中国医科大学学报

中国医科大学学报

中国医科大学学报 ›› 2013, Vol. 42 ›› Issue (10): 903–906.

• 论著 • 上一篇    下一篇

甘珀酸对EAE小鼠IL-12、IL-23的影响

孙叶飞1,张旭2,曲慧玲3,李恩东4,赵传胜3   

  1. 1.中国医科大学附属第一医院胃肠外科,沈阳 110001;
    2.中国医科大学解剖教研室,沈阳 110001;
    3.中国医科大学附属第一医院神经内科,沈阳 110001;
    4.日本名古屋大学大学院神经免疫,名古屋450-0002,日本
  • 收稿日期:2013-06-25 修回日期:2013-11-26 出版日期:2013-10-18 发布日期:2013-11-26
  • 作者简介:孙叶飞(1978-),女,主管护师.

Effects of Carbenoxolone on the Expressions of IL-12 and IL-23 in EAE Mice

SUN Ye-fei1, ZHANG Xu2, QU Hui-ling3, LI En-dong4, ZHAO Chuan-sheng3   

  1. 1. Department of General Surgery, Gastrointestinal Surgery, The First Hospital, China Medical University, Shenyang 110001, China;
    2.Department of Anatomy, China Medical University, Shenyang 110001, China;
    3.Department of Neurology, The First Hospital, China Medical University, Shenyang 110001, China;
    4.Department of Psychoneuroimmunology, Nagoya University, Nagoya 450-0002, Japan
  • Received:2013-06-25 Revised:2013-11-26 Online:2013-10-18 Published:2013-11-26

摘要: 目的 探讨甘珀酸(CBX)对小鼠实验性自身免疫性脑脊髓炎(EAE)IL-12、IL-23的影响。方法 制作小鼠EAE模型后,然后将CBX(20mg/kg)或生理盐水隔日1次静脉注射,比1较各组行为学变化。小胶质细胞与树突细胞与阶梯浓度的CBX共培养后,用RT-PCR检测IL-12IL-23mRNA的表达。用ELISA检测IL-12与IL-23水平。结果 CBX组和EAE组比较,行为学表现有所好转(P<0.05)。体外实验证实与LPS组比较,CBX组小胶质细胞及树突细胞IL-23p19的表达降低(P<0.05),同时CBX处理后能够抑制小胶质细胞IL-23水平(P<0.05)。结论 CBX可通过抑制小胶质细胞或树突细胞IL-23的表达,改善多发性硬化的临床症状。

关键词: 甘珀酸, 多发性硬化, IL-12, IL-23

Abstract: Objective To investigate the effects of Carbenoxolone on IL-12 and IL-23 expression in EAE mice. Methods The EAE models were established using MOG35-55, and theen the mice were intravenously administered with CBX (20 mg/kg) or vehicle control (saline) every other day with the first dose on the day of immunization. The changes of behavioral changes were recorded. Microglia and dendritic cells were incubated with 1ug/ml LPS in the presence of a graded concentration of CBX for 24 h. The IL-12 mRNA and IL-23 mRNA expressions were detected by semiquantitative RT-PCR. Supernatants were collected after an additional 24 h culture for ELISA, and IL-12 and IL-23 levels were measured . Results Behavioral changes in CBX group were improved compared with EAE group(P< 0.05). CBX negatively regulated the expressions of IL-23 p19 in microglia and dendritic cells. IL-23 production by microglia was decreased in CBX group. Conclusion The level of IL-23 in microglia and dendritic cells was negatively regulated by CBX, and CBX can improve the multiple sclerosis clinical symptoms.

Key words: carbenoxolone, multiple sclerosis, IL-12, IL-23

中图分类号: 

  • R741
[1] 朱颖, 刘鹤南, 张朝东. 血清维生素B12水平与多发性硬化关系的Meta分析[J].中国医科大学学报,2010, 39(3):234-237.
[2] Shijie J, Takeuchi H, Yawata I, et al. Blockade of glutamate release from microglia attenuates experimental autoimmune encephalomyelitis in mice[J]. Tohoku J Exp Med ,2009,217(2):87-92.
[3] Taylor AW, Kitaichi N. The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) therapy[J]. Brain Behav Immun, 2008,22(5):639-646.
[4] Baxter AG. The origin and application of experimental autoimmune encephalomyelitis[J]. Nat Rev Immunol ,2007,7(11):904-912.
[5] Takeuchi H, Jin S, Wang J, et al. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner[J]. J Biol Chem ,2006,281(30):21362-21368.
[6] Dutta R, Trapp BD. Pathogenesis of axonal and neuronal damage in multiple sclerosis[J]. Neurology ,2007,68(22 Suppl 3) S22-31: discussion S43-54.
[7] Takeuchi H, Jin S, Suzuki H, et al. Blockade of microglial glutamate release protects against ischemic brain injury[J]. Exp Neurol ,2008,214(1):144-146.
[8] Ma D, Jin S, Li E, et al. The neurotoxic effect of astrocytes activated with toll-like receptor ligands[J]. J Neuroimmunol, 2013,254(1-2):10-18.
[9] Chanson M, Derouette JP, Roth I, et al. Gap junctional communication in tissue inflammation and repair[J]. Biochim Biophys Acta ,2005,1711(2):197-207.
[10] Saez JC, Retamal MA, Basilio D, et al. Connexin-based gap junction hemichannels: gating mechanisms[J]. Biochim Biophys Acta ,2005,1711(2):215-224.
[11] Li E, Noda M, Doi Y, et al. The neuroprotective effects of milk fat globule-EGF factor 8 against oligomeric amyloid beta toxicity[J]. J Neuroinflammation ,2012,9:148.
[12] Endong L, Shijie J, Sonobe Y, et al. The gap-junction inhibitor carbenoxolone suppresses the differentiation of Th17 cells through inhibition of IL-23 expression in antigen presenting cells[J]. J Neuroimmunol ,2011,240-241:58-64.
[13] Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain[J]. Nature ,2003,421(6924):744-748.
[14] Sandeep TC, Yau JL, MacLullich AM, et al. 11 Beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics[J]. Proc Natl Acad Sci U S A ,2004,101(17):6734-6739.
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[2] 卜跃华,解芳. 脑脊液IL-17和IL-23检测在诊断细菌性脑膜炎中的意义[J]. 中国医科大学学报, 2012, 41(5): 474-475.
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