Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (1): 14-21.doi: 10.6040/j.issn.1671-7554.0.2020.1230

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Effects of naringenin on acute lung injury induced by sepsis via regulating the activation of NLRP3 inflammasome in macrophages

JIANG Yong1, SONG Jiangang2, ZHU Daxia1, LIU Lijian1   

  1. 1. Emergency Department;
    2. Department of Hand and Foot Surgery, Nanhua Hospital Affiliated to Nanhua University, Hengyang 421002, Hunan, China
  • Published:2021-01-09

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Abstract: Objective To investigate the effects of naringenin(NAR)on sepsis-induced acute lung injury by regulating the activation of NOD-like receptor protein 3(NLRP3)inflammasomes in macrophages. Methods A total of 60 male SD rats were divided into sham operation group, model group, low-dose NAR group(L-NAR, 25 mg/kg)and high-dose NAR group(H-NAR, 75 mg/kg)by random digital table method, with 15 rats in each group. The rat models of sepsis were prepared by cecal ligation and puncture(CLP), and different concentrations of NAR were intraperitoneally injected at 6, 12, and 18 h after the operation. At 24 h after CLP, blood samples were taken with internal carotid artery cannula to measure oxygenation index(OI). The bronchoalveolar lavage fluid(BALF)was collected and macrophages were isolated. The mRNA and protein expressions of NLRP3, apoptosis associated speck like protein containing a CARD(ASC)and caspase-1 in the macrophages were detected with RT-PCR and Western blotting, respectively. The wet/dry ratio(W/D)of lung tissues was determined, and the histopathological changes were observed with HE staining. The level of macrophages in lung tissues was detected with immunofluorescence staining, and the levels of interleukin-1β(IL-1β)and interleukin-1β(IL-18)in lung tissues and BALF were determined with ELISA. Results (1) Compared with the sham group, the model group had severer lung tissue injury, elevated lung histopathological score, W/D and macrophage level(P<0.05), decreased OI(P<0.05), increased expressions of IL-1β and IL-18 in lung tissues and BALF, as well as increased NLRP3 mRNA(1.027±0.064 vs 5.567±0.208)and protein(0.043±0.001 vs 1.242±0.065), ASC mRNA(0.993±0.035 vs 5.000±0.200)and protein(0.018±0.001 vs 0.433±0.060), and caspase-1 mRNA(0.973±0.038 vs 7.667±0.351)and protein(0.101±0.001 vs 0.959±0.078)in macrophages(P<0.05). (2) Compared with the model group, the H-NAR group showed improved lung tissue injury, decreased lung histopathological score, W/D and macrophage level(P<0.05), increased OI(P<0.05), decreased expressions of IL-1β and IL-18 in lung tissues and BALF, as well as decreased NLRP3 mRNA(5.567±0.208 vs 3.367±0.473)and protein(1.242±0.065 vs 0.172±0.023), ASC mRNA(5.000±0.200 vs 3.433±0.404)and protein(0.433±0.060 vs 0.121±0.010)and caspase-1 mRNA(7.667±0.351 vs 4.000±0.200)and protein(0.959±0.078 vs 1.020±0.088)in macrophages(P<0.05). (3) There were no significant differences in the indicators between the L-NAR group and model group(P>0.05). Conclusion Naringenin can alleviate acute lung injury in sepsis rats, and the mechanism may be related to the inhibition of the activation of NLRP3 inflammasomes in alveolar macrophages.

Key words: Naringenin, Sepsis, Acute lung injury, Macrophages, NOD-like receptor protein 3

CLC Number: 

  • R574
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