Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition.
OBJECTIVE
To investigate the effects of quercetin on intestinal barrier disruption and inflammation in acute necrotizing pancreatitis (ANP) in rats, and its possible mechanism.


METHODS
ANP was established by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, and quercetin (50 mg/kg × 3) was administered by intraperitoneal injection prior to and after ANP induction. Pancreatitis was assessed by pancreatic histopathology, plasma amylase, pancreatic myeloperoxidase (MPO) activity, IL-1β, TNFα and IL-6 levels. Injury of the distal ileum was assessed by histological evaluation. The ultrastructural changes of ileal epithelial cells were examined by transmission electron microscope (TEM). Intestinal barrier function was estimated by plasma diamine oxidase (DAO), d-lactate, endotoxin; and intestinal tight junction proteins including zonula occludens-1 (ZO-1), claudin 1, occludin; and bacterial translocation. Intestinal inflammation was determined by IL-1β, TNFα and IL-17 A expression. TLR4, MyD88, pp38 MAPK, and endoplasmic reticulum stress (ERS)-related molecules (Bip, p-IRE1α, sXBP1, p-eIF2α, ATF6) were measured by immunohistochemistry and WB.


RESULTS
Quercetin intervention attenuated pancreatic and ileal pathological damages in ANP (P < 0.05), ameliorated intestinal barrier disruption and inflammation (P < 0.05). Meantime, QE significantly suppressed intestinal TLR4/MyD88/p38 MAPK pathway and ERS activation.


CONCLUSIONS
Quercetin plays a protective role against intestinal barrier disruption and inflammation in ANP, probably partly by inhibiting TLR4/MyD88/p38 MAPK and ERS activation.
['Junyuan|Zheng|Z|', 'Hui|Xu|X|', 'Chunlan|Huang|H|', 'Junjie|Fan|F|', 'Qixiang|Mei|M|', 'Yingying|Lu|L|', 'Lihong|Lou|L|', 'Xingpeng|Wang|W|', 'Yue|Zeng|Z|']
D059865:Endoplasmic Reticulum Stress D005786:Gene Expression Regulation D006801:Humans D007249:Inflammation D007422:Intestines D053594:Myeloid Differentiation Factor 88 D019283:Pancreatitis, Acute Necrotizing D011794:Quercetin D013656:Taurocholic Acid D051197:Toll-Like Receptor 4 D048051:p38 Mitogen-Activated Protein Kinases
Quercetin Acute necrotizing pancreatitis Ileum Endoplasmic reticulum stress TLR4/MyD88/p38 MAPK pathway