Abstract: Objective To investigate the effects of high mobility group box 1(HMGB1) on apoptosis of polymorphonuclear neutrophil(PMN) in LPS-induced acute respiratory distress syndrome and observe the effect of sodium butyrate(SB) treatment on septic rats. Methods Ninety adult male Sprague-Dawley(SD) rats were randomly assigned to one of three groups: normal saline control group(NS group)(n=6), lipopolysaccharides(LPS) group(LPS group)(n=42), sodium butyrate group(SB group) (n=42). At different time points(0.5, 1, 2, 6, 12, 24, 48 h), rats assigned to LPS group received 5 mg/kg LPS by i.p. injection. Rats in SB groups were injected 5 mg/kg LPS and 500 mg/kg sodium butyrate after half an hour by i.p. injection. Rats in NS group received 1 ml normal saline by i.p. injection. PMNs in peripheral blood and the bronchoalveolar lavage fluid(BALF) of the left lung were collected at different time?蛳points. The middle of the right lung was taken out to detect the expression of HMGB1 mRNA in lung tissues. At 12 h after LPS injected(peripheral blood and BALF was collected and the expression of HMGB1 mRNA was detected in NS group), all the three groups taken the left lung to collect BALF, the inferior lobe of right lung to determinate the wet/dry weight ratio(W/D), the superior lobe of right lung to detect the histopathologic changes of lung. At 24, 48 h after LPS injected, both LPS and SB group detected the W/D and the histopathologic changes as the same way. Results With the administration of LPS, the expression of HMGB1 mRNA were significantly higher than that in NS group(P<0.05). The early-phase apoptosis rate are similar, the late-phase apoptosis of neutrophil in bronchoalveolar lavage fluid of LPS was decreased but in peripheral blood was increased(P<0.05) in LPS group compared with NS group. The neutrophil percentage of LPS 12 h group was higher than that in NS group[(49.1±6.8),(2.7±0.5)](P<0.01). Pathological examination showed that the normal structure of lung was destroyed badly after LPS injection, including infra-alveolar hemorrhage,interstitial edema, alveolar collapse and massive inflammatory cells infiltration. The lung water content of LPS 12 h group was significantly increased[(6.71±0.12),(4.18±0.26)](P<0.05). However, sodium butyrate treatment can significantly reduce the expression of HMGB1 mRNA, and all the above indicators in SB group significantly lower than LPS group(P<0.05). Conclusions HMGB1 mRNA expression in acute respiratory distress syndrome is late, but a long duration, SB has the potential therapeutic effect on HMGB1. HMGB1 may participate in the regulation of neutrophil mechanism.
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