Pathophysiological characteristics of hypoxic liver injury in sepsis rats at different time points and the protective effect of ulinastatin on sepsis rats

DING Lei; GONG Yihang; ZOU Baojia; LIU Xialei; ZHANG Baimeng; LI Jian

doi:10.3969/j.issn.1002-266X.2019.04.008

Abstract：Objective To construct the cecal ligation puncture (CLP) sepsis rat models to study the pathophysiological changes in different time points and to investigate the protective effect of ulinastatin (UTI) on the liver of CLP rats.Methods SD rats were divided into 4 groups: the sham group, sham + UTI group, CLP group, and CLP + UTI group.Each group was divided into 5 subgroups based on CLP time (12, 24, 36, 48, and 72 h). Murine sepsis score (MSS) was used to evaluate the general condition of rats. We performed the blood gas analysis on rats and measured the levels of hypoxia inducible factor-1α (Hif-1α), ALT, AST, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in each group at different time points. Results The indexes of the CLP group and CLP + UTI group changed significantly. Mean arterial pressure (MAP) decreased at 36 h after CLP (P ＜ 0. 05). Blood lactate (Lac) level and MSS of rats in the CLP group increased significantly (both P ＜ 0. 05). The arterial oxygen pressure (PaO 2) decreased at 36 h after CLP and reached the lowest level at 72 h. The arteriovenous partial pressure difference (APPD) of rats also showed a similar trend (P ＜ 0. 05).The levels of IL-6 and TNF-α increased significantly in the CLP group and CLP + UTI group (both P ＜ 0. 05), but AST increased only at 72 h after CLP as compared with that of the sham group (P＞ 0. 05), and no significant change was found in ALT after CLP. UTI could improve the pathophysiological changes of CLP rats, especially at 48 and 72 h after CLP.Conclusions Multiple pathophysiological changes occur in sepsis rats induced by CLP in different periods. The early stage of sepsis in CLP rats progresses slowly and the condition deteriorates rapidly after 36 h. Systematic hypoxia and decreased oxygen uptake of liver cells are the main causes of liver injury in sepsis. UTI can play an protective role in inhibit the late stages of CLP sepsis-induced hypoxic liver injury, but it can not reverse the progress of inflammation.