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Glycyrrhetinic acid improves inflammation and corneal injury induced by Pseudomonas aeruginosa by inhibiting GSDMD mediated atypical cell pyroptosis |
TANG Ying1, LI Pengfei2, YU Jinjin1 |
1. Department of Ophthalmology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi 214000, China; 2. Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong 226000, China |
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Abstract Objective To investigate how glycyrrhetinic acid improves inflammation and corneal injury induced by Pseudomonas aeruginosa by inhibiting Gasdermin-D (GSDMD) mediated atypical cell pyroptosis. Methods Prepare a rat model of Pseudomonas aeruginosa keratitis and randomly divide the rats into a control group, PA group, and GLY+PA group. Compare the keratitis index of each group; Enzyme linked immunosorbent assay (ELISA) was used to detect serum inflammatory factors; Hematoxylin eosin (HE) staining was used to detect pathological changes in corneal tissue; Immunofluorescence detection showed positive expression of caspase-11 and GSDMD in corneal tissue for cysteine; Protein blotting and qRT PCR were used to detect the expression of caspase-4, caspase-5, caspase-11, GSDMD protein, and mRNA in corneal tissue. Results The keratitis index and serum levels of interleukin-1β (IL-1 β) (78.54±8.03) and interleukin-18(IL-18) (26.31±2.74), inflammatory cell density, percentage of positive expression areas of caspase-11 and GSDMD, as well as the expression of caspase-4, caspase-5, caspase-11, GSDMD protein and mRNA in corneal tissue of rats in the PA group were significantly higher than those in the control group; Compared with the PA group, the GLY+PA group significantly reduced the keratitis index and serum levels of IL-1β (46.27±5.11) and IL-18(13.52±1.46), inflammatory cell density, percentage of positive expression areas of caspase-11 and GSDMD, as well as the expression of caspase-4, caspase-5, caspase-11, GSDMD protein and mRNA in corneal tissue. Conclusion Glycyrrhizic acid inhibits the corneal inflammatory response and tissue damage in rats with Pseudomonas aeruginosa keratitis, and its mechanism of action may be related to the inhibition of GSDMD-mediated activation of the atypical cellular pyroptosis pathway.
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Received: 27 March 2024
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