本文選題：流感病毒 + 抑制性O(shè)DN�。� 參考：《吉林大學(xué)》2011年博士論文

【摘要】：流感是一種由流感病毒感染引起的具有高度傳染性的呼吸系統(tǒng)疾病,上世紀(jì)3次流感爆發(fā)流行造成了上千萬人死亡,且大多數(shù)為青壯年。普遍認(rèn)為重癥流感的死亡原因與流感病毒誘導(dǎo)的過激性天然免疫反應(yīng)以及大量細(xì)胞因子分泌造成急性肺部炎癥性損傷有密切關(guān)系。因此,抑制過激性免疫應(yīng)答對流感引起的急性肺損傷的防治可能有重要作用。 我們在前期工作中設(shè)計并驗證了一種命名為SAT05f的寡聚脫氧核苷酸(oligodeoxynucleotide, ODN),在體外及小鼠體內(nèi)表現(xiàn)出選擇性抑制TLR7/9活化的作用。為了研究SAT05f是否能夠減輕流感病毒感染引起的小鼠急性肺損傷,我們選擇FM1流感病毒株,以滴鼻的方式感染BALB/c小鼠建立了小鼠急性肺損傷模型。在此基礎(chǔ)上,我們研究了SAT05f對小鼠急性肺損傷的干預(yù)作用。出乎意料的是,SAT05f只表現(xiàn)出輕度減輕肺病理損傷的作用,而作為對TLR7/9只在體外有微弱抑制作用的對照ODN(MS19)卻明顯地減輕了流感病毒引起急性肺組織病理損傷;抑制了小鼠的體重下降,減低了小鼠的死亡率。為了解釋這種現(xiàn)象,我們對小鼠的肺組織中炎性細(xì)胞浸潤、TNF-?和IL-10的表達水平進行了檢測,結(jié)果顯示:MS19能抑制小鼠肺組織中中性粒細(xì)胞浸潤,且肺組織中TNF-?和IL-10的表達水平均降低。這些結(jié)果表明,MS19減輕肺損傷的作用與抑制肺組織炎癥反應(yīng)及TNF-?有關(guān),是否其他機制也參與其中還有待進一步研究。
[Abstract]:Influenza is a highly infectious respiratory disease caused by influenza virus infections. Three outbreaks of influenza in the last century have killed tens of millions of people, mostly young adults. It is generally believed that the causes of death of severe influenza are closely related to the acute pulmonary inflammatory injury induced by influenza virus induced by excessive innate immune response and by the secretion of a large number of cytokines. Therefore, the inhibition of excessive immune response may play an important role in the prevention and treatment of acute lung injury induced by influenza. We have designed and verified a novel oligodeoxynucleotide (ODN) named SAT05f, which can selectively inhibit the activation of TLR7/9 in vitro and in vivo. In order to study whether SAT05f can attenuate the acute lung injury induced by influenza virus infection in mice, we selected FM1 influenza virus strain and infected BALB/c mice by nasal drip to establish an acute lung injury model. On this basis, we studied the effect of SAT05f on acute lung injury in mice. It was not expected that SAT05f showed a slight reduction of lung pathological injury, while the control ODN MS19, which had only a slight inhibitory effect on TLR7/9 in vitro, significantly alleviated the acute lung pathological damage caused by influenza virus. Inhibit the weight loss of mice and reduce the mortality of mice. In order to explain this phenomenon, we treated the infiltration of inflammatory cells in the lung tissue of mice. The expression level of IL-10 was detected. The results showed that WMS19 could inhibit the infiltration of neutrophil in lung tissue of mice, and the expression of TNF-19 in lung tissue of mice. And the expression level of IL-10 was decreased. These results suggest that MS19 can attenuate lung injury and inhibit the inflammatory response of lung tissue and TNF? Whether other mechanisms are also involved remains to be further studied.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R392.1

【共引文獻】

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本文編號：1876364