Severe acute pancreatitis (SAP), which is characterized by acute onset and high mortality, is complicated with systemic inflammatory response syndrome. This study investigated the molecular mechanism underlying SAP-induced intestinal mucosal barrier injury. SAP was established in rats by retrograde injection of sodium taurocholate (STC) into biliopancreatic duct. Transfection of miR-99a mimic was conducted 24 h before the SAP establishment. Histological properties of pancreatic and intestinal tissues were observed by hematoxylin–eosin staining. The serum levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, procalcitonin (PCT), endotoxin (ET), and diamine oxidase (DAO) were measured by enzyme-linked immunosorbent assay. The expressions of miR-99a, NADPH oxidase (NOX)4, zonula occludens (ZO)-1, occludin, and claudin-1 in pancreatic and the intestinal tissue were determined by quantitative reverse transcription polymerase chain reaction or Western blot. STC injection damaged pancreatic and intestinal tissues of the rats. During the model construction, the serum levels of IL-1β, TNF-α, PCT, ET, and DAO were increased, whereas miR-99a expression in pancreatic and intestinal tissues of the rats was decreased. miR-99a mimic alleviated SAP-induced histological abnormality of pancreatic and intestinal tissues; moreover, it reversed the serum levels of IL-1β, TNF-α, PCT, ET, and DAO increased by SAP, decreased SAP-increased NOX4 expression and increased the expressions of ZO-1, occludin, and claudin-1 previously decreased by SAP in pancreatic and the intestinal tissues. Thus, overexpressed miR-99a could alleviate intestinal mucosal barrier injury in rats with SAP.

中文翻译：

---

miR-99a过表达减轻重症急性胰腺炎大鼠肠道黏膜屏障损伤

重症急性胰腺炎(severeacute pancreatitis,SAP)以起病急、病死率高为特征，并发全身炎症反应综合征。本研究探讨了 SAP 诱导肠黏膜屏障损伤的分子机制。通过将牛磺胆酸钠 (STC) 逆行注射到胆胰管中，在大鼠中建立 SAP。在 SAP 建立前 24 小时进行 miR-99a 模拟物的转染。通过苏木精-伊红染色观察胰腺和肠组织的组织学特性。采用酶联免疫吸附法测定血清白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α、降钙素原（PCT）、内毒素（ET）和二胺氧化酶（DAO）水平。miR-99a、NADPH 氧化酶 (NOX)4、封闭小带 (ZO)-1、occludin、通过定量逆转录聚合酶链反应或蛋白质印迹法测定胰腺和肠组织中的claudin-1和claudin-1。STC注射损伤了大鼠的胰腺和肠组织。模型构建过程中，大鼠血清IL-1β、TNF-α、PCT、ET、DAO水平升高，而miR-99a在大鼠胰腺和肠组织中的表达降低。miR-99a 模拟物减轻了 SAP 诱导的胰腺和肠道组织的组织学异常；此外，它逆转了 SAP 增加的血清 IL-1β、TNF-α、PCT、ET 和 DAO 水平，降低了 SAP 增加的 NOX4 表达，并增加了先前降低的 ZO-1、occludin 和 claudin-1 的表达胰腺和肠组织中的 SAP。因此，