M型胆碱能受体对脓毒症小鼠巨噬细胞极化过程的调控作用

doi:10.3969/j.issn.1002-1949.2019.05.017

摘要
图/表
参考文献(21)
相关文章 (15)

全文: PDF (1206 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的探索不同M型胆碱能受体对脂多糖诱导的脓毒症小鼠模型调控炎症反应的可能机制。方法 C57雄性小鼠随机分为正常对照组、LPS组、哌仑西平组和AF-DX116组。正常对照组小鼠在实验开始0 h及0.5 h均腹腔注射生理盐水；LPS组、哌仑西平组、AF-DX116组小鼠在实验开始0.5 h均腹腔注射LPS制造小鼠脓毒症模型，分别在实验开始0 h给予生理盐水、选择性M1型胆碱能受体阻滞剂哌仑西平、选择性M2型胆碱能受体阻滞剂AF-DX116预处理。分别在注射LPS后2 h及12 h处死小鼠，获取小鼠肝肺组织，采用流式细胞学技术检测组织巨噬细胞的极化情况；免疫荧光双染法检测巨噬细胞的极化情况；PCR法检测肝肺组织SOCS3基因的表达情况。结果流式细胞学结果提示，与LPS组比较，哌仑西平预处理后脓毒症小鼠肝肺组织M1型巨噬细胞比例降低，在肺脏12 h组（3.00±0.25 vs. 3.98±0.38，P<0.01)、肝脏2 h组（3.50±1.34 vs. 5.20±0.59，P<0.01)及肝脏12 h组（4.50±0.42 vs. 5.54±0.52，P<0.05)中差异有统计学意义；而AF-DX116预处理后，可促进脓毒症小鼠模型巨噬细胞向M1型极化，其中在肺脏2 h组（5.12±1.94 vs. 3.64±0.41，P<0.01）、肺脏12 h组（4.63±1.07 vs. 3.98±0.38，P<0.05）及肝脏12 h组(7.68±1.81 vs. 5.54±0.52，P<0.01)中差异有统计学意义。免疫荧光双染结果提示，哌仑西平预处理组小鼠肝脏及肺脏组织M1型巨噬细胞浸润程度较低，而AF-DX116预处理组小鼠肝肺组织M1型巨噬细胞浸润程度增加。PCR结果提示，与LPS组比较，选择性M1型胆碱能受体阻滞剂哌仑西平预处理可抑制脓毒症小鼠肝肺组织SOCS3分子基因的表达水平（肺脏2 h组, 4.91±0.35 vs. 5.69±0.64, P<0.01），而选择性M2型胆碱能受体阻滞剂AF-DX116预处理则作用相反（肺脏2 h组，6.73±0.11 vs. 5.69±0.64, P<0.05）。结论不同的M型胆碱能受体亚型在巨噬细胞的极化过程中发挥了不同的作用。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	王真
	刘璐
	徐龙薇

关键词 ：脓毒症, 胆碱能受体, 巨噬细胞, 极化, SOCS3

作者简介: 王真(1964-)，女，博士，教授，硕士生导师，主任医师，急诊科主任，E-mail:wangzhen1369@hotmail.com。

引用本文:

王真，刘璐，徐龙薇. M型胆碱能受体对脓毒症小鼠巨噬细胞极化过程的调控作用[J]. 中国急救医学, 2019, 39(5): 480-485.
Wang Zhen, Liu Lu, Xu Long-wei. The influence of muscarinic cholinergic receptor on the polarization of macrophages in septic mice model. Chinese Journal of Critical Care Medicine, 2019, 39(5): 480-485.

链接本文:

http://www.cnemergency.org.cn/CN/10.3969/j.issn.1002-1949.2019.05.017 或 http://www.cnemergency.org.cn/CN/Y2019/V39/I5/480

［1］Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3)［J］. JAMA, 2016, 315(8): 801-810. ［2］Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3)［J］. JAMA, 2016, 315(8): 762-774. ［3］van Vught LA, Wiewel MA, Hoogendijk AJ, et al. The Host Response in Patients with Sepsis Developing Intensive Care Unit-acquired Secondary Infections［J］. Am J Respir Crit Care Med, 2017, 196(4):458-470. ［4］Nolan A, Weiden MD. Trends in sepsis and infection sources in the united states. A population-based study［J］. Ann Am Thorac Soc, 2015, 12(5): 784. ［5］van der Poll T, van de Veerdonk FL, Scicluna BP, et al. The immunopathology of sepsis and potential therapeutic targets［J］. Nat Rev Immunol, 2017, 17(7):407-420. ［6］Gustot T. Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response［J］. Curr Opin Crit Care， 2011, 17(2): 153-159. ［7］Opal SM. The evolution of the understanding of sepsis, infection, and the host response: a brief history［J］. Crit Care Nurs Clin North Am， 2011, 23(1): 1-27.  ［8］Borovikova LV, Ivanova S, Zhang M, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin［J］. Nature， 2000， 405 (6785):458-462. ［9］Kanashiro A, S nego F, Ferreira RG. Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis ［J］. Pharmacol Res, 2017, 117:1-8. ［10］Biswas SK, Chittezhath M, Shalova IN， et al. Macrophage polarization and plasticity in health and disease［J］. Immunol Res， 2012, 53(1-3): 11-24. ［11］Hassan MA, Jensen KD, Butty V, et al. Transcriptional and Linkage Analyses Identify Loci that Mediate the Differential Macrophage Response to Inflammatory Stimuli and Infection［J］. PloS Genet, 2015, 11(10):e1 005 619. ［12］Kawashima K, Fujii T, Moriwaki Y, et al. Critical roles of acetylcholine and the muscarinic and nicotinic acetylcholine receptors in the regulation of immune function［J］. Life Sci, 2012, 91(21-22): 1027-1032. ［13］Zhang L, Wang CC. Inflammatory response of macrophages in infection［J］.Hepatobiliary Pancreat Dis Int, 2014,13(2):138-152. ［14］Martinez FO, Gordon S.The M1 and M2 paradigm of macrophage activation: time for reassessment［J］. Prime Rep, 2014, 6:13. ［15］Arora S, Dev K, Agarwal B, et al.Macrophages: Their role, activation and polarization in pulmonary diseases［J］.Immunobiology, 2018, 223(4-5):383-396. ［16］Sahil M, Ankita S, Vemika C,et al. Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and Confers Protection in Sepsis ［J］. J Biol Chem, 2015, 290(30):18 304-18 314. ［17］Lee HH, Shin JS, Lee WS, et al. Biflorin, Isolated from the Flower Buds of Syzygium aromaticum L. Suppresses LPS-Induced Inflammatory Mediators via STAT1 Inactivation in Macrophages and Protects Mice from Endotoxin Shock［J］. J Nat Prod, 2016. 79(4):711-720. ［18］Yoshimura A, Naka T, Kubo M. SOCS proteins, cytokine signalling and immune regulation［J］. Nat Rev Immunol, 2007, 7(6): 454-465. ［19］Dalpke A, Heeg K, Bartz H, et al. Regulation of innate immunity by suppressor of cytokine signaling (SOCS) proteins［J］. Immunobiology, 2008, 213(3-4): 225-235. ［20］Liu Y, Stewart KN, Bishop E, et al. Unique expression of suppressor of cytokine signaling 3 is essential for classical macrophage activation in rodents in vitro and in vivo ［J］. J Immunol, 2008, 180(9): 6270-6278. ［21］Gordon P, Okai B, Hoare JI, et al. SOCS3 is a modulator of human macrophage phagocytosis［J］.J Leukoc Biol, 2016, 100(4):771-780.