L161982对大鼠实验性自身免疫性神经炎中巨噬细胞亚型变化的影响

doi:10.6040/j.issn.1671-7554.0.2015.068

摘要/Abstract

摘要： 目的探讨前列腺素E₂-EP4受体拮抗剂L161982对大鼠实验性自身免疫性神经炎(EAN)中巨噬细胞亚型的影响。方法 EAN模型建立后将21只EAN大鼠随机分为A、B、C 3组。A组每日腹腔注射L161982溶媒,B组自免疫前1天至免疫第8天(免疫阶段)、C组自免疫第5~16天(发病期)均每日腹腔注射L161982(5 mg/kg)。免疫第16天处死大鼠收集腹腔灌洗细胞,用CD68与CD86或CD163不同荧光抗体组合标记M1、M2亚型巨噬细胞,流式细胞术检测各组巨噬细胞亚群比例;ELISA法检测各组大鼠脾单核细胞培养上清中IL-12、IL-10含量。结果 B、C组与A组相比,L161982降低CD86+细胞占总细胞的比例(P<0.05)及CD86+细胞占CD68+细胞比例(P<0.05),升高CD163+细胞占CD68+细胞比例(P<0.05);降低IL-12含量(P<0.05),升高IL-10含量(P<0.05)。B组高峰期临床评分较A、C组降低(P<0.05)。结论 L161982通过降低EAN中M1型巨噬细胞比例,升高M2型巨噬细胞比例减轻EAN病情,免疫阶段作用更明显。

关键词: 实验性自身免疫性神经炎, L161982, 巨噬细胞, 细胞因子

Abstract: Objective To explore the effects of L161982, one prostaglandin E₂-EP4 receptor antagonist, on macrophage subtypes in experimental autoimmune neuritis (EAN). Methods After 21 EAN models were established, they were randomly divided into group A, B and C. Rats in group A were intraperitoneally injected with 5 mg/kg L161982 dissolvent daily, rats in group B received the same volume from one day before immunization to the eighth day after immunization (immunization phase), and rats in group C received the same volume from the fifth to sixteenth day after immunization (onset phase). All rats were sacrificed on the sixteenth day after immunization. The infiltrated macrophages were concentrated in the lavage fluid of peritoneal exudates. The type M1 and M2 macrophages were identified using CD68 and CD86, or CD163 fluorescent antibodies, and measured with flow cytometry. The levels of IL-12 and 1L-10 in the single cell suspensions of mononuclear cells of spleen were measured with ELISA. Results Compared with group A, Group B and C had decreased percentage of CD68+ cells of total cells, increased percentage of CD163+ cells of CD68+ cells (P<0.05), decreased level of IL-12 (P<0.05), and increased level of IL-10 (P<0.05). Group B had decreased peak clinical score compared with group A and C (P<0.05). Conclusion L161982 attenuates EAN by contributing to the shift from M1 to M2 macrophages. The immunization phase has a more significant therapeutic effect.

Key words: Experimental autoimmune neuritis, Cytokine, Macrophages, L161982

中图分类号:

R745.4

冯青, 谭晓冬. L161982对大鼠实验性自身免疫性神经炎中巨噬细胞亚型变化的影响[J]. 山东大学学报（医学版）, 2015, 53(10): 21-25.

FENG Qing, TAN Xiaodong. L161982 influences macrophage subtypes in rats with experimental autoimmune neuritis[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(10): 21-25.

参考文献

[1] Soliven B. Animal models of autoimmune neuropathy[J]. ILAR J, 2014, 54(3): 282-290.
[2] Aoki T, Narumiya S. Prostaglandins and chronic inflammation[J]. Cell, 2012, 33(6): 304-311.
[3] Shin T, Ahn M, Matsumoto Y, et al. Mechanism of experimental autoimmune neuritis in Lewis rats: the dual role of macrophages[J]. Histol Histopathol, 2013, 28(6): 679-684.
[4] 谭晓冬, 段瑞生, 孙若鹏, 等. 脱氢表雄酮对大鼠实验性自身免疫性神经炎的影响[J]. 山东大学学报: 医学版, 2008, 46(9): 837-841. TAN Xiaodong, DUAN Ruisheng, SUN Ruopeng, et al. Study on protective efficacy of dehydroepiandrosterone in experimental autoimmune neuritis[J]. Journal of Shandong University: Health Sciences, 2008, 46(9): 837-841.
[5] Zhang HL, Hassan MY, Zheng XY, et al. Attenuated EAN in TNF-alpha deficient mice is associated with an altered balance of M1/M2 macrophages[J]. PLoS One, 2012, 7(5): e38157. doi: 10.1371/journal.pone.0038157. Epub 2012 May 30.
[6] Kittan NA, Allen RM, Dhaliwal A, et al. Cytokine induced phenotypic and epigenetic signatures are key to establishing specific macrophage phenotypes[J]. PLoS One, 2013, 8(10): e78045. doi: 10.1371/journal.pone.0078045. eCollection 2013.
[7] Brunn A, Mihelcic M, Carstov M, et al. IL-10, IL-4, and STAT6 promote an M2 milieu required for termination of P0 (106-125)-induced murine experimental autoimmune neuritis[J]. Am J Pathol, 2014, 184(10): 2627-2640.
[8] Dey A, Allen J, Hankey-Giblin PA. Ontogeny and polarization of macrophages in inflammation: blood monocytes versus tissue macrophages[J]. Front Immunol, 2015, 5: 683. doi: 10.3389/fimmu.2014.00683. eCollection 2014.
[9] Schiffmann S, Weigert A, Männich J, et al. PGE2/EP4 signaling in peripheral immune cells promotes development of experimental autoimmune encephalomyelitis[J]. Biochem Pharmacl, 2014, 87(4): 625-635.
[10] Brambilla R, Dvoriantchikova G, Barakat D, et al. Transgenic inhibition of astroglial NF-κB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis[J]. J Neuroinflammation, 2012, 9: 213. doi: 10.1186/1742-2094-9-213.
[11] Zhang HL, Zheng XY, Zhu J. Th1/Th2/Th17/Treg cytokines in Guillain-Barré syndrome and experimental autoimmune neuritis[J]. Cytokine Growth Factor Rev, 2013, 24(5): 443-453.
[12] Tugal D, Liao X, Jain MK, et al. Transcriptional control of macrophage polarization[J]. Arterioscler Thromb Vasc Biol, 2013, 33(6): 1135-1144.
[13] Zhou D, Huang C, Lin Z, et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways[J]. Cell Siqnal, 2014, 26(2): 192-197.
[14] Mikita J, Dubourdieu-Cassagno N, Deloire MS, et al. Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration[J]. Mult Scler, 2011, 17(1): 2-15.
[15] Shin T, Ahn M, Matsumoto Y. Mechanism of experimental autoimmune encephalomyelitis in Lewis rats: recent insights from macrophages[J]. Anat Cell Biol, 2012, 45(3): 141-148.

相关文章 15

[1]	李习平,邱梅,黄瑞峰,林慧慧,刘丝丝,罗鸿莹,王宇月,王敏,杨晓彤. 基于脂质沉积抑制-代谢清除协同效应的黄连素抗动脉粥样硬化机制研究进展[J]. 山东大学学报 (医学版), 2025, 63(9): 77-83.
[2]	张锦涛,董亮. 气道上皮及其源性细胞因子与哮喘:思考与展望[J]. 山东大学学报 (医学版), 2024, 62(5): 1-6.
[3]	吴飞,李清丽,肖振卫. 孟德尔随机化探究细胞因子与慢性肾脏病的因果关系[J]. 山东大学学报 (医学版), 2024, 62(11): 85-95.
[4]	祁少俊,唐延金,张正铎,吴虹,张佳程,秦川,刘锐,高希宝. 补充多种微量元素对高糖饮食大鼠的保护作用[J]. 山东大学学报 (医学版), 2023, 61(7): 19-26.
[5]	郑荣慧,李攀,曹秀琴,贺瑞霞,陈民佳,陈海霞,杨志伟. SQSTM1蛋白在嗜肺军团菌感染RAW264.7细胞自噬中的作用机制[J]. 山东大学学报 (医学版), 2023, 61(6): 10-21.
[6]	王园园,孙云. 合并新型冠状病毒肺炎的维持性血液透析患者死亡危险因素[J]. 山东大学学报 (医学版), 2023, 61(11): 68-73.
[7]	王福立,孙银萍,秦杰,荣建胜. DC-CIK细胞联合EGFR-TKI治疗35例老年晚期EGFR突变肺癌的效果[J]. 山东大学学报 (医学版), 2022, 60(7): 110-117.
[8]	孙丽娜,杜晓晓,张红娟,孟金来. 人类白细胞抗原G调控蜕膜自然杀伤细胞促进滋养细胞侵袭[J]. 山东大学学报 (医学版), 2022, 60(6): 41-45.
[9]	李华玉,时萧寒,张新蕊,李峰. 203例胶质瘤患者睡眠障碍与炎症细胞因子的关联分析[J]. 山东大学学报 (医学版), 2022, 60(12): 26-30.
[10]	张阿敏,李国盛,李福海. 儿童支原体大叶性肺炎肺泡灌洗液细胞因子与局部炎症的相关性[J]. 山东大学学报 (医学版), 2022, 60(11): 82-88.
[11]	葛少华,丁田,刘红蕊. 2型免疫在组织修复中的作用及调控机制[J]. 山东大学学报 (医学版), 2021, 59(9): 51-56.
[12]	周溪,黄霂晗,任玉洁,邱洋. 新型冠状病毒感染与天然免疫及炎症反应[J]. 山东大学学报 (医学版), 2021, 59(5): 15-21.
[13]	张栌丹,丁晓玲,崔舒悦,程晨,魏福兰,丁刚. 牙周膜干细胞调节巨噬细胞功能的体外研究[J]. 山东大学学报 (医学版), 2021, 59(3): 35-40.
[14]	李湘青,殷欣,赵雪莲,赵培庆. NK细胞亚群CD56^bright在帕金森患者外周血中的表达及临床意义[J]. 山东大学学报 (医学版), 2021, 59(2): 34-40.
[15]	杨佳,张曼,陈凯明,曹曦. miR-146a经TLR4/MyD88途径加速巨噬细胞迁移所致动脉硬化的作用机制[J]. 山东大学学报 (医学版), 2021, 59(11): 1-7.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed