氯胺酮对大鼠肺泡巨噬细胞胞内钙离子及活性氧的影响
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摘要
第一部分:氯胺酮对LPS刺激的大鼠肺泡巨噬细胞胞内钙离子及活性氧的影响
目的:研究氯胺酮对脂多糖(LPS)刺激的大鼠肺泡巨噬细胞一氧化氮(NO)、羟自由基(·OH)、超氧阴离子(O_2·~-)生成及胞内游离钙离子([Ca~(2+)]_i)的影响。
方法:体外培养的大鼠肺泡巨噬细胞系NR8383分为对照组(C组),LPS组(L组)及不同浓度氯胺酮预处理组(K1、K2和K3组)。L组、K1、K2和K3组均采用1 mg/L的LPS刺激,在刺激前分别给以磷酸盐缓冲溶液(PBS)、10、100和1000 gmol/L浓度氯胺酮预处理。C组用相同剂量的PBS处理。继续培养24小时后用试剂盒检测细胞培养上清液中NO、·OH及(超氧阴离子)O_2·~-水平,应用激光共聚焦法测定胞内游离钙离子的水平。
结果:L组NO、·OH、O_2·~-及胞内游离钙离子的水平显著高于C组;与L组相比,K2和K3组的NO、·OH、O_2·~-及胞内游离钙离子的水平显著降低;K2和K3组间无统计学差异。
结论:氯胺酮(100和1000μmol/L)对LPS所致的NR8383的NO、·OH、O_2·~-及胞内游离钙离子的的升高有抑制作用。
第二部分氯胺酮对卵蛋白激发的致敏大鼠离体肺泡巨噬细胞胞内钙和自由基的影响
目的:研究氯胺酮对OVA刺激的致敏大鼠肺泡巨噬细胞(AM)一氧化氮(NO)、羟自由基(·OH)、超氧阴离子(O_2·~-)生成及胞内游离钙离子([Ca~(2+)]_i)的影响。
方法:SD大鼠经皮下注射OVA致敏后行肺泡灌洗,分离纯化后得到体外培养的AM,经氯胺酮(10μM,100μm和1000μM)处理、OVA刺激后,测定细胞[ca~(2+)]_i并检测细胞培养上清液中一氧化氮(NO)、羟自由基(·OH)及O_2·~-水平。
结果:OVA刺激可引起致敏肺泡巨噬细胞[Ca~(2+)]_i增高及NO、·OH和O_2·~-的生成增多,氯胺酮对此具有抑制作用。
结论:氯胺酮可抑制OVA所致的氧化应激,其分子机制可能与[Ca~(2+)]_i相关。
Part One
Effects of ketamine on nitrogen monoxidum,oxygen Radicals and free intracellular calcium in Lipopolysaccharide-stimulated rat alveolar macrophage in vitro
Objective:To investigate the effects of ketamine on production of Nitric oxide(NO),hydroxy radical(·OH),superoxide anion(O_2·~-)and free intracellular calcium([Ca~(2+)]_i)in the rat alveolar macrophage cell line (NR8383)activated by Lipopolysaccharide(LPS).
Methods:Macrophage was distributed into five groups,group C, group L,group K1,group K2 and group K3.Group L,K1,K2 and K3 were stimulated with LPS.Before stimulation,Group L,K1,K2 and K3 were treated with phosphate buffer solution(PBS),10,100and 1000μmol/L ketamine.Group C was treated with PBS.The levels of NO,·OH and O_2·~- in the supernatant were assayed.The[Ca~(2+)]i level was measured with fluorescent intensity by laser scanning confocal microscope.
Results:The concentrations of NO,·OH,O_2·~-and[Ca~(2+)]_i in group L increased significantly(P＜0.01)when compared to Group C.The concentrations of NO,·OH and O_2·~- in Group K2,K3 were obviously lower than those of Group L(P＜0.05).There was no statistical difference between K2 and K3(P＞0.05).
Conclusions:Ketamine(100 and 1000μmol/L)can inhibit LPS-induced production of NO,·OH,O_2·~- and[Ca~(2+)]_i.
Part Two
Effects of Ketamine on OVA-induced the changes of Free Intracellular Calcium and Free-radical in Alveolar Macrophages in Vitro
Objective:To observe the effect of ketamine on OVA-induced the changes of free intracellular calcium([Ca~(2+)]_i)and free-radical in alveolar macrophages from sensitized rat in vitro.
Methods:Macrophages were collected from Bronchoalveolar Lavage fluid of OVA-sensitized Sprague-Damley rats and treated with ketamine of concentration at 10μM,100μM and 1000μM before challenge with 100μg/mL OVA.The production of nitric oxide(NO),hydroxy radical (·OH)and superoxide anion(O_2·~-)in the supematant of culture was assayed by kits and the[Ca~(2+)]_i of macrophages was measured with mean fluorescent intensity(MFI)by laser scanning confocal microscope.
Results:OVA challenge induced an elevation of[Ca~(2+)]_i and an increase of NO,·OH and O_2·~- in sensitized rat macrophages,which were inhibited by ketamine.
Conclusions:Ketamine inhibited OVA-induced oxidative stress which involved in calcium.
目的:研究氯胺酮对脂多糖(LPS)刺激的大鼠肺泡巨噬细胞一氧化氮(NO)、羟自由基(·OH)、超氧阴离子(O_2·~-)生成及胞内游离钙离子([Ca~(2+)]_i)的影响。
方法:体外培养的大鼠肺泡巨噬细胞系NR8383分为对照组(C组),LPS组(L组)及不同浓度氯胺酮预处理组(K1、K2和K3组)。L组、K1、K2和K3组均采用1 mg/L的LPS刺激,在刺激前分别给以磷酸盐缓冲溶液(PBS)、10、100和1000 gmol/L浓度氯胺酮预处理。C组用相同剂量的PBS处理。继续培养24小时后用试剂盒检测细胞培养上清液中NO、·OH及(超氧阴离子)O_2·~-水平,应用激光共聚焦法测定胞内游离钙离子的水平。
结果:L组NO、·OH、O_2·~-及胞内游离钙离子的水平显著高于C组;与L组相比,K2和K3组的NO、·OH、O_2·~-及胞内游离钙离子的水平显著降低;K2和K3组间无统计学差异。
结论:氯胺酮(100和1000μmol/L)对LPS所致的NR8383的NO、·OH、O_2·~-及胞内游离钙离子的的升高有抑制作用。
第二部分氯胺酮对卵蛋白激发的致敏大鼠离体肺泡巨噬细胞胞内钙和自由基的影响
目的:研究氯胺酮对OVA刺激的致敏大鼠肺泡巨噬细胞(AM)一氧化氮(NO)、羟自由基(·OH)、超氧阴离子(O_2·~-)生成及胞内游离钙离子([Ca~(2+)]_i)的影响。
方法:SD大鼠经皮下注射OVA致敏后行肺泡灌洗,分离纯化后得到体外培养的AM,经氯胺酮(10μM,100μm和1000μM)处理、OVA刺激后,测定细胞[ca~(2+)]_i并检测细胞培养上清液中一氧化氮(NO)、羟自由基(·OH)及O_2·~-水平。
结果:OVA刺激可引起致敏肺泡巨噬细胞[Ca~(2+)]_i增高及NO、·OH和O_2·~-的生成增多,氯胺酮对此具有抑制作用。
结论:氯胺酮可抑制OVA所致的氧化应激,其分子机制可能与[Ca~(2+)]_i相关。
Part One
Effects of ketamine on nitrogen monoxidum,oxygen Radicals and free intracellular calcium in Lipopolysaccharide-stimulated rat alveolar macrophage in vitro
Objective:To investigate the effects of ketamine on production of Nitric oxide(NO),hydroxy radical(·OH),superoxide anion(O_2·~-)and free intracellular calcium([Ca~(2+)]_i)in the rat alveolar macrophage cell line (NR8383)activated by Lipopolysaccharide(LPS).
Methods:Macrophage was distributed into five groups,group C, group L,group K1,group K2 and group K3.Group L,K1,K2 and K3 were stimulated with LPS.Before stimulation,Group L,K1,K2 and K3 were treated with phosphate buffer solution(PBS),10,100and 1000μmol/L ketamine.Group C was treated with PBS.The levels of NO,·OH and O_2·~- in the supernatant were assayed.The[Ca~(2+)]i level was measured with fluorescent intensity by laser scanning confocal microscope.
Results:The concentrations of NO,·OH,O_2·~-and[Ca~(2+)]_i in group L increased significantly(P＜0.01)when compared to Group C.The concentrations of NO,·OH and O_2·~- in Group K2,K3 were obviously lower than those of Group L(P＜0.05).There was no statistical difference between K2 and K3(P＞0.05).
Conclusions:Ketamine(100 and 1000μmol/L)can inhibit LPS-induced production of NO,·OH,O_2·~- and[Ca~(2+)]_i.
Part Two
Effects of Ketamine on OVA-induced the changes of Free Intracellular Calcium and Free-radical in Alveolar Macrophages in Vitro
Objective:To observe the effect of ketamine on OVA-induced the changes of free intracellular calcium([Ca~(2+)]_i)and free-radical in alveolar macrophages from sensitized rat in vitro.
Methods:Macrophages were collected from Bronchoalveolar Lavage fluid of OVA-sensitized Sprague-Damley rats and treated with ketamine of concentration at 10μM,100μM and 1000μM before challenge with 100μg/mL OVA.The production of nitric oxide(NO),hydroxy radical (·OH)and superoxide anion(O_2·~-)in the supematant of culture was assayed by kits and the[Ca~(2+)]_i of macrophages was measured with mean fluorescent intensity(MFI)by laser scanning confocal microscope.
Results:OVA challenge induced an elevation of[Ca~(2+)]_i and an increase of NO,·OH and O_2·~- in sensitized rat macrophages,which were inhibited by ketamine.
Conclusions:Ketamine inhibited OVA-induced oxidative stress which involved in calcium.
引文
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