Effect of combination therapy with propofol and hydrogen-rich saline on organ damage and cytokines in a murine model of sepsis

Abstract:

Objective: To investigate the effect of combining propofol with hydrogen on organ damage and inflammation of sepsis in cecal ligation and puncture (CLP) mice model.

Methods: One hundred and forty male C57BL/6 mice were randomly divided into groups (n = 28): sham group, CLP group, propofol group, H2 group, and propofol and H2 group. The sepsis was induced by CLP operation. Mice in sham group did the same operation with ligation and puncture. The mice of propofol group and propofol and H2 group were given 50 mg/kg propofol through tail vein at 1 hour and 6 hours after CLP and the mice of H2 group and propofol and H2 group were given 5 mL/kg H2-rich saline i.p. at 1 hour and 6 hours after CLP. The survival rates were observed during 7 days in twenty mice of each group. Inferior vena cava blood and part lung, liver and kidney tissue were collected for detection of the concentration of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and high mobility group box 1 (HMGB1) at 24 hours after CLP in the 40 animals left (each n = 8). Then, the rest tissue of lung, liver and kidney tissue were harvested to test histopathology and histological score.

Results: The 1, 2, 3, 5, 7 days survival rate of septic mice were 80%, 40%, 20%, 10%, and 0%, respectively. The survival rate of animals increased significantly after propofol or hydrogen-rich treatment, and the combined treatment can further increase survival rate to 90%, 75%, 60%, 55%, and 55%, respectively. Compared with the sham group, inflammatory factors were significantly increased in blood and organ tissues, cell degeneration, necrosis, congestion and inflammatory cell infiltration in lung, liver and kidney, and tissues histological scores were significantly increased. The levels of inflammatory factors were reduced in blood and tissues, cell degeneration, necrosis, congestion and inflammatory cell infiltration were alleviated in lung, liver and kidney, and tissues histological scores were decreased after propofol or hydrogen-rich treatment compared with CLP group; these indicators were further improved in propofol and H2 group compared with propofol group or H2 group [2, 3, 5, 7-day survival rate: 75% vs. 60%, 65%; 60% vs. 50%, 50%; 55% vs. 45%, 40%; 55% vs. 40%, 40%; blood TNF-α (ng/L): 367±74 vs. 612±132, 588±117; blood IL-1β (ng/L): 321±68 vs. 502±95, 476±86; blood HMGB1 (μg/L): 4.6±0.9 vs. 7.0±1.4, 6.8±1.3; lung TNF-α (ng/g): 307±70 vs. 512±132, 488±102; lung IL-1β (ng/g): 367±77 vs. 571±108, 466±89; lung HMGB1 (μg/g): 5.1±1.0 vs. 7.8±1.7, 7.1±1.5; liver TNF-α (ng/g): 247±57 vs. 431±112, 389±87; liver IL-1β (ng/g): 267±58 vs. 417±85, 399±76; liver HMGB1 (μg/g): 4.2±1.1 vs. 7.1±1.6, 6.6±1.2; kidney TNF-α (ng/g): 257±41 vs. 480±89, 448±82; kidney IL-1β (ng/g): 258±39 vs. 409±68, 411±66; kidney HMGB1 (μg/g): 3.9±0.7 vs. 6.8±1.2, 5.7±1.0; histological scores: lung: 1.22±0.28 vs. 2.61±0.49, 2.58±0.44; liver: 1.38±0.32 vs. 2.76±0.51, 2.62±0.46; kidney: 1.19±0.25 vs. 2.43±0.41, 2.36±0.40; all P < 0.05]. Conclusions: Both propofol and H2 can improve the survival rate of sepsis, reduce tissue damage and the release of cytokines, and combined application of the two treatment was better.