Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice
Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice
复制标题
肠道菌群失调介导老年小鼠麻醉/手术引起的参考记忆缺陷
DOI：
10.1016/j.bbi.2019.05.006
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发表时间：
2019-08-01
影响因子：
15.1
通讯作者：
Su, D. S.
中科院分区：
文献类型：
--
作者：
Jiang, X. L.;Gu, X. Y.;Su, D. S.
背景术后认知功能障碍（POCD）与发病率和死亡率的增加有关，已成为患者和护理人员的主要关注点。POCD在老年患者中最常见。以前的研究表明，肠道微生物组影响认知功能和行为，围手术期因素，包括手术本身，抗生素，阿片类药物或酸诱导药物，影响肠道微生物组。因此，我们假设由麻醉/手术引起的肠道菌群失调诱导POCD。方法：18月龄C57 BL/6小鼠在异氟醚麻醉下行胫骨骨折内固定术，建立POCD模型。Morris水迷宫用于测量麻醉/手术后的参考记忆。来自粪便样品的16 S rRNA的高通量测序被用于研究麻醉/手术后肠道细菌丰度的变化。为了证实肠道微生物组在POCD中的作用，我们用复合抗生素或混合益生菌（VSL#3）预处理小鼠。麻醉/手术损害老年小鼠的参考记忆和诱导肠道菌群失调。结果：16 S rRNA测序数据显示，麻醉/手术后大量变化的细菌有37个属（18个科）。用复合抗生素或混合益生菌（VSL#3）预处理小鼠可预防麻醉/手术诱导的学习和记忆缺陷。我们进一步对37种细菌中的22种常见细菌进行了定量实时聚合酶链反应（qRT-PCR），以验证麻醉/手术后细菌植物群变化的结果。8种细菌的数量在麻醉/手术后发生变化，但在用益生菌混合物治疗后恢复正常。结论：我们的数据表明，在参考记忆缺陷诱导麻醉/手术是由肠道菌群失调介导的。
Background Postoperative cognitive dysfunction (POCD) is associated with increased morbidity and mortality and has become a major concern for patients and caregivers. POCD is most common in older patients. Previous studies demonstrated that the gut microbiome affects cognitive function and behaviour, and perioperative factors, including the operation itself, antibiotics, opioids or acid-inducing drugs, affect the gut microbiome. Thus, we hypothesised that intestinal dysbacteriosis caused by anaesthesia/surgery induces POCD. Methods: Tibial fracture internal fixation was performed in 18-month-old C57BL/6 mice under isoflurane anaesthesia to establish the POCD model. The Morris water maze was used to measure reference memory after anaesthesia/surgery. High-throughput sequencing of 16S rRNA from faecal samples was used to investigate changes in the abundance of intestinal bacteria after anaesthesia/surgery. To confirm the role of the gut microbiome in POCD, we pretreated mice with compound antibiotics or mixed probiotics (VSL#3). Anaesthesia/ surgery impaired reference memory and induced intestinal dysbacteriosis in aged mice. Results: The 16S rRNA sequencing data revealed 37 genera (18 families) of bacteria that changed in abundance after anaesthesia/surgery. Pretreating mice with compound antibiotics or mixed probiotics (VSL#3) prevented the learning and memory deficits induced by anaesthesia/surgery. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) of 22 common types of bacteria among the 37 total types to verify the results of bacterial flora changes after anaesthesia/surgery. Numbers of 8 types of bacteria changed after anaesthesia/surgery but returned to normal after treatment with a mix of probiotics. Conclusions: Our data suggest that deficits in reference memory induced by anaesthesia/surgery are mediated by intestinal dysbacteriosis.