Effects and mechanism of shikonin on neuroinflammation in sepsis-associated encephalopathy rats
- VernacularTitle:紫草素对脓毒症相关性脑病大鼠神经炎症的影响及机制研究
- Author:
Dalei FENG
1
;
Zhao WANG
1
;
Yingying YANG
2
;
Lei YANG
3
Author Information
1. Dept. of Critical Care Medicine，the First People’s Hospital of Zunyi，Guizhou Zunyi 563000，China
2. Dept. of Oncology，the First People’s Hospital of Zunyi，Guizhou Zunyi 563000，China
3. Dept. of Pediatric Intensive Care Medicine，the First People’s Hospital of Zunyi，Guizhou Zunyi 563000，China
- Publication Type:Journal Article
- Keywords:
shikonin;
sepsis-associated encephalopathy
- From:
China Pharmacy
2024;35(21):2640-2645
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effect and possible mechanism of shikonin on neuroinflammation in sepsis- associated encephalopathy （SAE） rats by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS）-stimulator of interferon gene （STING） signaling pathway. METHODS Rats were randomly separated into SAE group， shikonin low-dose， medium-dose and high-dose groups （1.33， 2.66， 5.32 mg/kg）， high dose of shikonin+Roc A group （5.32 mg/kg shikonin+0.67 mg/kg cGAS-STING signaling pathway activator Roc A）， and control group， with 12 rats in each group. Except for the control group， SAE models were constructed in all other groups. After successful modeling， administration began once a day for 14 days. After administration， the Y-maze experiment and open-field experiment were applied to evaluate the learning and memory ability and anxiety state of rats， respectively. The pathological changes of neurons in the dentate gyrus （DG） of the hippocampus were observed. The number of CD86 and CD206 positive cells， the levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-4 and IL-10， and the protein expressions of cGAS and STING were detected in the brain tissue of the hippocampus DG region. RESULTS Compared with the SAE group， the neuronal damage of rats in shikonin low-dose， medium-dose and high-dose groups were improved； the percentage of activity distance in the “new arm”， the duration of stay in the central area， walking distance， the number of intact neurons and CD206 positive cells in the brain tissue of the hippocampal DG area， and the levels of IL-4 and IL-10 increased/rised/prolonged significantly （P＜0.05）； the number of CD86 positive cells in the brain tissue of the hippocampal DG region， the levels of IL-1β and TNF-α， and protein expressions of cGAS and STING were significantly reduced/decreased/down-regulated （P＜0.05）， and the effect of shikonin was dose-dependent （P＜0.05）. Roc A could significantly reverse the improvement effect of high-dose shikonin on neuroinflammation in SAE rats （P＜0.05）. CONCLUSIONS Shikonin can improve neuroinflammation in SAE rats by inhibiting cGAS-STING signaling pathway.
