Delayed treatment with isoflurane attenuates lipopolysaccharide and interferon gamma-induced activation and injury of mouse microglial cells.
Delayed treatment with isoflurane attenuates lipopolysaccharide and interferon gamma-induced activation and injury of mouse microglial cells.
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DOI：
10.1097/aln.0b013e3181af5b3d
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发表时间：
2009-09
期刊：
影响因子：
8.8
通讯作者：
Zuo Z
中科院分区：
文献类型：
--
作者：
Kim JA;Li L;Zuo Z
异氟醚预处理对脂多糖和γ干扰素（IFNγ）诱导的小鼠小胶质细胞损伤和活化具有保护作用。在这里，我们确定延迟异氟烷治疗是否具有保护作用。在开始脂多糖（10或1000 ng/ml）和IFNγ（10 U/ml）刺激后立即将小鼠小胶质细胞暴露于不同浓度的异氟烷1 h，或在开始刺激后的不同时间暴露于2%异氟烷1 h。用脂多糖和IFNγ刺激24 h后，测定亚硝酸盐的产生、乳酸脱氢酶的释放和细胞活力，用Western blotting法测定诱导型一氧化氮合酶（iNOS）蛋白的表达。同时观察小鼠脑内iNOS的表达。在脂多糖和IFNγ刺激开始后0和2小时应用异氟烷可改善细胞活力。2%的异氟烷可减少脂多糖和IFNγ诱导的亚硝酸盐生成，并降低细胞活力，但1%或3%的异氟烷则不能。氨基胍，一种iNOS抑制剂，也减弱了这种降低的细胞活力。白屈菜红碱和双吲哚马来酰亚胺IX，蛋白激酶C抑制剂，消除异氟烷对细胞活力和iNOS表达的影响后，脂多糖和IFNγ的应用。异氟醚还降低脂多糖诱导的小鼠脑中iNOS的表达。晚期异氟烷应用于小胶质细胞可减少脂多糖和IFNγ诱导的乳酸脱氢酶释放，而氨基胍不抑制该释放。我们的研究结果表明，延迟异氟醚治疗可以减少脂多糖和IFNγ诱导的小胶质细胞的活化和损伤。这些作用可能由蛋白激酶C介导。
Isoflurane pretreatment can induce protection against lipopolysaccharide and interferon γ (IFNγ)-induced injury and activation of mouse microglial cells. Here, we determine whether delayed isoflurane treatment is protective. Mouse microglial cells were exposed to various concentrations of isoflurane for 1 hr immediately after the initiation of lipopolysaccharide (10 or 1000 ng/ml) and IFNγ (10 U/ml) stimulation or to 2% isoflurane for 1 hr 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 IFNγ for 24 hr. Inducible nitric oxide synthase (iNOS) protein expression was quantified by Western blotting. The iNOS expression in mouse brain was also studied. Isoflurane applied 0 and 2 hr after the initiation of lipopolysaccharide and IFNγ stimulation improved cell viability. Isoflurane at 2%, but not at 1 or 3%, reduced the lipopolysaccharide and IFNγ-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 IFNγ application. Isoflurane also decreased lipopolysaccharide-induced iNOS expression in mouse brain. Late isoflurane application to microglial cells reduced lipopolysaccharide and IFNγ-induced lactate dehydrogenase release that was not inhibited by aminoguanidine. Our results suggest that delayed isoflurane treatment can reduce lipopolysaccharide and IFNγ-induced activation and injury of microglial cells. These effects may be mediated by protein kinase C.