Paneth cell ablation increases the small intestinal injury during acute necrotizing pancreatitis in rats
Paneth cell ablation increases the small intestinal injury during acute necrotizing pancreatitis in rats
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DOI：
10.3892/mmr.2019.10274
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发表时间：
2019-07-01
影响因子：
3.4
通讯作者：
Wang, Xingpeng
中科院分区：
文献类型：
--
作者：
Liu, Liyan;Guo, Yuecheng;Wang, Xingpeng
本研究旨在探讨Paneth细胞在急性坏死性胰腺炎（ANP）期间小肠损伤中的作用，通过注射双硫腙（一种锌金属螯合剂，具有选择性消融Paneth细胞的能力）建立大鼠模型。将sd - dawley大鼠随机分为假手术组、ANP组（3.5%牛磺胆酸钠溶液，1 ml/kg体重）、双硫腙组（100 mg/kg体重）和ANP +双硫腙组（注射双硫腙后6 h给予牛磺胆酸钠溶液）。根据模型诱导至样品采集的时间，将各组进一步分为5个亚组（6、12、24、36、48 h）。本研究结果提示ANP组Paneth细胞数量呈时间依赖性逐渐减少。在ANP +双硫松组，大部分Paneth细胞在6 h时被吞噬，但在24-48 h后有一部分Paneth细胞恢复。与ANP组相比，双硫松和ANP联合组胰腺和回肠远端组织病理损伤更严重，Schmidt和Chiu's评分分别更高。此外，在回肠中检测到肿瘤坏死因子- α (tnf - α)、白细胞介素(IL)-1 β和IL- 17a的表达水平升高，导致肠通透性增加，通过肠紧密连接蛋白occludin的表达水平降低和血浆中二胺氧化酶和d -乳酸的高水平来评估。肠道通透性的增加导致细菌转移到血液中，引发全身炎症，通过提高血浆中tnf - α、IL-1 β和IL-17A的水平来评估，降低了大鼠的存活率，ANP +双硫腙组和ANP组的存活率分别为66.7%和83.3%。通过结合免疫球蛋白蛋白和激活转录因子6的高表达水平来评估，肠道内质网应激的增加可能是ANP期间Paneth细胞损失和肠屏障损伤的一种机制。综上所述，本研究提示Paneth细胞的缺失可能是肠损伤的一个重要因素，促进ANP的进展。
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-alpha (TNF-alpha), interleukin (IL)-1 beta 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-alpha, IL-1 beta 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.