Received:16 November 2020,
Published:30 May 2021
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Xiu YUAN, Shaojun LI, Chunxiao FU, et al. Effects of ghrelin on pyroptosis pathway and inflammatory factors in mice with septic lung injury[J]. Journal of Third Military Medical University, 2021, 43(10): 930-937.
Xiu YUAN, Shaojun LI, Chunxiao FU, et al. Effects of ghrelin on pyroptosis pathway and inflammatory factors in mice with septic lung injury[J]. Journal of Third Military Medical University, 2021, 43(10): 930-937. DOI: 10.16016/j.1000-5404.202011142.
Objective
2
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
2
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
2
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
2
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.
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