Ji Peng,Peng Zhang,Han Zheng,Yun-Qin Ren,Hong Yan.[J].中华创伤杂志英文版,2019,22(3):161-165
Dexmedetomidine reduces hippocampal microglia inflammatory response induced by surgical injury through inhibiting NLRP3
  
DOI:
KeyWord: DexmedetomidineHippocampal microgliaInflammasomeIL-1b
FundProject:
Author NameAffiliation
Ji Peng Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing 400042, China 
Peng Zhang Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing 400042, China 
Han Zheng Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing 400042, China 
Yun-Qin Ren Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing 400042, China 
Hong Yan Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing 400042, China 
Hits:
Download times:
Abstract:
      Purpose: To investigate whether dexmedetomidine (Dex) can reduce the production of inflammatory factor IL-1b 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 ¼ 12 for each), respectively sham control (group A), laparotomy only (group B); and Dex treatment with different doses of 5 mg/kg (group D1) or 10 mg/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-1b 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 dosedependent 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-1b 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-1b 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.
View Full Text   View/Add Comment  Download reader
Close