Effect of ulinastatin for hyperoxia-induced lung injury in neonatal mice models
Xu Fengdan, Deng Wenlong, Wu Wenshen, et al
1. Newborn Care Center, Dongguan Children’s Hospital, Affiliated to Guangdong Medical University, Guangdong, Dongguan 523325, China; 2. Intensive Care Unit, the Third People’s Hospital of Dongguan, Guangdong, Dongguan 523326, China; 3. Newborn Care Center, Bayi Children's Hospital, the Seventh Medical Center of PLA General Hospital, Department of Pediatrics, Chinese PLA General Hospital, Beijing 100700, China
Abstract: 【Abstract】ObjectiveTo study the effect of ulinastatin (UTI) for hyperoxia-induced lung injury in neonatal mice, and discuss its mechanism of action preliminarily. Methods Kunming mice at 2 days after birth were randomly divided into air group (46 mice) and hyperoxia group (46 mice), which were fed in air or 55% - 65% oxygen for 21 days respectively, 9 mice were randomly selected as the air control group (n=9), the high-oxygen group was randomly divided into the high-oxygen control group (n=9), the low-dose UTI treatment group (n=9), the middle-dose UTI treatment group (n=9), and the high-dose UTI treatment group (n=9) after successful modeling. 10,000 U/kg, 50,000 U/kg and 100 000 U/kg of UTI was injected through in abdomen every day to the low-dose UTI treatment group and the middle-dose UTI treatment group and the high-dose UTI treatment group respectively, once per day, 21 days in a row, while the air control group and the high-oxygen control group received the same dose of normal saline. Weights and status of rats were recorded. Animals in each group were sacrificed to observe the appearance of lung tissue and calculate the ratio of wet/dry weight of lung tissue. The pathological structure of lung tissue was observed by HE staining, and the expression level of (tumor necrosis factor-α, TNF-α) and the infiltration of macrophages in lung tissue were observed by immuno-histochemical staining. The protein levels of SOD and MDA were assessed using Western blot analysis. Statistical methods were carried out byt-test and χ2 test. Results Body weight of mice in UTI treatment group grew faster than that in the highoxygencontrol group, especially for the high-dose UTI treatment group, there was statistical significancein two groups（P<0.05）. UTI treatment could reduce obviously hyperoxia-induced lung tissue structure disorder macrophage infiltration, inflammatory response and pulmonary edema, attenuated the W/D weight ratio, down-regulated the levels of TNF-α and inhibited macrophage infiltration, especially for the high-dose UTI treatment group. But UTI treatment group had no significant effect on the levels of pulmonary SOD and MDA levels compared with hyperoxic control group at 21 day treatment. Conclusion UTI therapy may be effective in the prevention of hyperoxia-induced lung injury in newborn mice, which may be achieved mainly by anti-inflammatory responses and its anti-inflammatory effects are dose-dependent.
2021, Vol. 9 
