利多卡因对脂多糖诱导小鼠巨噬细胞caspase-1和IL-1β表达的影响

doi:10.6040/j.issn.1671-7554.0.2015.268

摘要/Abstract

摘要： 目的观察利多卡因对脂多糖诱导小鼠巨噬细胞凋亡、含半胱氨酸的天冬氨酸蛋白水解酶-1(caspase-1)和白细胞介素-1β(IL-1β)表达的影响,探讨利多卡因在脂多糖诱导相关炎症保护作用的机制。方法将单层培养于6孔板的小鼠巨噬细胞随机分为对照组、利多卡因组、脂多糖组和利多卡因+脂多糖组。采用流式细胞术测定细胞凋亡率,RT-PCR法检测细胞中caspase-1和IL-1β的mRNA表达水平,ELISA法检测培养液中caspase-1和IL-1β的蛋白浓度。结果与对照组相比,利多卡因组细胞凋亡率、caspase-1和IL-1β的mRNA表达及蛋白表达无明显变化(P>0.05),脂多糖组细胞凋亡率显著增高(P<0.05),caspase-1和IL-1β的mRNA表达水平以及蛋白表达水平显著增高(P<0.05);利多卡因+脂多糖组与脂多糖组相比细胞凋亡率显著降低(P<0.05),caspase-1和IL-1β的mRNA表达水平以及蛋白表达水平显著降低(P<0.05)。结论利多卡因预处理可抑制脂多糖诱导小鼠巨噬细胞的凋亡和caspase-1、IL-1β过表达。利多卡因抗炎作用可能与抑制免疫细胞凋亡、减少炎性因子释放有关。

关键词: 利多卡因, 脂多糖, 白细胞介素-1&beta, 凋亡, 含半胱氨酸的天冬氨酸蛋白水解酶-1, 炎症

Abstract: Objective To observe the protective effect of lidocaine on cysteinyl aspartate specific proteinase-1(caspase-1) and interleukin-1β (IL-1β) in lipopolysaccharide-induced inflammation in mice and to investigate its mechanism. Methods Monolayer cultured mouse macrophages in six-well plates were randomly divided into 4 groups:control group, lidocaine group, lipopolysaccharide group, and lidocaine+lipopolysaccharide group. Cell apoptosis rate was measured with flow cytometry. Expressions of caspase-1 and IL-1β mRNA were detected with realtime PCR (RT-PCR). The protein concentrations of caspase-1 and IL-1β in the culture medium were assessed with enzyme-linked immunosorbent assay (ELISA). Results Compared with control group, in lidocaine group, the apoptosis rate, mRNA expression and protein expression of caspase-1 and IL-1β had no significant change (P>0.05); in the lipopolysaccharide group, the apoptosis rate, mRNA expression and protein expression of caspase-1 and IL-1β were significantly higher (all P<0.05). Compared with the lipopolysaccharide group, in lidocaine+lipopolysaccharide group, apoptosis was significantly reduced (P<0.05), mRNA and protein expression levels of caspase-1 and IL-1β expressions were markedly lower (P<0.05). Conclusion Lidocaine can reduce apoptosis in murine macrophages lipopolysaccharide-induced inflammatory response. Protective effects of lidocaine on tissue inflammation may be related to inhibition ofcaspase-1 and IL-1β.

Key words: Lidocaine, Lipopolysaccharides, Cysteinyl aspartate specific proteinase-1, Interleukin-1β, Inflammation, Apoptosis

中图分类号:

R364.5

刘洋, 王焕亮, 刘亚洋, 闫红丹, 孙宝柱, 黄珊珊, 黄瑞, 类维富. 利多卡因对脂多糖诱导小鼠巨噬细胞caspase-1和IL-1β表达的影响[J]. 山东大学学报（医学版）, 2015, 53(12): 43-46,56.

LIU Yang, WANG Huanliang, LIU Yayang, YAN Hongdan, SUN Baozhu, HUANG Shanshan, HUANG Rui, LEI Weifu. Effects of lidocaine on caspase-1 and IL-1β lipopolysaccharide-induced mice macrophages[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(12): 43-46,56.

参考文献

[1] Shalini S, Dorstyn L, Dawar S, et al. Old, new and emerging functions of caspases[J].Cell Death Differ, 2015, 22(4):526-539.
[2] 雷国伟,毛立明,李华,等.炎症小体在对抗微生物感染中的作用[J].中国细胞生物学学报, 2011, 33(12):1301-1315.LEI Guowei, MAO Liming, LI Hua, et al. Function of inflammasomes in anti-microbial infections[J]. Chinese Journal of Cell Biology, 2011, 33(12):1301-1315.
[3] Netea MG, van de Veerdonk FL, van der Meer JW, et al. Inflammasome-Independent Regulation of IL-1-Family Cytokines[J]. Annu Rev Immunol, 2015, 33:49-77. doi:10.1146/annurev-immunol-032414-112306
[4] Barker BR, Taxman DJ, Ting JP. Cross-regulation between the IL-1beta/IL-18 processing inflammasome and other inflammatory cytokines[J]. Curr Opin Immunol, 2011, 23(5):591-597.
[5] Ozaki E, Campbell M, Doyle SL. Targeting the NLRP3 inflammasome in chronic inflammatory diseases:current perspectives[J]. J Inflamm Res, 2015, 8:15-27.doi:10.2147/JIR.S51250
[6] Vance RE. The NAIP/NLRC4 inflammasomes[J]. Curr Opin Immunol, 2015, 32:84-89. doi:10.1016/j.coi.2015.01.010
[7] Martinon F, Burns K, Tschopp J. The inflammasome:a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta[J]. Mol Cell, 2002, 10(2):417-426.
[8] Herminghaus A, Wachowiak M, Wilhelm W, et al. Intravenous administration of lidocaine for perioperative analgesia. Review and recommendations for practical usage[J]. Anaesthesist, 2011, 60(2):152-160.
[9] Wang HL, Zhang WH, Lei WF, et al. The inhibitory effect of lidocaine on the release of high mobility group box 1 in lipopolysaccharide-stimulated macrophages[J]. Anesth Analg, 2011, 112(4):839-844.
[10] 叶婷,类维富,王焕亮,等.利多卡因对LPS诱导巨噬细胞HMGB1释放及转位的影响[J].山东大学学报:医学版, 2010, 48(3):44-47. YE Ting, LEI Weifu, WANG Huanliang, et al. Effects of Lidocaine on the release and translocation of HMGB1 in macrophages induced by lipopolysaccharide[J]. Journal of Shandong University:Health Sciences, 2010, 48(3):44-47.
[11] 周长青,王焕亮,张丽,等.利多卡因对脂多糖诱导的巨噬细胞高迁移率族蛋白B1 mRNA表达的影响[J].临床麻醉学杂志, 2009, 25(9):792-794. ZHOU Changqing, WANG HuanLiang, ZHANG Li, et al. Effects of lidocaine on expression of HMGB1 mRNA induced by lipopolysaccharide in rat peritoneal macrophages[J]. Clin Anesthesiol, 2009, 25(9):792-794.
[12] Nikoletopoulou V, Markaki M, Palikaras K, et al. Crosstalk between apoptosis, necrosis and autophagy[J]. Biochim Biophys Acta, 2013, 1833(12):3448-3459.
[13] Martins JD, Liberal J, Silva A, et al. Autophagy and inflammasome interplay[J]. DNA Cell Biol, 2015, 34(4):274-281.
[14] Ren L, Wang R, Xu T. Three representative subtypes of caspase in miiuy croaker:genomic organization, evolution and immune responses to bacterial challenge[J]. Fish Shellfish Immunol, 2014, 40(1):61-68.
[15] Eltom S, Belvisi MG, Stevenson CS, et al. Role of the inflammasome-caspase1/11-IL-1/18 axis in cigarette smoke driven airway inflammation:an insight into the pathogenesis of COPD[J]. PLoS One, 2014, 9(11):112829.
[16] Peng Y, French BA, Tillman B, et al. The inflammasome in alcoholic hepatitis:Its relationship with Mallory-Denk body formation[J]. Exp Mol Pathol, 2014, 97(2):305-313.

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