Background

Intestinal barrier dysfunction in acute pancreatitis (AP) may progress to systemic inflammatory response syndrome (SIRS) and multi-organ failures by causing bacterial translocation. Larazotide acetate (LA) is a molecule that acts as a tight junction (TJ) regulator by blocking zonulin (Zo) receptors in the intestine.

Aims

In our study, we aimed to investigate the effects of LA on intestinal barrier dysfunction and bacterial translocation in the AP model in rats.

Methods

Thirty-two male Sprague-Dawley rats were divided into 4 groups; control, larazotide (LAR), AP, and AP + LAR. The AP model was created by administering 250 mg/100 g bm l-Arginine intraperitoneally 2 times with an hour interval. AP + LAR group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of l-Arginine. For intestinal permeability analysis, fluorescein isothiocyanate-dextran (FITC-Dextran) was applied to rats by gavage. The positivity of any of the liver, small intestine mesentery, and spleen cultures were defined as bacterial translocation. Histopathologically damage and zonulin immunoreactivity in the intestine were investigated.

Results

Compared to the control group, the intestinal damage scores, anti-Zo-1 immunoreactivity H-Score, serum FITC-Dextran levels and bacterial translocation frequency (100% versus 0%) in the AP group were significantly higher (all p < 0.01). Intestinal damage scores, anti-Zo-1 immunoreactivity H-score, serum FITC-Dextran levels, and bacterial translocation frequency (50% versus 100%) were significantly lower in the AP + LAR group compared to the AP group (all p < 0.01).

Conclusions

Our findings show that LA reduces the increased intestinal permeability and intestinal damage by its effect on Zo in the AP model in rats, and decreases the frequency of bacterial translocation as a result of these positive effects.

Graphical Abstract

中文翻译：

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醋酸拉扎肽对急性胰腺炎模型大鼠肠道通透性和细菌移位的改善作用

背景

急性胰腺炎（AP）的肠屏障功能障碍可能会导致细菌易位，进而发展为全身炎症反应综合征（SIRS）和多器官衰竭。醋酸拉拉佐肽 (LA) 是一种通过阻断肠道连蛋白 (Zo) 受体充当紧密连接 (TJ) 调节剂的分子。

目标

在我们的研究中，我们旨在研究 LA 对 AP 模型大鼠肠道屏障功能障碍和细菌易位的影响。

方法

32只雄性Sprague-Dawley大鼠分为4组；对照、拉扎肽 (LAR)、AP 和 AP + LAR。通过腹腔注射250mg/100g bml-精氨酸2次（间隔1小时）来创建AP模型。AP + LAR 组在第一次服用l-精氨酸之前口服 7 天预防性 0.01 mg/mL LA 。为了进行肠道通透性分析，将异硫氰酸荧光素-葡聚糖（FITC-葡聚糖）通过灌胃法施用于大鼠。肝脏、小肠系膜和脾脏培养物的任何阳性被定义为细菌易位。研究了肠道中的组织病理学损伤和连蛋白免疫反应性。

结果

与对照组相比，AP组的肠道损伤评分、抗Zo-1免疫反应性H-Score、血清FITC-葡聚糖水平和细菌移位频率（100% vs 0%）均显着升高（均p < 0.01  ） 。与 AP 组相比，AP + LAR 组的肠道损伤评分、抗 Zo-1 免疫反应性 H 评分、血清 FITC-右旋糖酐水平和细菌易位频率（50% 与 100%）显着较低（所有p  < 0.01） ）。

结论

我们的研究结果表明，LA 通过对大鼠 AP 模型中的 Zo 产生影响，减少了肠道通透性的增加和肠道损伤，并由于这些积极作用而降低了细菌易位的频率。

图形概要