Effects of Emulsified Sevoflurane and Ulinastatin on Liver and Lung Injury Induced by Bile Duct Ligation in Rats

Abstract

Backgroud: To investigate the effects and their mechanisms of emulsified sevoflurane and ulinastatin on liver and lung injury induced by obstructive jaundice in rats. Methods: For the in vivo study, male Sprague-Dawley rats were randomized into two parts. Part 1: Sham group, bile duct ligation (BDL) group, BDL and lipid vehicle infusion (BDL + V) group, BDL + ulinastatin (BDL + U) group, BDL + emulsified sevoflurane (BDL + E) group; Liver and lung function was examined by the concentrations of Total Bilirubin (TBIL), Alanine Transaminase (ALT), and lung arterial blood gas analysis. Liver and lung damage was estimated histologically with haematoxylin and eosin (HE) staining in liver and lung samples. F4/80, the molecular marker of activated macrophages, was assessed by immunohistochemistry (IHC). Part 2: Sham + Gadolinium chloride (GdCl3)group, BDL+GdCl3 group, BDL+U+GdCl3 group, BDL+E+ GdCl3 group. After the deletion of macrophages, liver and lung examinations were evaluated histologically with HE staining in GdCl3 treated rats. For the in vitro study, the RAW264.7 cell line was stimulated by the different treatments, then terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining), Hoechst 33342 staining and the expressions of apoptotic related genes were evaluated to further determine the protective effects of ulinastatin and emulsified sevoflurane. Results: Emulsified sevoflurane and ulinastatin therapies alleviated cholestatic liver and lung damage, inhibited the activation of macrophages in the liver and lung tissues, and improved the liver and lung functions. And they were also found to inhibit apoptosis pathways. Conclusions: Emulsified sevoflurane and ulinastatin treatments were proved to ameliorate BDL-induced cholestatic liver and lung injuries, which were related to the inactivation of the macrophages and the regulation of apoptosis pathways. The abovementioned mechanisms show new promising approach for the multi-organs injuries in the perioperative management.