Mechanism of short-chain fatty acids reducing cognitive dysfunction in septic mice: transcriptomic analysis
10.3760/cma.j.cn131073.20240212.00616
- VernacularTitle:短链脂肪酸降低脓毒症小鼠认知功能障碍的机制：转录组学分析
- Author:
Meisha SUN
1
;
Yunfen TIAN
;
Lan LUO
;
Fangxiang ZHANG
;
Bin WANG
Author Information
1. 贵州省人民医院麻醉科，贵阳 550002
- Keywords:
Fatty acids;
Sepsis;
Cognitive dysfunction;
Transcriptome
- From:
Chinese Journal of Anesthesiology
2024;44(6):723-728
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the mechanism of short-chain fatty acids (SCFAs) reducing cognitive dysfunction in septic mice through transcriptomic analysis.Methods:Sixty SPF healthy adult male C57BL/6 mice, aged 8-12 weeks, weighing 20-25 g, were divided into 3 groups ( n=20 each) using a random number table method: sham operation group (Sham group), sepsis group (SEP group), and SCFAs+ sepsis group (SCFAs+ SEP group). Cecal ligation and puncture (CLP)was used to simulate a sepsis model in anesthetized animals. In SCFAs+ SEP group, 67.5 mmol/L acetate, 40 mmol/L butyrate, and 25.9 mmol/L propionate were added to drinking water starting from 14 days before CLP until 14 days after CLP. Y maze tests were conducted on days 4, 7 and 14 after surgery, with the number of mice in the Y maze test being the number of surviving mice on that day. On day 14 after surgery, 4 mice were selected in SEP group and SCFAs+ SEP group and sacrificed after anesthesia, and brain tissues were obtained to perform transcriptome sequencing, and enrichment analysis was performed using GO database and KEGG database. Finally, 5 mice were randomly sacrificed in each group, and brain tissues were collected and Western blot analysis was performed to verify the sequencing results. Results:Compared with Sham group, the number of times they entered the novel arm on days 4, 7 and 14 after surgery were significantly reduced, and the time spent in the novel arm was shortened in SEP group ( P<0.05). Compared with SEP group, the number of times they entered the novel arm on days 4, 7 and 14 after surgery was significantly increased, and the time spent in the novel arm was prolonged in SCFAs+ SEP group ( P<0.05). The results of transcriptomic analysis showed that 438 significantly differentially expressed genes were identified in SCFAs+ SEP group, of which the expression of 175 genes was up-regulated and the expression of 263 genes was down-regulated compared with SEP group. The expression of gamma-aminobutyric acid receptor rho-2 (GABRR2) in the brain tissues was significantly up-regulated in SEP group as compared with Sham group ( P<0.05). Compared with SEP group, the expression of GABRR2 in the brain tissue was significantly down-regulated in SCFAs+ SEP group ( P<0.05). There was no significant difference in the expression of GABRR2 in brain tissues between Sham group and SCFAs+ SEP group ( P>0.05). Conclusions:SCFAs may reduce cognitive dysfunction by down-regulating the expression of GABRR2 in septic mice.
