严重颅脑外伤患者早期外周血TNF-α、IL-1β、ACTH、皮质醇和淋巴细胞GR的变化

Changes of TNF-α,IL-1β and cortisol in serum and hepatic GR following severe traumatic brain injury

目的 研究严重颅脑外伤患者早期外周血中白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）、促肾上腺皮质激素（ACTH）、皮质醇水平的变化与血中淋巴细胞糖皮质激素受体（GR）变化的关系,以及氯胺酮和咪唑安定的影响.方法 选择严重颅脑外伤成年患者,随机分成致伤治疗组和致伤对照组,取正常人作为正常对照组.治疗组入院后给予氯胺酮加咪唑安定.检测各患者血液中ACTH、皮质醇、TNF-α、IL-1β含量,分离淋巴细胞检测GR蛋白水平的变化.结果 严重颅脑外伤患者早期IL-1β、TNF-α、ACTH、皮质醇较正常对照组均明显升高,致伤治疗组和致伤对照组间GLS评分3～5分的组间无差异,6～8分的组间有明显差异;血中淋巴细胞GR致伤后明显降低,GLS评分6～8分的治疗组GR降低明显好于致伤对照组.结论 严重颅脑外伤患者伤后存在糖皮质激素抵抗现象,与TNF-α、IL-1β两种炎性细胞因子关系密切;应用氯胺酮加咪唑安定后能明显改善GLS评分6～8分患者的GR降低.

Objective To observe the changes of TNF-α,IL-1β, ACTH, cortisol in serum and lymphocytic glucocorticoid resistant（GR） following severe traumatic brain injury（TBI）. Methods The adult patients with severe TBI were randomly distributed to group Ⅰ （treated by ketamine and midazolam）,group Ⅱ （no intervening） and group Ⅲ （normal contral）. At 1h,2-4h,6-8h after TBI, ACTH, cytokine levels of TNF-α and IL-1β were measured by ELISA and radioimmuolgical assay （RIA）, serum cortisol levels were determined,and total cytosolic GR in lymphocyte were detected with Western blotting. Results Serum ACTH, cortisol, TNF-α, IL-1β levels increased markedly, and there were two acmes in the observing curve. The lymphocytic GR was obviously down-regulated at protein levels after TBI, but only decreased more markedly in group Ⅱ than in group I in Glasgow score 6-8 groups. Conclusion There is glucocorticoid resistant after severe TBI in human. There is inseparable relation of TNF-α and IL-1β. Ketamine and midazolam are apparently effective for reducing GR.