异氟烷延迟治疗可减轻脂多糖和干扰素γ诱导的小鼠小胶质细胞激活和损伤。
Delayed treatment with isoflurane attenuates lipopolysaccharide and interferon gamma-induced activation and injury of mouse microglial cells.
作者信息
Kim Jie-Ae, Li Liaoliao, Zuo Zhiyi
机构信息
Department of Anesthesiology, University of Virginia, Charlottesville, Virginia 22908-0710, USA.
出版信息
Anesthesiology. 2009 Sep;111(3):566-73. doi: 10.1097/ALN.0b013e3181af5b3d.
BACKGROUND
Isoflurane pretreatment can induce protection against lipopolysaccharide and interferon gamma (IFNgamma)-induced injury and activation of mouse microglial cells. This study's goal was to determine whether delayed isoflurane treatment is protective.
METHODS
Mouse microglial cells were exposed to various concentrations of isoflurane for 1 h immediately after the initiation of lipopolysaccharide (10 or 1000 ng/ml) and IFNgamma (10 U/ml) stimulation or to 2% isoflurane for 1 h at various times after initiation of the stimulation. Nitrite production, lactate dehydrogenase release, and cell viability measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were assessed after stimulation with lipopolysaccharide and IFNgamma for 24 h. Inducible nitric oxide synthase (iNOS) protein expression was quantified by Western blotting. The iNOS expression in mouse brain was also studied.
RESULTS
Isoflurane applied 0 and 2 h after the initiation of lipopolysaccharide and IFNgamma stimulation improved cell viability. Isoflurane at 2%, but not at 1 or 3%, reduced the lipopolysaccharide and IFNgamma-induced nitrite production and decreased cell viability. Aminoguanidine, an iNOS inhibitor, also attenuated this decreased cell viability. Chelerythrine and bisindolylmalemide IX, protein kinase C inhibitors, abolished isoflurane effects on cell viability and iNOS expression after lipopolysaccharide and IFNgamma application. Isoflurane also decreased lipopolysaccharide-induced iNOS expression in mouse brain. Late isoflurane application to microglial cells reduced lipopolysaccharide and IFNgamma-induced lactate dehydrogenase release that was not inhibited by aminoguanidine.
CONCLUSIONS
These results suggest that delayed isoflurane treatment can reduce lipopolysaccharide and IFNgamma-induced activation and injury of microglial cells. These effects may be mediated by protein kinase C.
背景
异氟烷预处理可诱导对脂多糖和干扰素γ（IFNγ）诱导的小鼠小胶质细胞损伤及激活的保护作用。本研究的目的是确定延迟给予异氟烷治疗是否具有保护作用。
方法
在脂多糖（10或1000 ng/ml）和IFNγ（10 U/ml）刺激开始后立即将小鼠小胶质细胞暴露于不同浓度的异氟烷中1小时，或在刺激开始后的不同时间将其暴露于2%异氟烷中1小时。在用脂多糖和IFNγ刺激24小时后，评估亚硝酸盐生成、乳酸脱氢酶释放以及通过3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐法测定的细胞活力。通过蛋白质印迹法定量诱导型一氧化氮合酶（iNOS）蛋白表达。还研究了小鼠脑中的iNOS表达。
结果
在脂多糖和IFNγ刺激开始后0小时和2小时给予异氟烷可提高细胞活力。2%的异氟烷可降低脂多糖和IFNγ诱导的亚硝酸盐生成，但1%或3%的异氟烷则不能，且2%异氟烷会降低细胞活力。iNOS抑制剂氨基胍也减弱了这种细胞活力的降低。蛋白质激酶C抑制剂白屈菜红碱和双吲哚基马来酰胺IX消除了异氟烷对脂多糖和IFNγ作用后细胞活力和iNOS表达的影响。异氟烷还降低了脂多糖诱导的小鼠脑中iNOS的表达。对小胶质细胞延迟给予异氟烷可减少脂多糖和IFNγ诱导的乳酸脱氢酶释放，而氨基胍对此无抑制作用。
结论
这些结果表明，延迟给予异氟烷治疗可减少脂多糖和IFNγ诱导的小胶质细胞激活和损伤。这些作用可能由蛋白激酶C介导。
Zotero 插件