山柰酚通过下调NF-κB信号通路减轻猪源甲型H9N2流感病毒所致小鼠急性肺损伤

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H9N2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。

Kaempferol attenuates acute lung injury in mice induced by swine-origin influenza A H9N2 virus via down-regulation of NF-κB signaling pathway

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 establish the animal model of acute lung injury by nasal inoculation of swine-origin influenza A H9N2 virus. After the intervention 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-1β and 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 detected 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 decreased the infiltration of inflammatory cells including macrophages, lymphocytes and neutrophils in the BALF. The levels of TNF-α, IL-6, IL-1β and 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.CONCLUSION: The protective effect of kaempferol on the mice with acute lung injury induced by swine-origin influenza A H9N2 virus is related to suppression of the oxidative stress and inflammatory responses by down-regulation of NF-κB signaling pathway.