampus of POCD mice. SIRT1 down-regulated by shRNA mediated by lentivirus could reverse the changes of BDNF (P<0.05) and GDNF (P<0.01) mRNA expression in the hippocampus of POCD mice. Conclusion: HBO preconditioning is a useful treatment for POCD and that Sirt1 may be a potential molecular target for POCD therapy. |
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