Abstract
Hemorrhagic shock and resuscitation (HSR) can induce severe intestinal damages, thereby leading to sepsis and long-term complications including dysbacteriosis and pulmonary injury. The NOD-like receptor protein 3 (NLRP3) inflammasome facilitates inflammation-associated cell recruitment in the gastrointestinal tract, and participates in many inflammatory bowel diseases. Previous studies have shown that exogenous carbon monoxide (CO) exerts neuroprotective effects against pyroptosis after HSR. We aimed to investigate whether carbon monoxide-releasing molecules-3 (CORM-3), an exogenous CO compound, could attenuate HSR-induced intestinal injury and the potential underlying mechanism.Rats were subjected to a HSR model by bleeding and re-infusion. Following resuscitation, 4 mg/kg of CORM-3 was administered intravenously into femoral vein. At 24 h and 7 d after HSR modeling, the pathological changes in intestinal tissues were evaluated by H&E staining. The intestinal pyroptosis, glial fibrillary acidic protein (GFAP)-positive glial pyroptosis, DAO (diamine oxidase) content, intestine tight junction proteins including zonula occludens-1 (ZO-1) and claudin-1 were further detected by immunofluorescence, western blot and chemical assays at 7 d after HSR. CORM-3 administration led to significantly mitigated HSR-induced intestinal injury, aggravation of intestinal pyroptosis indicated by cleaved caspase-1, IL-1β and IL-18, upregulation of GFAP-positive glial pyroptosis, decreased intensity of ZO-1 and claudin-1 in the jejunum, and increased of DAO in the serum. Nigericin, an agonist of NLRP3, significantly reversed the protective effects of CORM-3. CORM-3 alleviates the intestinal barrier dysfunction in a rodent model of HSR, and the potential mechanism may be associated with inhibition of NLRP3-associated pyroptosis. CORM-3 administration could be a promising therapeutic strategy for intestinal injury after hemorrhagic shock.
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All data generated and analyzed during the present study are included in this published article.
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Funding
This study was supported by the National Natural Science foundation of China (No. 81701296, 82171455), Natural Science foundation of Hebei Province (No. H2021110004), and Wu Jieping Medical Foundation (320.6750.17533).
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Design of the study: Li-Min Zhang, Yue Xin, Dong-Xue Zhang. Editing the manuscript: Li-Min Zhang, Yue Xin, Dong-Xue Zhang. Statistical analysis: Li-Min Zhang, Yue Xin, Wei-Chao Zheng, Jin-Shu Hu, Rong-Xin Song. Experiment and data collection: Yue Xin, Jie-Xia Wang, Wei-Chao Zheng, Zhi-You Wu. All authors read and approved the final manuscript.
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Zhang, LM., Xin, Y., Song, RX. et al. CORM-3 alleviates the intestinal injury in a rodent model of hemorrhage shock and resuscitation: roles of GFAP-positive glia. J Mol Histol 54, 271–282 (2023). https://doi.org/10.1007/s10735-023-10133-w
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DOI: https://doi.org/10.1007/s10735-023-10133-w