| Summary: | Objective To investigate the regulative role of chromogranin A derived polypeptide CGA47-66 (chromofungin, CHR) on autophagy flux and determine its effect on inflammatory injury in the lung tissue of septic mice. Methods C57BL/6 mice were inflicted by intraperitoneal administration of 10 mg/kg lipopolysaccharide to establish a mouse septic model of acute lung injury. To determine the effect of CHR on autophagy, the mice were pretreated with CHR and autophagy inducer rapamycin (Rapa) respectively in 30 min before LPS administration. The pathological changes of lung tissue in mice were observed, contents of inflammatory factors in alveolar lavage were measured, expression of autophagy-related markers LC3, P62 and Agt7 in lung tissues were determined by Western blotting and immunofluorescence assay, and formation of autophagosomes was observed by transmission electron microscopy. Results Compare with the LPS group, CHR pretreatment significantly attenuated LPS-induced lung pathological damages, and inhibited the expression of pro-inflammatory factors and enhanced the expression of anti-inflammatory factors in bronchoalveolar lavage fluid of mice (P < 0.05). The results of Western blotting and immunofluorescence assay showed that the expression of autophagy marker proteins were up-regulated and the expression of autophagy substrate protein was down-regulated in the lung tissues after CHR pretreatmnet (P < 0.05). Transmission electron microscopy displayed autophagosomes and autophagosolysosomes were formed in the CHR pretreatment group. The changes of autophagy flux, inflammatory mediators and lung pathology were consistent with the results in the Rapa group. Conclusion CHR may attenuate the inflammatory response by regulating the increase of autophagy flux in lung tissue after LPS stimulation and play a protective role in the lung of septic mice.
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