Dugan Amy L, Gregerson Karen A, Neely Alice, Gardner Jason, Noel Greg J, Babcock George F, Horseman Nelson D
Department of Research, Shriners Hospital Cincinnati, Ohio, USA.
J Burn Care Res. 2010 Jan-Feb;31(1):1-12. doi: 10.1097/BCR.0b013e3181cb8e82.
Psychological stress has a high incidence after burn injury, therefore, anxiolytic drugs are often prescribed. Unfortunately, to date, no burn study has investigated the effects of anxiolytic drugs on the ability to fight infection. This study was undertaken to determine if psychological stress, anxiety-modulating drugs, or both, alter survival following an infection. On day 0, 7-week-old male C57Bl/6 mice either received a 15% full-thickness flame burn or were sham treated (anesthesia and shaved), whereas controls received no treatment. Mice received midazolam (1 mg/kg intraperitoneally) or saline daily and were stressed by exposure to rat in a guinea pig cage or placed in an empty cage for 1 hour a day, beginning on postburn day 1. For the survival experiments, mice either received bacteria after 2 or 8 consecutive days of predator exposure and drug treatment, which continued daily for 7 days after inoculation. In a separate set of experiments, after eight daily injections of midazolam, mice were given lipopolysaccharide, bacteria, or saline and were killed 12 hours later. Mice that received midazolam had improved survival rates when compared with their saline-treated counterparts, and the protective effect was more significant the more days they received the drug. For most of the cytokines, the bacteria-induced increase was significantly attenuated by midazolam as was the amount of bacteria in the liver. The protective effect seems to be independent of the drug's anxiolytic activity as there were no significant differences in survival between the predator-stressed and the nonstressed mice. The mechanisms responsible for the protective effect remain to be elucidated.
烧伤后心理应激的发生率很高,因此,常常会开具抗焦虑药物。遗憾的是,迄今为止,尚无烧伤研究调查过抗焦虑药物对抗感染能力的影响。本研究旨在确定心理应激、焦虑调节药物或两者是否会改变感染后的存活率。在第0天,7周龄的雄性C57Bl/6小鼠要么接受15%的全层火焰烧伤,要么接受假处理(麻醉和剃毛),而对照组不接受任何处理。从烧伤后第1天开始,小鼠每天接受咪达唑仑(1 mg/kg腹腔注射)或生理盐水,并通过将其置于豚鼠笼中与大鼠接触或每天置于空笼中1小时来施加应激。在生存实验中,小鼠在连续2天或8天的捕食者暴露和药物处理后接种细菌,接种后每天继续处理7天。在另一组实验中,在每天注射咪达唑仑8次后,给小鼠注射脂多糖、细菌或生理盐水,并在12小时后处死。与接受生理盐水处理的小鼠相比,接受咪达唑仑的小鼠存活率有所提高,并且接受药物的天数越多,保护作用越显著。对于大多数细胞因子,细菌诱导的增加被咪达唑仑显著减弱,肝脏中的细菌数量也是如此。保护作用似乎与药物的抗焦虑活性无关,因为在捕食者应激小鼠和非应激小鼠之间的存活率没有显著差异。负责保护作用的机制仍有待阐明。