Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, PR China.
Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xianning West Road, Xi'an, Shaanxi, 710049, PR China.
Brain Res Bull. 2020 Nov;164:249-256. doi: 10.1016/j.brainresbull.2020.08.017. Epub 2020 Sep 5.
Increased permeability of blood-brain barrier (BBB) is a major pathophysiological mechanism of postoperative cognitive dysfunction (POCD) in the elderly. The reduced beneficial gut microbiome due to aging results in a decline in the production of sodium butyrate (NaB), which might enhance the BBB permeability. The present study investigated whether gut microbiome or NaB could improve the postoperative cognitive function in aged and gut dysbiosis mouse model.
A total of 210 male C57BL/6 J mice were randomly and equally divided into 7 groups (young control, young anesthesia/surgery, young anesthesia/surgery + antibiotic, aged control, aged anesthesia/surgery, aged anesthesia/surgery + Lactobacillus, aged anesthesia/surgery + NaB). Lactobacillus mix and antibiotic mix were administered by oral gavage to establish the gut dysbiosis and microbiome restoration model. Splenectomy was performed under sevoflurane anesthesia. Spatial memory learning ability was measured by Y maze. BBB permeability was detected by FITC-dextran imaging and brain tissue dextran spectrum. Tight junction (TJ) protein of hippocampus brain tissue was quantitated by Western blot.
Aging and antibiotic mix decreased the expression of the TJ, increased the BBB permeability and induced POCD, which could be reversed by the application of Lactobacillus and NaB.
Lactobacillus and NaB increased the expression of TJ protein between endothelial cells (ECs), reduced the BBB permeability, and consequently protected the postoperative cognitive functions of the aged and gut dysbiosis mice.
血脑屏障（BBB）通透性增加是老年人术后认知功能障碍（POCD）的主要病理生理机制。由于衰老导致有益的肠道微生物组减少，导致丁酸（NaB）的产生减少，这可能会增强 BBB 的通透性。本研究旨在探讨肠道微生物组或 NaB 是否可以改善老年和肠道失调小鼠模型的术后认知功能。
将 210 只雄性 C57BL/6J 小鼠随机平均分为 7 组（年轻对照组、年轻麻醉/手术组、年轻麻醉/手术+抗生素组、老年对照组、老年麻醉/手术组、老年麻醉/手术+乳酸杆菌组、老年麻醉/手术+NaB 组）。通过口服灌胃给予乳酸杆菌混合物和抗生素混合物建立肠道失调和微生物组恢复模型。在七氟醚麻醉下进行脾切除术。通过 Y 迷宫测量空间记忆学习能力。通过 FITC-葡聚糖成像和脑组织葡聚糖谱检测 BBB 通透性。通过 Western blot 定量海马脑组织紧密连接（TJ）蛋白。
衰老和抗生素混合物降低了 TJ 的表达，增加了 BBB 的通透性，并诱导了 POCD，而应用乳酸杆菌和 NaB 可以逆转这种情况。
乳酸杆菌和 NaB 增加了内皮细胞（ECs）之间 TJ 蛋白的表达，降低了 BBB 的通透性，从而保护了老年和肠道失调小鼠的术后认知功能。
