寡聚脱氧核苷酸能减轻流感病毒诱导的小鼠急性炎性肺损伤

发布时间：2018-05-12 00:37

本文选题：流感病毒 + 抑制性ODN　；参考：《吉林大学》2011年博士论文

【摘要】：流感是一种由流感病毒感染引起的具有高度传染性的呼吸系统疾病,上世纪3次流感爆发流行造成了上千万人死亡,且大多数为青壮年。普遍认为重症流感的死亡原因与流感病毒诱导的过激性天然免疫反应以及大量细胞因子分泌造成急性肺部炎症性损伤有密切关系。因此,抑制过激性免疫应答对流感引起的急性肺损伤的防治可能有重要作用。我们在前期工作中设计并验证了一种命名为SAT05f的寡聚脱氧核苷酸(oligodeoxynucleotide, ODN),在体外及小鼠体内表现出选择性抑制TLR7/9活化的作用。为了研究SAT05f是否能够减轻流感病毒感染引起的小鼠急性肺损伤,我们选择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损伤模型。在此基础上,我们研究了SAT05f对小鼠急性肺损伤的干预作用。出乎意料的是,SAT05f只表现出轻度减轻肺病理损伤的作用,而作为对TLR7/9只在体外有微弱抑制作用的对照ODN(MS19)却明显地减轻了流感病毒引起急性肺组织病理损伤;抑制了小鼠的体重下降,减低了小鼠的死亡率。为了解释这种现象,我们对小鼠的肺组织中炎性细胞浸润、TNF-?和IL-10的表达水平进行了检测,结果显示:MS19能抑制小鼠肺组织中中性粒细胞浸润,且肺组织中TNF-?和IL-10的表达水平均降低。这些结果表明,MS19减轻肺损伤的作用与抑制肺组织炎症反应及TNF-?有关,是否其他机制也参与其中还有待进一步研究。
[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.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R392.1

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