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首页> 中文期刊> 《中国病理生理杂志》 >山柰酚通过下调 NF-κB 信号通路减轻猪源甲型H9 N2流感病毒所致小鼠急性肺损伤

山柰酚通过下调 NF-κB 信号通路减轻猪源甲型H9 N2流感病毒所致小鼠急性肺损伤

         
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[ ABSTRACT] AIM:To investigate whether kaempferol protects against acute lung injury induced by swine -origin influenza A H9N2 virus via down-regulation of NF-κB signaling pathway .METHODS:BALB/c mice were used to estab-lish the animal model of acute lung injury by nasal inoculation of swine-origin influenza A H9N2 virus.After the interven-tion with kaempferol , the pulmonary edema was evaluated by determining the lung wet weight /dry weight ( W/D) ratio, the pathological changes of the lung tissues were observed , the concentrations of TNF-α, IL-1βand IL-6 in the bronchoalveolar lavage fluid (BALF) were measured, and superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity and MDA content in the homogenate of the lung tissues were detected .NF-κB P65 levels were determined by Western blot , and the NF-κB P65 and NF-κB P50 nuclear translocation in the nuclear extracts from mouse lung tissue homogenate was detec-ted by ELISA .RESULTS:Treatment with kaempferol decreased the morality of infected mice , and significantly prolonged the survival time of the infected mice .Kaempferol also relieved the pathological changes of the lung tissues , the lung W/D ratio and the lung index in swine-origin influenza A H9N2 virus-infected mice.Treatment with kaempferol significantly de-creased the infiltration of inflammatory cells including macrophages , lymphocytes and neutrophils in the BALF .The levels of TNF-α, IL-6, IL-1βand MDA and the activity of MPO were also decreased .Treatment with kaempferol also significantly increased the SOD activity .NF-κB P65 levels were decreased , and the NF-κB P65 and NF-κB P50 nuclear translocation in the nuclear extracts from the mouse lung tissue homogenate were also decreased by treatment with kaempferol .CONCLU-SION:The protective effect of kaempferol on the mice with acute lung injury induced by swine -origin influenza A H9N2 vi-rus is related to suppression of the oxidative stress and inflammatory responses by down-regulation of NF-κB signaling path-way.%目的：探讨山柰酚是否通过下调转录因子NF-κB信号通路的表达而保护感染猪源甲型H9N2流感病毒引起急性肺损伤的小鼠。方法：猪源甲型H9N2流感病毒感染BALB／c小鼠建立急性肺损伤模型，山柰酚干预后检测肺湿重与干重比，观察肺组织的病理学变化，检测支气管肺泡灌洗液内炎性细胞数量以及肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和白细胞介素1β（IL-1β）含量，同时检测肺组织匀浆中超氧化物歧化酶（SOD）和髓过氧化物酶（ MPO）活性以及丙二醛（ MDA）含量，Western blot检测小鼠肺内NF-κB P65的表达，ELISA检测小鼠肺组织匀浆细胞核提取物中NF-κB P65和NF-κB P50的核转位。结果：山柰酚能降低小鼠死亡率，改善肺组织的病理学变化和肺水肿程度，并能降低肺内巨噬细胞、淋巴细胞和中性粒细胞等炎性细胞的数量，同时降低TNF-α、IL-6、IL-1β和MDA的含量，抑制MPO的活性并升高SOD的活性。另外，山柰酚可以下调NF-κB P65的表达，增加细胞核提取物中NF-κB P65和NF-κB P50的核转位。结论：山柰酚通过下调NF-κB信号通路的表达从而降低猪源甲型H9 N2流感病毒所致急性肺损伤小鼠的炎症程度和氧化应激损伤，最终减轻流感病毒所致的急性肺损伤。

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