Background: Hydrogen sulfide (H2S), a common air pollutant and toxic gas, which is harmful to organisms and the environment. Exposure to high concentrations of H2S can lead to necrosis and inflammation. However, the potential mechanism of H2S-induced hepatotoxicity and the role of microRNA (miRNA) in this process are still poorly understood. In this experiment, 80 one-day-old chickens were used as model organisms to evaluate the effects of H2S and Lipopolysaccharide (LPS) on poultry liver. Four groups (Control group, LPS group, H2S group, H2S-LPS group) were established. Liver tissue was collected after 42 days of age. Ultrastructural observation, pathological tissue observation, immunofluorescence analysis, real-time quantitative PCR analysis and Western blot analysis were used to detect.
Results: The results showed that obvious pyroptosis was observed in ultrastructure. Histopathological observation showed obvious necrosis and inflammatory injury in broiler liver tissue. By detecting the expression of miR-216a in the four groups, we verified that miR-216a can target chicken PKCα. Molecular level studies showed that H2S exposure could inhibit the expression of miR-216a, promote the up-regulation of PKCα, activate the NF-κB/TNFα signaling pathway, induce cell necrosis (necrosis marker factors RIP1, RIP3, caspase8, MLKL, NLRP3) and pyroptosis-related gene expression (ASC, caspase1, GSDMD), and eventually lead to inflammatory injury of chicken liver (IL-1β, IL-6, IL-18, iNOS).
Conclusions: We concluded that H2S induced the imbalance of the NF-κB/TNFα signaling pathway through miR-216a/PKCα axis, leading to chicken liver necrosis and cell pyroptosis, and further causing inflammatory injury. Notably, we also found that H2S aggravated LPS-induced liver inflammation. This study can provide reference to the pathological mechanism of animal damage and poultry poisoning caused by H2S pollution in the atmospheric environment.