Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis |
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Authors: | Like Qian Xi Yin Jiahao Ji Zhengli Chen He Fang Hu Li Feng Zhu Fei Chang |
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Institution: | 1.Department of Burn and Plastic Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China; 2.Burn Institute of PLA, Department of Burn Surgery, The First Affiliated Hospital. Naval Medical University, Shanghai, China |
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Abstract: | BackgroundThe role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear.MethodsSixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups.ResultsThe wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups.ConclusionTNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration. |
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Keywords: | Tumor necrosis factor-α siRNA nanoparticle lung sepsis alveolar epithelial cells |
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