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| Effects of Dexmedetomidine on Inflammatory Injury in Burned Rats by Regulating the cGAS-STING Signaling Pathway |
| WU Yi, YAN Yuqiang, SU Rui |
| Xi'an Central Hospital, Shaanxi Xi'an 710003, China |
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Abstract Objective: To investigate the effects of dexmedetomidine (DEX) on inflammatory injury in burned rats by regulating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Methods: Rats were randomly divided into six groups: control group (Control), model group (Model), low dose, medium and high dose DEX groups (DEX-L, DEX-M, DEX-H), and DEX-H + cGAS-STING pathway activator group (DEX-H+DMXAA), with 12 rats in each group. Except for the Control group, all rats were subjected to deep second-degree burns using a burn injury device. The DEX-L, DEX-M, and DEX-H groups received 1, 3, and 5 μg·kg-1·h-1 DEX for 4 hours, respectively. The DEX-H+DMXAA group was administered 25 mg/kg DMXAA and 5 μg·kg-1·h-1 DEX for 4 hours. The Control and Model groups received equivalent amounts of 0.9% saline for 4 hours daily for two weeks. After the intervention, wound healing rates were calculated, serum levels of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA, and histopathological injury scores were assessed by HE staining. Apoptosis in wound tissues was evaluated by TUNEL staining. The expression of cGAS and STING mRNA in wound tissues was measured by qRT-PCR, while apoptosis-related proteins (Bax, Bcl-2) and cGAS-STING pathway proteins were detected by Western blot. Results: Compared with the Control group, the Model group showed significantly higher levels of TNF-α, IL-1β, wound tissue apoptosis rate, cGAS, STING mRNA, and Bax, cGAS, STING, IRF3 protein expression, while Bcl-2 expression decreased (P<0.05). Compared with the Model group, the DEX-L, DEX-M, and DEX-H groups had significantly increased wound healing rates, higher histopathological scores, elevated Bcl-2 expression, and reduced TNF-α, IL-1β levels, wound tissue apoptosis rate, cGAS, STING mRNA, and Bax, cGAS, STING, and IRF3 protein expression, with statistically significant differences between the dosage groups (P<0.05). In the DEX-H+DMXAA group, wound healing rates, histopathological scores, and Bcl-2 expression were lower, while TNF-α, IL-1β levels, wound tissue apoptosis rate, cGAS, STING mRNA, and Bax, cGAS, STING, and IRF3 protein expression were higher compared with the DEX-H group (P<0.05). Conclusion: DEX has anti-inflammatory effects, reduces cell apoptosis, and promotes wound healing in burned rats, and its mechanism may be related to inhibiting the activation of the cGAS-STING signaling pathway.
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2024, Vol. 30 
