Protective effects of salvianolic acid B on intestinal ischemia/reperfusion injury in rats by regulating the AhR/IL-22/STAT6 axis

Abstract

Purpose

Intestinal ischemia/reperfusion (I/R) injury (IIRI) is associated with high morbidity and mortality. Salvianolic acid B (Sal-B) could exert neuroprotective effects on reperfusion injury after cerebral vascular occlusion, but its effect on IIRI remains unclear. This study set out to investigate the protective effects of Sal-B on IIRI in rats.

Methods

The rat IIRI model was established by occluding the superior mesenteric artery and reperfusion, and they were pretreated with Sal-B and aryl hydrocarbon receptor (AhR) antagonist CH-223191 before surgery. Pathological changes in rat ileum, IIRI degree, and intestinal cell apoptosis were evaluated through hematoxylin-eosin staining, Chiu’s score scale, and TUNEL staining, together with the determination of caspase-3, AhR protein level in the nucleus, and STAT6 phosphorylation by Western blotting. The levels of inflammatory cytokines (IL-1β/IL-6/TNF-α) and IL-22 were determined by ELISA and RT-qPCR. The contents of superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in intestinal tissues were determined by spectrophotometry.

Results

Sal-B alleviated IIRI in rats, evidenced by slight villi shedding and villi edema, reduced Chiu’s score, and diminished the number of TUNEL-positive cells and caspase-3 expression. SAL-B alleviated inflammation and oxidative stress (OS) responses induced by IIRI. Sal-B promoted IL-22 secretion by activating AhR in intestinal tissue after IIRI. Inhibition of AhR activation partially reversed the protective effect of Sal-B on IIRI. Sal-B promoted STAT6 phosphorylation by activating the AhR/IL-22 axis.

Conclusion

Sal-B plays a protective role against IIRI in rats by activating the AhR/IL-22/STAT6 axis, which may be achieved by reducing the intestinal inflammatory response and OS responses.

Keywords:

• Salvianolic acid B
• Intestinal ischemia/reperfusion injury
• Aryl hydrocarbon receptor
• Interleukin-22
• STAT6
• Inflammation

Disclosure statement

The authors have no conflicts of interest to declare.

Data availability statement

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.