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Mol Med Rep. 2019 Jul;20(1):473-484. doi: 10.3892/mmr.2019.10274. Epub 2019 May 22.

Paneth cell ablation increases the small intestinal injury during acute necrotizing pancreatitis in rats.

Author information

1
International Medical Care Center, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China.
2
Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China.
3
Department of Gastroenterology, Shanghai Fourth People's Hospital, Shanghai 200080, P.R. China.

Abstract

The present work aimed to investigate the role of Paneth cells in small intestinal injury during acute necrotizing pancreatitis (ANP) using rat models established by injection of dithizone, a metal chelator of zinc with the ability to selectively ablate Paneth cells. Sprague‑Dawley rats were randomly divided into four groups: Sham‑operated group, ANP group (3.5% sodium taurocholate solution, 1 ml/kg body weight), dithizone group (100 mg/kg of body weight) and ANP + dithizone group (sodium taurocholate solution was administered 6 h after dithizone injection). Each group was further divided into five subgroups (6, 12, 24, 36 and 48 h) based on the time period between induction of the model and sample collection. The present results suggested the number of Paneth cells was gradually decreased in the ANP group in a time‑dependent manner. Most of the Paneth cells were ablated in the ANP + dithizone group at 6 h, but a subset of Paneth cells recovered after 24‑48 h. Compared with the ANP group, combination of dithizone and ANP significantly induced more severe histopathological injuries in the pancreas and distal ileum, with higher Schmidt and Chiu's scores, respectively. Additionally, increased expression levels of tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β and IL‑17A were detected in the ileum, causing an increase in intestinal permeability, as assessed by a decrease in the expression level of the intestinal tight junction protein occludin and high plasma levels of diamine oxidase and D‑lactate. The increase in intestinal permeability led to the translocation of bacteria to the bloodstream, triggering systemic inflammation, as assessed by the increased plasma levels of TNF‑α, IL‑1β and IL‑17A, reducing the survival rates of rats, which was 66.7% and 83.3% in the ANP + dithizone and the ANP group, respectively. The increase in intestinal endoplasmic reticulum stress, as assessed by high expression levels of binding‑immunoglobulin protein and activating transcription factor 6, may be one mechanism associated with Paneth cells loss and intestinal barrier impairment during ANP. Collectively, the present study suggested that the absence of Paneth cells may be an important factor involved in intestinal injury, promoting the progression of ANP.

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