Berberine protects against lung injury induced by liver transplantation through upregulating PPARγ and suppressing NF-κB-mediated pyroptosis pathway.

PURPOSE: We builted a orthotopic autologous liver transplantation (OALT) model in rats to evaluate the possible mechanisms of berberine against lung injury.

METHODS

Forty clean grade Sprague-Dawley rats (male, healthy, 250-280 g) were divided into five groups (n = 8): sham-operated group (group S), orthotopic autologous liver transplantation group (group T), berberine group (group B), peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 group (group G), and berberine + GW9662 group (group B+G). In group S, the relevant tissues around the liver were dissociated only. Orthotopic autologous liver transplantation was used in other groups, berberine 200 mg/kg/day was given one week before surgery in group B and group B+G. GW9662 1 mg/kg was intraperitoneally injected in group G and group B+G 4 hours before surgery. Blood samples were obtained for detecting PaO2 and the concentration of serum clam cell protein (CC16), surfactant protein-D (SP-D), interleukin (IL)-1β and IL-18. The immunohistochemical method detects the expression of PPARγ and nuclear factor-kappa B (NF-κB) in lung tissues. The expression of PPARγ, NF-κBand pyroptosis-related proteins were analysed by western blotting.

RESULTS

Rats exhibited increased histological lung injury following OALT. Liver transplantation caused upregulated CC16, SP-D, IL-18 and IL-1β levels, reduced PaO2 and the PPARγ expression, upregulated the NF-κB and pyroptosis-related protein expressions. BBR pretreatment greatly alleviates these lung damages induced by OALT. However, administration of GW9662 partially reversed the beneficial effects of BBR on lung injury.

CONCLUSION

Berberine may play protective capacities against lung injury by upregulating PPARγ to downregulate the NF-κB-mediated pyroptosis pathway.