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.

相关文章 15

[1]	张士宝刘庆勇阮喜云陈杰张建军李宗武杨广笑王全颖. NT₄-SAC-HA₂-TAT融合基因表达载体的构建及鉴定[J]. 山东大学学报(医学版), 2209, 47(6): 15-19.
[2]	鹿向东杨伟徐广明曲元明. 脑膜瘤中PPAR-γ的表达及曲格列酮对脑膜瘤培养细胞生长的影响[J]. 山东大学学报(医学版), 2209, 47(6): 65-.
[3]	徐宁宇王磊郝恩魁苏国海. STEMI患者急诊PCI前口服阿托伐他汀对炎症介质及左心室功能的影响[J]. 山东大学学报(医学版), 2209, 47(6): 69-72.
[4]	郝跃伟刘雪平赵婷婷郑敏王一兵. 环氧化酶2基因多态性与动脉粥样硬化缺血性脑卒中的相关性[J]. 山东大学学报(医学版), 2209, 47(6): 95-98.
[5]	张亮,徐敏,庄向华,娄福臣,娄能俊,吕丽,郭文娟,郑凤杰,陈诗鸿. 内质网应激与凋亡在糖尿病周围神经病变中的表达变化[J]. 山东大学学报（医学版）, 2017, 55(8): 13-17.
[6]	张栾,陈欧,栾云,朱晓波,陈元,王一彪. Gemigliptin对野百合碱诱导的肺动脉高压大鼠治疗作用及炎症因子的影响[J]. 山东大学学报（医学版）, 2017, 55(5): 19-22.
[7]	李睿,马伟红,任满意,赵萌萌,姜珊,巨媛媛,郭颖,孙昭辉,隋树建. TWEAK与原发性高血压患者心脏重塑的相关性[J]. 山东大学学报（医学版）, 2017, 55(5): 49-55.
[8]	闫松鹤,高立芬,赵伟,王燕. 人牙根尖乳头细胞抑制人单核细胞THP-1活化及其分子机制[J]. 山东大学学报（医学版）, 2017, 55(3): 49-53.
[9]	郭贺贺,孙志强,刘艳娟,刘奕晨,李广,郑方. 去甲斑蝥素对骨髓瘤U266细胞Notch信号通路表达的影响[J]. 山东大学学报（医学版）, 2017, 55(3): 32-37.
[10]	涂云华,陈利远,王喜,周英,康颖倩,薛月萃,荣冬芸,叶振源,曹煜. 芳姜黄酮衍生物对WM35细胞增殖及凋亡的影响[J]. 山东大学学报（医学版）, 2017, 55(2): 68-73.
[11]	吴倩,倪阳,杨清锐,孙红胜. 双眼睑肿胀及双侧颌下包块1例——IgG4相关性疾病的诊断与思考[J]. 山东大学学报（医学版）, 2017, 55(11): 93-96.
[12]	巩璐伟,周丽珍,苏国海. 培哚普利通过调节Akt-FoxO1通路保护糖尿病性心肌病大鼠心功能损伤[J]. 山东大学学报（医学版）, 2017, 55(10): 65-70.
[13]	赵路,矫俊,张腾,焦薪霖,崔保霞. 肝X受体在卵巢癌组织中的表达及T0901317在卵巢癌细胞系SKOV3中的作用[J]. 山东大学学报（医学版）, 2017, 55(1): 49-53.
[14]	杨延军,梁静,李芳,杜令席. 常山酮对小鼠子宫内膜异位症巨噬细胞极化的调控作用[J]. 山东大学学报（医学版）, 2016, 54(9): 26-31.
[15]	张琨,张孝国,崔杏杏,陈士俊. 慢性HBV感染者外周血单个核细胞凋亡相关因子的表达及其与乙肝慢性化的关系[J]. 山东大学学报（医学版）, 2016, 54(7): 38-42.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed