曲尼司特与地塞米松对多聚核苷酸（poly（I：C））诱导角膜基质细胞产生炎性因子的影响及机制研究

发布时间：2018-05-05 17:57

本文选题：曲尼司特 + 地塞米松　；参考：《吉林大学》2017年硕士论文

【摘要】：目的:病毒性角膜基质炎是常见的致盲性眼病,由炎性细胞浸润导致的免疫炎性反应是造成角膜组织损害的主要原因。多聚核苷酸(poly(I:C))作为病毒双链RNA的模拟物,能够诱导角膜基质成纤维细胞产生多种炎性因子、趋化因子及粘附分子。本研究比较抗过敏药曲尼司特(Tranilast)与地塞米松对Poly(I:C)诱导角膜基质成纤维细胞产生炎性因子的影响及机制。方法:利用Poly(I:C)、Tranilast和地塞米松对体外培养人角膜基质成纤维细胞进行干预处理。通过酶联免疫吸附分析(Enzyme-linked immunosorbent analyses,ELISA)检测促炎性细胞因子白细胞介素-6(interleukin-6,IL-6)、趋化因子白细胞介素-8(interleukin-8,IL-8)及单核细胞趋化因子-1(monocyte chemoattractant protein-1,MCP-1)的表达;通过免疫印迹法(Western blot)检测细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)、血管细胞粘附分子-1(vascular cell adhesion molecule-1,VCAM-1)以及细胞内丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、c-Jun(核转录因子AP-1的组成成分)及核因子κB(NF-κB)的抑制蛋白IκB-α磷酸化表达的变化。结果:Tranilast和地塞米松能够抑制Poly(I:C)诱导角膜基质成纤维细胞产生IL-6、IL-8、MCP-1、ICAM-1及VCAM-1,二者对上述炎性因子表达的抑制作用呈现剂量依赖性。Tranilast能够抑制细胞内c-Jun和MAPK中氨基端激酶(c-Jun N-terminal kinase,JNK)的磷酸化,而地塞米松则抑制MAPK中胞外信号调节激酶(Extracellular signal-regulated kinase,ERK)、P38、JNK,以及细胞内c-Jun及IκB-α的磷酸化。结论:Tranilast和地塞米松都能够抑制Poly(I:C)诱导角膜基质成纤维细胞产生炎性因子、趋化因子及粘附分子。Tranilast的作用机制涉及对细胞内Jun-AP-1信号通路的抑制,而地塞米松则通过抑制MAPK、AP-1及NF-κB信号通路而发挥其作用。因此,尽管作用机制不同,Tranilast可能与地塞米松类似,通过抑制炎性细胞对角膜基质的浸润,从而抑制病毒性角膜基质炎的免疫炎症反应。
[Abstract]:Objective: viral keratokeratitis is a common blinding eye disease. Inflammatory response caused by inflammatory cell infiltration is the main cause of corneal tissue damage. Polynucleotide (poly (I:C)) can be used as a simulator of viral double stranded RNA, which can induce corneal stroma fibroblast to produce a variety of inflammatory factors, chemokines and adhesiveness This study compared the effect and mechanism of antiallergic drug Tranilast and dexamethasone on Poly (I:C) induced inflammatory factors in corneal stromal fibroblasts. Methods: Poly (I:C), Tranilast and dexamethasone were used to intervene in cultured human corneal stromal fibroblasts in vitro. Enzyme linked immunosorbent assay (Enzyme). -linked immunosorbent analyses, ELISA) detection of the proinflammatory cytokines interleukin -6 (interleukin-6, IL-6), the expression of chemokine interleukin -8 (interleukin-8, IL-8) and monocyte chemokine -1 (monocyte), and the detection of intercellular adhesion molecules by Western blotting. Tercellular adhesion molecule-1, ICAM-1), vascular cell adhesion molecule -1 (vascular cell adhesion molecule-1, VCAM-1), and intracellular mitogen activated protein kinase (mitogen-activated protein), and the inhibitory protein of nuclear factor kappa inhibitor Results: Tranilast and dexamethasone can inhibit Poly (I:C) induced corneal stroma fibroblasts to produce IL-6, IL-8, MCP-1, ICAM-1 and VCAM-1. The inhibitory effect of two on the expression of the above inflammatory factors is dose-dependent.Tranilast can inhibit the phosphorylation of amino terminal kinase in c-Jun and MAPK. And dexamethasone inhibits the phosphorylation of extracellular signal regulated kinase (Extracellular signal-regulated kinase, ERK), P38, JNK, and intracellular c-Jun and I kappa B- alpha in MAPK. Conclusion: Tranilast and dexamethasone can inhibit the induction of inflammatory factors, chemokines and adhesion molecules induced by the corneal stroma fibroblasts. The mechanism of action involves inhibition of intracellular Jun-AP-1 signaling pathway, while dexamethasone plays its role by inhibiting MAPK, AP-1 and NF- kappa B signaling pathways. Therefore, although the mechanism of action is different, Tranilast may be similar to dexamethasone by inhibiting the infiltration of inflammatory cells to the cornea, thus inhibiting the immunity of viral keratostroma Pestilence and inflammation.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R772.21

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