绿原酸通过抑制NF-κB/NLRP3通路介导的细胞焦亡改善慢性应激致大鼠肠道损伤

doi:10.11843/j.issn.0366-6964.2025.12.050

Abstract

Abstract: The aim of this study was to investigate the protective effect of chlorogenic acid (CGA) against chronic stress-induced intestinal injury in rats and its regulatory role in the nuclear factor-kappa B/NOD-like receptor protein 3 (NF-κB/NLRP3) pathway-mediated pyroptosis, in order to provide new strategies for preventing stress-related intestinal diseases in livestock. Thirty-two Sprague-Dawley (SD) rats with an initial body weight of 200±20 g were randomly divided into four groups: control group (CON group), chlorogenic acid group (CGA group), chronic restraint stress group (CRS group), and chlorogenic acid intervention group (CRS+CGA group). The CON group received no intervention. The with CGA group was administered CGA via gavage at a dose of 100 mg·kg^-1. The CRS group was subjected to 6 h of daily restraint for 21 d consecutively. The CRS+CGA group was gavaged with an equivalent dose of CGA and followed by the same restraint procedures as the CRS group. Open-field test was conducted on day 22 to evaluate the model establishment. Rats were euthanized on day 23 for blood and ileum collection. Serum corticosterone (CORT) levels were measured, ileum histopathology was observed by hematoxylin-eosin (HE) staining, inflammatory cytokine levels in the ileum were detected by enzyme-linked immunosorbent assay (ELISA), tight junction (TJs) proteins and gene expression were analyzed by immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR), and pyroptosis-related proteins were assayed by Western blot. The results showed that the chronic stress model was successfully established. CGA intervention significantly promoted average daily body weight gain of rats under chronic stress (P<0.01), alleviated ileum structural damage, reduced inflammatory cytokine levels (P<0.01), upregulated TJs-related proteins and gene Occludin, Claudin3, Zonula occludens-1 (ZO-1) expression (P<0.01), and inhibited pyroptosis-related proteins nuclear factor-kappa B p65 (NF-κB p65), NLRP3, cysteinyl aspartate specific proteinase-1 p20 (Caspase-1 p20), and N-gasdermin D (N-GSDMD) expression (P<0.01). Collectively, CGA alleviates chronic stress-induced ileum injury in rats, possibly by inhibiting the NF-κB/NLRP3 pathway, attenuating pyroptosis, reducing inflammatory cytokine levels, and thereby enhancing intestinal barrier function.

Key words: chlorogenic acid, chronic stress, ileum injury, intestinal barrier function, pyroptosis

CLC Number:

S856.4

ZHANG Hexin, QU Youyang, CHEN Ruoxuan, HE Huan, TANG Qichao, YIN Baishuang, WANG Ben, FENG Xiujing. Chlorogenic Acid Ameliorates Chronic Stress-Induced Intestinal Injury in Rats by Inhibiting NF-κB/NLRP3 Pathway-Mediated Pyroptosis[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(12): 6502-6512.

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Chlorogenic Acid Ameliorates Chronic Stress-Induced Intestinal Injury in Rats by Inhibiting NF-κB/NLRP3 Pathway-Mediated Pyroptosis

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