Intestinal dysbacteriosis-propelled T helper 17 cells activation mediate the perioperative neurocognitive disorder induced by anesthesia/surgery in aged rats

肠道菌群失调促使辅助性T细胞17活化介导老年大鼠麻醉/手术诱发的围手术期神经认知障碍

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作者:Yazhou Wen, Shanwu Feng, Hongyu Dai, Meng Mao, Zhenhui Zhou, Bin Li, Chaoran Wang, Xuechun Cai, Shuming Li, Jiaojiao Yang, Quan Ren, Jie Sun

Background

Perioperative neurocognitive disorders (PND) is a common postoperative disease in elderly patients, but its pathogenesis remains unclear.

Conclusion

Our study suggested that intestinal dysbacteriosis-propelled T helper 17 cells activation and IL17 secretion might play an important role in the pathogenesis of PND induced by anesthesia/surgery in aged rats.

Methods

Exploratory laparotomy was performed to establish PND model under sevoflurane anesthesia. 16S rRNA high-throughput sequencing was used to detect the changes of intestinal flora. Antibiotics were used to relatively eliminate intestinal flora before anesthesia/surgery, and behavior tests, such as open field, Y maze, and fear conditioning tests were applied to detect the changes of memory ability. The number of Th17 cells and Foxp3 cells was detected by flow cytometry in the Peyer's patches (PP), mesenteric lymph nodes (MLN), blood and brain. Western blot was used to detect the expression of IL17, IL17RA, IL6 and IL10 in the hippocampus. Immunofluorescence was used to detect the expression of IL17, IL17R and IBA1 (ionized calcium binding adaptor molecule1) in the hippocampus.

Results

Anesthesia/surgery caused intestinal flora imbalance and induced neurocognitive impairment, increased the number of Th17 cells in the PP, MLN, blood and brain, increased the level of IL17, IL17R and inflammatory factors production in the hippocampus. Antibiotics administration before anesthesia/surgery significantly decreased the number of Th17 cells and the level of IL17, IL17R and inflammatory factors production, and improved the memory function. In addition, we found that IL17R was co-labeled with IBA1 in a large amount in the hippocampus through immunofluorescence double-staining.

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