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Ulinastatin Reduces the Severity of Intestinal Damage in the Neonatal Rat Model of Necrotizing Enterocolitis

Shuxia Liang, Panjian Lai, Xiaobing Li, Jie Xu, Yunguang Bao, Yuanshu Fang, Mingxing Ding

Department of Ophthalmology, Jinhua Hospital of Zhejiang University, Jinhua, Zhejiang, China (mainland)

Med Sci Monit 2019; 25:9123-9130

DOI: 10.12659/MSM.919413

Available online:

Published: 2019-12-01

BACKGROUND: Ulinastatin is a protease inhibitor derived from urine that has shown anti-inflammatory effects in human disease, including in sepsis. Necrotizing enterocolitis (NEC) is a common gastrointestinal disease in premature infants. Our aim was to explore the effects of ulinastatin on a neonatal NEC rat model.
MATERIAL AND METHODS: Forty-five neonatal rats were divided into 3 groups: normal control; NEC+sepsis-induced kidney injury (SIRS); NEC/SIRS+ulinastatin. The NEC/SIRS model was induced by injection of intraperitoneal saline, enteral formula feeding, hypoxia-hyperoxide, and cold stress exposure. The NEC/SIRS neonatal rats were perfused with ulinastatin at a dose of 10 000 u/kg/day. Giemsa staining and hematoxylin and eosin (H&E) were performed to evaluate the severity of intestinal damage. To assess intestinal cell apoptosis, we examined the expression of caspase-3 by TUNEL staining and western blot analysis. Intestinal levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-alpha) were examined using ELISA assay.
RESULTS: Rats in the NEC treated with ulinastatin group had better physiological status and histological score compared to the NEC/SIRS group. Ulinastatin reduced NEC-induced weight loss. Macroscopic and microscopic morphology analyses showed that rats in the NEC treated with ulinastatin group had lower severity of intestinal damage compared to the NEC/SIRS group. TUNEL staining and caspase-3 expression detection results revealed that ulinastatin significantly inhibited intestinal cell apoptosis of NEC. Furthermore, ulinastatin decreased the intestinal levels of IL-1ß, IL-6, and TNF-alpha in NEC.
CONCLUSIONS: Ulinastatin could ameliorate the severity of intestinal damage in NEC and possess anti-apoptosis and anti-inflammation effects.

Keywords: Apoptosis, Enterocolitis, Necrotizing, Infant, Newborn, Inflammation