發(fā)布時(shí)間：2018-05-05 17:57

  本文選題：曲尼司特 + 地塞米松　； 參考：《吉林大學(xué)》2017年碩士論文

【摘要】：目的:病毒性角膜基質(zhì)炎是常見(jiàn)的致盲性眼病,由炎性細(xì)胞浸潤(rùn)導(dǎo)致的免疫炎性反應(yīng)是造成角膜組織損害的主要原因。多聚核苷酸(poly(I:C))作為病毒雙鏈RNA的模擬物,能夠誘導(dǎo)角膜基質(zhì)成纖維細(xì)胞產(chǎn)生多種炎性因子、趨化因子及粘附分子。本研究比較抗過(guò)敏藥曲尼司特(Tranilast)與地塞米松對(duì)Poly(I:C)誘導(dǎo)角膜基質(zhì)成纖維細(xì)胞產(chǎn)生炎性因子的影響及機(jī)制。方法:利用Poly(I:C)、Tranilast和地塞米松對(duì)體外培養(yǎng)人角膜基質(zhì)成纖維細(xì)胞進(jìn)行干預(yù)處理。通過(guò)酶聯(lián)免疫吸附分析(Enzyme-linked immunosorbent analyses,ELISA)檢測(cè)促炎性細(xì)胞因子白細(xì)胞介素-6(interleukin-6,IL-6)、趨化因子白細(xì)胞介素-8(interleukin-8,IL-8)及單核細(xì)胞趨化因子-1(monocyte chemoattractant protein-1,MCP-1)的表達(dá);通過(guò)免疫印跡法(Western blot)檢測(cè)細(xì)胞間粘附分子-1(intercellular adhesion molecule-1,ICAM-1)、血管細(xì)胞粘附分子-1(vascular cell adhesion molecule-1,VCAM-1)以及細(xì)胞內(nèi)絲裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、c-Jun(核轉(zhuǎn)錄因子AP-1的組成成分)及核因子κB(NF-κB)的抑制蛋白IκB-α磷酸化表達(dá)的變化。結(jié)果:Tranilast和地塞米松能夠抑制Poly(I:C)誘導(dǎo)角膜基質(zhì)成纖維細(xì)胞產(chǎn)生IL-6、IL-8、MCP-1、ICAM-1及VCAM-1,二者對(duì)上述炎性因子表達(dá)的抑制作用呈現(xiàn)劑量依賴性。Tranilast能夠抑制細(xì)胞內(nèi)c-Jun和MAPK中氨基端激酶(c-Jun N-terminal kinase,JNK)的磷酸化,而地塞米松則抑制MAPK中胞外信號(hào)調(diào)節(jié)激酶(Extracellular signal-regulated kinase,ERK)、P38、JNK,以及細(xì)胞內(nèi)c-Jun及IκB-α的磷酸化。結(jié)論:Tranilast和地塞米松都能夠抑制Poly(I:C)誘導(dǎo)角膜基質(zhì)成纖維細(xì)胞產(chǎn)生炎性因子、趨化因子及粘附分子。Tranilast的作用機(jī)制涉及對(duì)細(xì)胞內(nèi)Jun-AP-1信號(hào)通路的抑制,而地塞米松則通過(guò)抑制MAPK、AP-1及NF-κB信號(hào)通路而發(fā)揮其作用。因此,盡管作用機(jī)制不同,Tranilast可能與地塞米松類(lèi)似,通過(guò)抑制炎性細(xì)胞對(duì)角膜基質(zhì)的浸潤(rùn),從而抑制病毒性角膜基質(zhì)炎的免疫炎癥反應(yīng)。
[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.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R772.21

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