Full
Outline
The structural and functional homeostasis of the intestinal barrier plays a key role in the occurrence and progression of sepsis. As a highly selective α2-adrenergic receptor agonist, dexmedetomidine is widely used for sedation in sepsis and perioperative periods requiring surgical intervention. Recent studies have shown that it also exerts anti-inflammatory effects; however, whether it can improve acute intestinal barrier injury in sepsis and the underlying mechanism remain unclear. In this study, an acute sepsis mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). Evans blue staining, transmission electron microscopy, HE staining, ELISA, and RT-PCR were used to observe the effects of dexmedetomidine (1-6 μg·kg-1) on intestinal inflammation and barrier function in septic mice. The expression changes of α2-adrenergic receptors during inflammation, as well as the effects of dexmedetomidine on NF-κB and RhoA/ROCK signaling pathways under LPS stimulation, were further evaluated in mouse intestinal tissues and RAW 264.7 macrophages. The results showed that dexmedetomidine (1-6 μg·kg-1) administered 6 h after LPS stimulation significantly reduced the levels of inflammatory factors in plasma and intestinal tissues of septic mice, improved intestinal barrier function, and upregulated the expression of tight junction proteins in the small intestine and colon. LPS stimulation downregulated the expression of α2-adrenergic receptors on macrophages in vivo and in vitro, whereas dexmedetomidine (5-20 nmol·L-1) reversed this downregulation under inflammatory conditions, inhibited NF-κB pathway activation and inflammatory cytokine secretion in RAW 264.7 cells, and antagonized RhoA/ROCK pathway activation and decreased transepithelial electrical resistance in Caco-2 cells. In conclusion, this study demonstrates that LPS stimulation downregulates α2-adrenergic receptor expression in macrophages, and dexmedetomidine can upregulate α2-adrenergic receptors, thereby it may inhibit the NF-κB and RhoA/ROCK pathways, ultimately suppressing inflammation, improving intestinal barrier function, and alleviating acute intestinal barrier injury in sepsis. The animal experiments were approved by the Animal Ethics Committee of Southwest University (Ethics Review No.: IACUC-20260305-12).
271
121
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
关闭全屏
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
