严重烧伤早期小鼠腹腔巨噬细胞糖皮质激素受体变化及安定-氯胺酮对其影响

Expression changes of glucocorticoid receptor in peritoneal macrophages and effect of diazepam-ketamine on glucocorticoid receptor in severe burned mice

目的 观察严重创伤早期小鼠腹腔巨噬细胞糖皮质激素受体 (GR)蛋白表达的变化 ,并探讨安定 氯胺酮对其变化的影响 ,为安定 氯胺酮在创伤应激中的作用提供可靠实验依据。方法 95只成年健康昆明小鼠 ,随机分为正常对照组、烧伤组、安定 氯胺酮处理组、烧伤后安定 氯胺酮处理组 ,应用Westernblot技术检测各组小鼠处理后早期 2 4h内不同时期腹腔巨噬细胞GR的蛋白表达水平。结果 小鼠严重烧伤后 30min ,腹腔巨噬细胞中GR的表达就已经开始降低 ,在 6h达到最低 ,显著低于正常对照组 ,12h时逐渐回升 ,但在 2 4h时仍低于正常。而安定 氯胺酮组GR的表达水平无显著差异 ,在严重烧伤后应用安定 氯胺酮能明显地抑制GR蛋白表达水平的降低 ,烧伤后安定 氯胺酮处理组各时相点与正常对照组相比无显著差异。结论 严重烧伤可引起小鼠腹腔巨噬细胞GR表达水平的下降 ,而单纯应用安定 氯胺酮对小鼠腹腔巨噬细胞GR的表达水平无明显影响 ,在严重烧伤后应用安定 氯胺酮能显著抑制GR水平的下调 ,故安定 氯胺酮可能部分改善小鼠严重烧伤诱发的应激状态。

Objective To observe the expression changes of glucocorticoid receptor (GR) in the peritoneal macrophages, and to investigate the effect of diazepam-ketamine on the expression changes of glucocorticoid receptor in peritoneal macrophages in severe burned mice in order to provide experimental bases for the role of diazepam-ketamine in stress.Methods Experiments were performed on 95 healthy adult Kunming mice, weight 24g to 30g. The animals were randomly assigned to four groups including normal control group, severe burn injury group, diazepam-ketamine group and treatment of diazepam-ketamine after severe burn injury group. Western blot was used to detect the expressions of GR in the peritoneal macrophages in every group mice.Results The expression level of GR in peritoneal macrophages in mice was markedly declined from 30 min after severe burning, reached the lowest at 6h (significantly lower than the normal control), resumed to normal at 12h but was still lower than normal control after 24h. while there was no significant effect of diazepam-ketamine on the expression of GR in peritoneal macrophages in mice. The expression of GR in peritoneal macrophages in mice was evidently increased after treatment of diazepam-ketamine during 30 min to 24h after severe burn injury.Conclusion Severe burning can significantly decrease the expression of the GR in the peritoneal macrophages in mice. There was no significant effect of diazepam-ketamine on the expression of GR in normal mice. After severe burn injury of mice, the expression of the GR in the peritoneal macrophages was significant elevated by diazepam-ketamine. Diazepam-ketamine might partially improved the state of stress induced by severe burn injury in mice.