Senegenin Alleviates Acute Lung Injury Induced by Sepsis via Promoting the Expression of Clara Cell Protein 16

Background: Sepsis usually causes acute lung injury (ALI). Our prior findings show that Clara cell protein 16 (CC16) protects the lung from injury caused by lipopolysaccharide (LPS), meanwhile senegenin significantly reduces the mortality of sepsis rats. But the underlying mechanisms are not known yet. In this study, we investigated whether senegenin can alleviate the acute lung injury (ALI) induced by sepsis via modulating the expression of CC16. Methods: The ALI in mice was induced by Sepsis, which was prepared by cecal ligation and puncture (CLP). Mice were randomized into four groups: (1) Sham, (2) CLP, (3) CLP + Veh (CLP+ Vehicle), and (4) CLP + Senegenin (CLP+SEN) groups. The mice in CLP+SEN group were injected with senegenin before surgery and 4h post-surgery, followed by one injection per day for four consecutive days. Those in Sham and CLP groups were injected with equal volume of normal saline, while those in CLP+ Veh group received the relevant solvent. The mice’s lung histopathology, lung wet/dry weight ratio, and survival rate were assessed. The mRNA levels of IL-1β, IL-6, TNF-α, CC16 and secreted phospholipase A2 (sPLA2) in lungs were detected. The protein levels of CC16 and sPLA2 were quantified by immunofluorescence staining. Results: Hematoxylin-eosin (HE) staining of lung tissues showed that the lung injury in senegenin treated group was much less than those in CLP group and CLP+ Veh group ( p <0.05). The lung wet/dry weight ratio in senegenin treated group was lower than CLP group and CLP+ Veh group ( p <0.05). The survival rate of mice in senegenin group was higher than those in CLP group and CLP+ Veh group ( p <0.05). The mRNA levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in senegenin group were significantly lower than CLP group and CLP+ Veh group ( p <0.05). Senegenin treatment increased the mRNA and protein levels of CC16, while decreased the mRNA and protein levels of sPLA2 in sepsis mice’s lungs. Conclusion: Senegenin alleviate the acute lung injury induced by sepsis and reduces the mortality of sepsis mice. The underlying mechanisms may be associated with its modulation on the CC16/sPLA2 pathway.