Di-san junyi daxue xuebao (May 2021)

Effects of ghrelin on pyroptosis pathway and inflammatory factors in mice with septic lung injury

  • YUAN Xiu,
  • YUAN Xiu,
  • LI Shaojun,
  • FU Chunxiao,
  • FU Chunxiao,
  • ZHOU Liang,
  • ZOU Zhiping,
  • TAN Liping

DOI
https://doi.org/10.16016/j.1000-5404.202011142
Journal volume & issue
Vol. 43, no. 10
pp. 930 – 937

Abstract

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Objective To analyze the effects of ghrelin on the pyroptosis pathway and the expression of inflammatory factors in septic lung injury, and explore its protective mechanism. Methods A total of 180 healthy male C57 BL/6 mice were divided into sham operation group (sham, n=24), cecal ligation and puncture group (CLP, n=78) and ghrelin group (n=78). The ghrelin group was intraperitoneally given ghrelin 12 nmol/kg at 3 h and 20 h after CLP surgery, while the other groups were given the same amount of normal saline. The 120-hour survival rate of each group was observed, and the bronchoalveolar lavage fluid (BALF) and lung tissues of mice in 6, 12 and 24 h after CLP group, ghrelin group and in 24 h for sham groups were collected respectively, and the total protein concentration and total cell number in BALF were detected. The expression of ghrelin as well as inflammatory cytokines such as IL-10, IL-6, TNF-α, IL-1β and IL-18 was tested by ELISA. Moreover, the expression of gasdermin D (GSDMD) was determined by immunofluorescence staining, and the levels of pyroptosis signal pathway proteins including NOD-like receptor protein (NLRP3), ASC, Caspase-1 and GSDMD were detected by qPCR and Western blotting. Results As compared with sham group, the mortality, pathological changes of lung tissue and levels of inflammatory factors (IL-10, IL-6, TNF-α, IL-1β and IL-18) in CLP group were significantly increased (P < 0.05); the level of ghrelin in the lung tissue was dropped, while those of NLRP3, ASC, Caspase-1 and GSDMD rose in the CLP group (P < 0.05). After administration of exogenous ghrelin, the death rate of septic lung injury mice was declined, the pathological damage of lung tissue was alleviated, and the expression levels of inflammatory cytokines and NLRP3, ASC, Caspase-1 and GSDMD were all decreased (P < 0.05). Conclusion Ghrelin improves the survival rate of septic lung injury mice and reduces the pathological changes of lung tissue, which may play a protective role by inhibiting the pathway of pyroptosis and alleviating inflammation.

Keywords