Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids.

Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids.
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头孢唑林通过调节血脑屏障功能、肠道细菌和短链脂肪酸改善麻醉和手术引起的认知障碍。

DOI:
10.3389/fnagi.2021.748637
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发表时间:
2021
影响因子:
4.8
通讯作者:
Hua D
Hua D
中科院分区:
医学2区
文献类型:
--
作者:
Luo A;Li S;Wang X;Xie Z;Li S;Hua D

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新出现的证据表明,麻醉和手术可能会导致肠道生态失调。肠道生态失调导致微生物群衍生的代谢物的循环内容物的不平衡,并破坏血脑屏障(BBB)的完整性,从而导致术后认知功能障碍(POCD)。肠道微生物群的组成可能会受到各种抗生素的影响。然而,围手术期抗生素的使用如何影响POCD需要更多的探索。在本研究中,我们探讨了头孢唑林,围手术期常用的抗生素,对认知功能,血脑屏障的完整性,肠道细菌和短链脂肪酸(SCFAs),一组广泛研究的代谢产物在老年小鼠,使用18个月大的雄性小鼠的影响。POCD模型小鼠血脑屏障明显破坏,紧密连接蛋白ZO-1和OCLN水平降低。头孢唑林治疗减弱了麻醉和手术引起的这些变化。此外,头孢唑林逆转了几种粪便细菌(β-、γ/δ-、ε-变形菌门和拟杆菌门)的变化,如qPCR试验所示。血浆SCFAs的分析表明,几乎所有类型的SCFAs减少POCD和头孢唑林管理逆转表达的变化,两个最丰富的SCFAs(乙酸和丙酸)。总之,本研究表明,头孢唑林改善POCD。从机制上讲,头孢唑林抑制BBB、肠道微生物群或SCFA的破坏,从而改善POCD。
Emerging evidence suggests that anesthesia and surgery may induce gut dysbiosis. Gut dysbiosis leads to imbalance in circulating contents of microbiota-derived metabolites and disrupts the integrity of the blood-brain barrier (BBB), contributing to postoperative cognitive dysfunction (POCD). The composition of gut microbiota may be influenced by various antibiotics. However, how perioperative use of antibiotics affects POCD needs more explorations. In the present study, we explored the effect of cefazolin, a common antibiotic used in perioperative period, on cognitive function, BBB integrity, gut bacteria and short chain fatty acids (SCFAs), a group of widely studied metabolites in aged mice, using 18-month-old male mice. Significant BBB disruptions and decreased levels of tight junction proteins, zonula occludens-1 (ZO-1) and Occludin (OCLN) were seen in the mice of POCD model. Cefazolin treatment attenuated these changes induced by anesthesia and surgery. Furthermore, cefazolin reversed the changes in several fecal bacteria (β-, γ/δ-, ε-Proteobacteria, and Bacteroidetes) as determined by qPCR tests. Analysis of plasma SCFAs showed that almost all types of SCFAs were reduced in POCD and cefazolin administration reversed the changes in expression of the two most abundant SCFAs (acetic and propionic acids). In conclusion, this study demonstrated that cefazolin improved POCD. Mechanistically, cefazolin suppressed the disruption of BBB, gut microbiota or SCFAs, thereby ameliorating POCD.
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