The mechanism of hyperbaric oxygen regulating HMGB1 in the prevention and treatment of encephalopathy after acute CO poisoning

Abstract

Objective: To study the expression of high mobility group protein 1 (HMGB1) in the brain of rats after hyperbaric oxygen (HBO) treatment of acute carbon monoxide poisoning (DEACMP) , and to explore the mechanism of HBO in the prevention and treatment of DEACMP pathological process by regulating HMGB1. Methods: 108 SD rats were randomly divided into control group (NC group) and co group (CO group) . HBO treatment group (HBO group) , 48 rats in each group. Co group and HBO group were used to establish CO poisoning model, HBO group were treated with hyperbaric oxygen once a day. Water maze test was used to detect and analyze the memory retention ability of three groups of rats in 3 d, 7 d, 14 d. ELISA was used to detect the plasma concentration of HMGB1、IL-6、TNF-α in three groups of rats on the 1 d, 3 d, 7 d, 14 d, 21 d Concentration. Western blotting was used to detect the expression of HMGB1 and Caspase-3 in the brain of the three groups on the 1 d, 3 d, 7 d, 14 d, 21 d. TUNEL staining was used to detect the apoptosis of hippocampal neurons in the three groups. Results: Compared with NC group, the average escape latency of rats in CO group and HBO group was significantly prolonged, and the activity time of platform quadrant in CO group was significantly shortened on 14 d and 21 d (P<0.05) ; compared with CO group, the average escape latency of HBO group on 7 d, 14 d and 21 d was significantly shortened (P<0.05) . Compared with NC group, plasma HMGB1 in CO group and HBO group were significantly increased (P<0.05) ; after 3 days, HBO group was significantly lower than co group, the difference was statistically significant (P<0.05) . The levels of IL-6 and TNF-α in HBO group and co group increased rapidly and then decreased gradually. The increased levels of IL-6 and TNF-α in HBO group were significantly lower than those in CO group (P<0.05) . Compared with NC group, the expression of HMGB1 and Caspase-3 in CO group was significantly increased on 3 d, 7 d and 14 d (P<0.05) ; the expression of HMGB1 and Caspase-3 in HBO group was significantly increased on 3 d, 7 d, 14 d and 21 d (P<0.05) ; compared with CO group, the expression of HMGB1 and Caspase-3 in HBO group decreased significantly on 3 d, 7 d, 14 d and 21 d (P<0.05) . The apoptotic index of nerve cells in CO group began to increase at 3 days, which was significantly different from that of NC group (P<0.05) , and the difference was still statistically significant on 21 d (P<0.05) ; the apoptotic index of nerve cells in HBO group was slightly increased, but there was no significant difference compared with NC group (P>0.05) , and the apoptotic index of 3 d, 7 d, 14 d and 21 d in HBO group was significantly lower than that in CO group (P<0.05) . Conclusion: acute CO poisoning can induce the release of HMGB1 and a variety of inflammatory factors. HMGB1 can promote the apoptosis of nerve cells after acute CO poisoning by up regulating the expression of caspase-3 protein, and participate in the pathological process of DEACMP. HBO can down regulate the expression of HMGB1, IL-6, TNF-α and caspase-3 protein, inhibit the apoptosis of nerve cells, and play a protective role on nerve cells.