Curcumin improves necrotising microscopic colitis and cell pyroptosis by activating SIRT1/NRF2 and inhibiting the TLR4 signalling pathway in newborn rats

Abstract

This study aimed to explore comprehensively the biological function of curcumin, and its underlying mechanism, in protecting from necrotising microscopic colitis in newborn rats. A total of 20 normal healthy rats were selected, and a necrotising enterocolitis (NEC) model was established. After hypoxia and hypothermia stimulation, these rats were treated with different doses of curcumin (control group, NEC model group, NEC+20 mg/kg curcumin and NEC+50 mg/kg curcumin). Inflammation was identified using hematoxylin and eosin staining, and inflammatory factors were detected via ELISA. The mRNA and protein levels of SIRT1, NRF2, TLR4, NLRP3 and caspase-1 were determined by quantitative RT-PCR and Western blotting, respectively. Curcumin improved the inflammatory condition of NEC and inhibited the expression of inflammatory factors in NEC newborn rat intestinal tissue. Furthermore, the SIRT1/NRF2 pathway was inhibited in the intestinal tissue of NEC newborn rats, whereas curcumin treatment induced the activation of the SIRT1/NRF2 pathway and inhibited TLR4 expression in these animals. In addition, curcumin could also inhibit the expression of inflammatory factors and alleviate the LPS/ATP-induced focal death pathway in intestinal epithelial cells through the SIRT1 pathway. Curcumin can improve necrotising microscopic colitis and cell pyroptosis by attenuating NEC-induced inhibition of SIRT1/NRF2 and inhibiting the TLR4 signalling pathway in newborn rats.