清醒小鼠严重颅脑闭合性撞击伤后大脑皮质和肝脏糖皮质激素受体蛋白表达变化的差异  

Expression difference of cerebral cortex and liver glucocorticoid receptors at protein level following severe closed traumatic brain injury in awake mice

作　　者：屈强[1] 史忠[2] 粟永萍[3] 

机构地区：[1]泸州医学院附属医院麻醉科,646000 [2]第三军医大学附属新桥医院急诊科 [3]第三军医大学全军复合伤研究所、创伤、烧伤与复合伤国家重点实验室

出　　处：《中华创伤杂志》2011年第4期366-369,共4页Chinese Journal of Trauma

基　　金：基金项目：国家重点基础研究发展规划资助项目（G1999054201）

摘　　要：目的 研究小鼠闭合性严重颅脑外伤后大脑皮质糖皮质激素受体（glucocorticoid receptors,GR）蛋白水平的变化与外周肝脏GR蛋白水平的变化、血清皮质醇、促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）变化的关系.方法 利用BIM-Ⅲ型小型多功能动物撞击机对小鼠清醒致伤,于致伤后30 min、2 h、8 h、24h、48 h、72 h采用Western blot免疫印迹法检测大脑皮质和肝脏GR的蛋白水平的变化,ELISA法检测各组外周血清中ACTH含量,放免法检测皮质醇含量.结果 致伤后2 h大脑皮质和肝脏GR均出现蛋白水平表达降低,8 h后呈现恢复趋势,肝脏GR至72 h仍未完全正常;而大脑皮质GR从致伤后24 h再次呈现持续的表达降低.外周血中ACTH、皮质醇较对照组有明显升高,均具有的两个峰值特征,但是两者的高峰期并不完全吻合.结论 严重颅脑外伤后中枢和外周组织均存在糖皮质激素抵抗,两者的变化具有时相差异性.Objective To study the relationship of expression of central cortex glucocorticoid receptor （GR） at protein level with GR expression in the liver at protein level and with changes of serum cortisol and adrenocorticotropic hormone （ACTH） following severe closed traumatic brain injury （TBI） in mice. Methods Severe TBI was established in awake mice by using a BIM-Ⅲ biomechanical machine. At 0.5, 2, 8, 24, 48 and 72 hours after TBI, the total cytosolic GR in the cortex and liver were detected with Western blotting. Levels of serum ACTH and cortisol were measured by ELISA technique and radio-immunological assay （RIA） respectively. Results The expression of GR both in the cortex and liver were obviously down-regulated at protein levels at 2-72 hours after TBI and increased slowly eight hours after injury. The GR in the liver showed no recovery at 72 hours after injury and that in the cortex was decreased continually at 24 hours after injury. Serum ACTH and cortisol levels were increased markedly compared with control group, when there were two different peaks in the observation curve.Conclusion There is glucocorticoid resistance both in the central and peripheral tissues after severe closed TBI in the awake mice, which changes in a time-dependent manner.

关 键 词：脑损伤 受体 糖皮质激素类 促肾上腺皮质激素 

分 类 号：R686[医药卫生—骨科学]