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| Ji Peng,Peng Zhang,Han Zheng,Yun-Qin Ren,Hong Yan.[J].Chin J Traumatol,2019,22(3):161-165. [doi] |
| Dexmedetomidine reduces hippocampal microglia inflammatory response induced by surgical injury through inhibiting NLRP3 |
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| DOI： |
| KeyWord: DexmedetomidineHippocampal microgliaInflammasomeIL-1b |
| FundProject: |
| Author Name | Affiliation | | 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 |
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| 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. |
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