Peng Ji, Zhang Peng, Zheng Han, Ren Yun-Qin, Yan Hong
Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing 400042, China.
Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing 400042, China.
Chin J Traumatol. 2019 Jun;22(3):161-165. doi: 10.1016/j.cjtee.2019.03.002. Epub 2019 Apr 13.
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.
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.
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).
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.
探讨右美托咪定（Dex）是否可通过抑制海马小胶质细胞中NLRP3炎性小体的激活来减少炎性因子IL-1β的产生，从而减轻手术创伤诱导的中枢神经系统炎性反应。
本研究采用开腹探查术建立实验模型。将48只雄性Sprague Dawley大鼠随机分为4组（每组n = 12），分别为假手术对照组（A组）、单纯开腹手术组（B组）；以及5 μg/kg（D1组）或10 μg/kg（D2组）不同剂量Dex治疗组。D1组和D2组大鼠每6小时腹腔注射相应剂量的Dex。术后12小时处死大鼠；分离海马组织并制作冰冻切片。通过免疫组织化学评估小胶质细胞的激活情况。通过免疫印迹法检测NLRP3、半胱天冬酶-1、凋亡相关斑点样蛋白（ASC）和IL-1β的蛋白表达。所有数据均以均数±标准差表示，采用独立样本t检验分析组间统计学差异。
开腹手术后大鼠海马中活化的小胶质细胞显著增加（B组与假手术对照组相比，p < 0.01）。Dex治疗后，其数量呈剂量依赖性减少（D1组与D2组相比，p < 0.05），然而两组中活化的小胶质细胞仍高于假手术对照组（均p < 0.05）。进一步的蛋白质印迹分析表明，开腹手术组海马中NLRP3、半胱天冬酶-1、ASC及下游细胞因子IL-1β的蛋白表达水平显著高于假手术对照组（均p < 0.01）。Dex治疗后这些蛋白的表达升高得到缓解，同样呈剂量依赖性（D2组与D1组相比，p < 0.05）。
Dex可抑制大鼠术后海马中小胶质细胞和NLRP3炎性小体的激活，并且使用Dex还可使IL-1β的合成和分泌呈剂量依赖性减少。因此，Dex可减轻手术创伤诱导的中枢神经系统炎症激活。
