Abstract
Background Inflammatory responses induced by intestinal ischemia-reperfusion (IIR) lead to serious systemic organ dysfunction and pose a challenge for current treatment. This study aimed at investigating the effects of resveratrol on IIR-induced intestinal injury and its influence on mast cells (MCs) in rats. Methods Rats subjected to intestinal ischemia for 60 min and 4 h of IIR were investigated. Animals were randomly divided into five groups (n = 8 per group): sham, IIR, resveratrol (RESV, 15 mg/kg/day for 5 days before operation) + IIR, cromolyn sodium (CS, MC membrane stabilizer) + IIR, and RESV + compound 48/80 (CP, MC agonist) + IIR. Results Intestinal injury and increased proinflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-18 were observed in the IIR group. Intestinal MC-related tryptase and β-hexosaminidase levels were also increased after rats were subjected to IIR accompanied by activation of NLRP3 inflammasomes. Interestingly, pretreatment with resveratrol significantly suppressed the activities of proinflammatory cytokines and attenuated intestinal injury. Resveratrol also reduced MC and NLRP3 inflammasome activation, which was consistent with the effects of cromolyn sodium. However, the protective effects of resveratrol were reversed by the MC agonist compound 48/80. Conclusions In summary, these findings reveal that resveratrol suppressed IIR injury by stabilizing MCs, preventing them from degranulation, accompanied with intestinal mucosa NLRP3 inflammasome inhibition and intestinal epithelial cell apoptosis reduction.
Highlights
Inflammatory responses induced by intestinal ischemia-reperfusion (IIR) lead to serious systemic organ dysfunction and pose a challenge for current treatment
In RESV + IIR or Cromolyn sodium (CS) + IIR pretreatment groups, the villus arrangement was relatively regular, with no evidence of the loss of intestinal villi, and only small gaps formed at the top of the intestinal villi and few inflammatory cells were found in the intestine (Figure 1(a))
Both resveratrol and cromolyn sodium pretreatment significantly improved the Chiu’s score and reduced the serum levels of the proinflammatory cytokines tumor necrosis factor (TNF)-α, IL-1β, and IL-18 compared to the IIR group (P < 0 05) (Figures 1(b)–1(e))
Summary
Inflammatory responses induced by intestinal ischemia-reperfusion (IIR) lead to serious systemic organ dysfunction and pose a challenge for current treatment. This study aimed at investigating the effects of resveratrol on IIR-induced intestinal injury and its influence on mast cells (MCs) in rats. Intestinal MC-related tryptase and β-hexosaminidase levels were increased after rats were subjected to IIR accompanied by activation of NLRP3 inflammasomes. Resveratrol reduced MC and NLRP3 inflammasome activation, which was consistent with the effects of cromolyn sodium. These findings reveal that resveratrol suppressed IIR injury by stabilizing MCs, preventing them from degranulation, accompanied with intestinal mucosa NLRP3 inflammasome inhibition and intestinal epithelial cell apoptosis reduction. The natural barrier function of the intestine breaks down following IIR, which results in bacterial translocation, endotoxemia, and uncontrolled release of inflammatory mediators and cytokines.
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