Intraintestinal administration of ulinastatin protects against sepsis by relieving intestinal damage.
Intraintestinal administration of ulinastatin protects against sepsis by relieving intestinal damage.
复制标题
DOI：
10.1016/j.jss.2016.11.061
复制
发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Bingchang Yang;Min Gao;Kangkai Wang;Yu Jiang;Yue Peng;Huali Zhang;Mingshi Yang;Xianzhong Xiao
中科院分区：
文献类型：
--
作者：
Bingchang Yang;Min Gao;Kangkai Wang;Yu Jiang;Yue Peng;Huali Zhang;Mingshi Yang;Xianzhong Xiao
背景静脉注射乌司他丁（UTI）是一种广谱蛋白酶抑制剂，在亚洲已在实验基础上用于严重脓毒症患者。然而，肠内给予UTI对脓毒症肠道和多器官损害的影响尚未报道。采用盲肠结扎穿孔法建立大鼠脓毒症模型，比较经十二指肠瘘肠内注射UTI和腹腔注射UTI对脓毒症病理生理变化的影响。肠内给予UTI（1）显著改善脓毒症大鼠的存活率，（2）显著降低血清肿瘤坏死因子-α、白细胞介素-1 β、白细胞介素-6以及肠损伤生物标志物二胺氧化酶、D-乳酸和异硫氰酸荧光素-葡聚糖4的水平，（3）显著降低脓毒症大鼠的肠显微镜和超微结构损伤。此外，肠内给予UTI的保护作用明显优于腹腔内给予UTI。本研究首次揭示了肠内给予蛋白酶抑制剂UTI可以通过抑制蛋白酶引起的肠壁自身消化来减轻脓毒症大鼠的全身炎症反应和多器官功能障碍，提供了新的研究思路和方法通过肠内施用UTI治疗脓毒症的实验证据。
BackgroundIntravenous administration of ulinastatin (UTI), a broad spectral protease inhibitor, has been used on an experimental basis with severe sepsis patients in Asia. However, the effects of intraintestinal administration of UTI on intestinal and multiple organ damage in sepsis have not been reported.Materials and methodsIn this study, we established a sepsis model in rats using cecal ligation and puncture and compared the effects of intraintestinal administration of UTI through an artificial fistula of duodenum and intraperitoneal administration of UTI on the pathophysiological changes of sepsis.ResultsIt was found that intraintestinal administration of UTI (1) significantly improved the survival of septic rats, (2) significantly reduced the serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 as well as intestinal injury biomarkers diamine oxidase, D-lactic acid, and fluorescein isothiocyanate-dextran 4, and (3) significantly reduced intestinal microscopic and ultrastructural damage of septic rats. In addition, the protective effects of intraintestinal administration of UTI were significantly better than those of intraperitoneal administration of UTI.ConclusionsOverall, the present study for the first time revealed that intraintestinal administration of protease inhibitor UTI could reduce systemic inflammatory responses and multiple organ dysfunction in rats with sepsis by inhibiting autodigestion of intestinal wall due to proteases and provided new research ideas and experimental evidences for treatment of sepsis by intraintestinal administration of UTI.