Dexmedetomidine reduces hippocampal microglia inflammatory response induced by surgical injury through inhibiting NLRP3.
10.1016/j.cjtee.2019.03.002
- Author:
Ji PENG
1
;
Peng ZHANG
1
;
Han ZHENG
1
;
Yun-Qin REN
1
;
Hong YAN
2
Author Information
1. Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing 400042, China.
2. Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing 400042, China. Electronic address: cqyanhong@163.com.
- Publication Type:Journal Article
- Keywords:
Dexmedetomidine;
Hippocampal microglia;
IL-1β;
Inflammasome
- MeSH:
Animals;
Dexmedetomidine;
administration & dosage;
pharmacology;
Dose-Response Relationship, Drug;
Hippocampus;
metabolism;
Immunohistochemistry;
Inflammasomes;
metabolism;
Inflammation Mediators;
metabolism;
Injections, Intraperitoneal;
Interleukin-1beta;
metabolism;
Laparotomy;
adverse effects;
Male;
Microglia;
metabolism;
NLR Family, Pyrin Domain-Containing 3 Protein;
metabolism;
Rats, Sprague-Dawley;
Time Factors
- From:
Chinese Journal of Traumatology
2019;22(3):161-165
- CountryChina
- Language:English
-
Abstract:
PURPOSE:To investigate whether dexmedetomidine (Dex) can reduce the production of inflammatory factor IL-1β by inhibiting the activation of NLRP3 inflammasome in hippocampal microglia, thereby alleviating the inflammatory response of the central nervous system induced by surgical injury.
METHODS:Exploratory laparotomy was used in experimental models in this study. Totally 48 Sprague Dawley male rats were randomly divided into 4 groups (n = 12 for each), respectively sham control (group A), laparotomy only (group B); and Dex treatment with different doses of 5 μg/kg (group D1) or 10 μg/kg (group D2). Rats in groups D1 and D2 were intraperitoneally injected with corresponding doses of Dex every 6 h. The rats were sacrificed 12 h after operation; the hippocampus tissues were isolated, and frozen sections were made. The microglia activation was estimated by immunohistochemistry. The protein expression of NLRP3, caspase-1, ASC and IL-1β were detected by immunoblotting. All data were presented as mean ± standard deviation, and independent sample t test was used to analyze the statistical difference between groups.
RESULTS:The activated microglia in the hippocampus of the rats significantly increased after laparotomy (group B vs. sham control, p < 0.01). After Dex treatment, the number was decreased in a dose-dependent way (group D1 vs. D2, p < 0.05), however the activated microglia in both groups were still higher than that of sham controls (both p < 0.05). Further Western blot analysis showed that the protein expression levels of NLRP3, caspase-1, ASC and downstream cytokine IL-1β in the hippocampus from the laparotomy group were significantly higher than those of the sham control group (all p < 0.01). The elevated expression of these proteins was relieved after Dex treatment, also in a dose-dependent way (D2 vs. D1 group, p < 0.05).
CONCLUSION:Dex can inhibit the activation of microglia and NLRP3 inflammasome in the hippocampus of rats after operation, and the synthesis and secretion of IL-1β are also reduced in a dose-dependent manner by using Dex. Hence, Dex can alleviate inflammation activation on the central nervous system induced by surgical injury.
