文章摘要
顾 昊,沈 伟,孙圣刚.美满霉素抑制脂多糖诱导的小胶质细胞诱导型一氧化氮合酶的表达及其相关机制[J].南京医科大学学报,2012,(2):188~193
美满霉素抑制脂多糖诱导的小胶质细胞诱导型一氧化氮合酶的表达及其相关机制
Inhibitory role of minocycline on lipopolysaccharide-induced iNOS expression in microglial cells and its underling mechanisms
投稿时间:2011-10-14  
DOI:10.7655
中文关键词: 美满霉素  脂多糖  小胶质细胞  一氧化氮  诱导型一氧化氮合酶  p38丝裂原活化蛋白激酶
英文关键词: minocycline  microglia  lipopolysaccharide  nitric oxide  iNOS  p38MAPK
基金项目:南京医科大学科技发展基金项目(07NJMUM033)
作者单位
顾 昊 南京医科大学附属脑科医院神经内科,江苏 南京 210029 
沈 伟 南京医科大学附属脑科医院神经内科,江苏 南京 210029 
孙圣刚 华中科技大学附属协和医院神经内科,湖北 武汉 430074 
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中文摘要:
      目的:探讨美满霉素(minocycline,MC)对脂多糖(lipopolysaccharide,LPS)诱导的小胶质细胞一氧化氮(NO)生成和诱导型一氧化氮合酶(iNOS)表达的影响及其相关分子机制?方法:LPS或联合MC刺激BV-2细胞,酶联免疫法检测培养上清中NO水平,免疫细胞化学观察iNOS的蛋白含量,RT-PCR技术评价iNOS的mRNA表达,免疫印迹研究p38丝裂原活化蛋白激酶(p38MAPK)的蛋白水平和磷酸化变化?结果:LPS(100 ng/ml)组NO含量显著升高(P < 0.05),且伴随iNOS蛋白和mRNA水平的明显上调,与对照组相比有显著性差异(P < 0.01)?MC(10 μmol/L)预处理(MC+LPS组)能明显抑制上述变化,NO含量?iNOS蛋白和mRNA水平较LPS组均显著下调(P均 < 0.01),但明显高于对照组(P均 < 0.05)?LPS也能诱导p38MAPK磷酸化,与对照组相比差异显著(P < 0.01),而MC预处理(MC+LPS组)能拮抗p38MAPK的磷酸化,较LPS组显著下调(P < 0.01),同时实验各组p38MAPK蛋白水平保持基本一致?结论:美满霉素能通过下调p38MAPK信号途径,抑制脂多糖刺激的小胶质细胞iNOS基因表达及NO生成,对脂多糖诱导的小胶细胞损伤有明显保护作用?
英文摘要:
      Objective: To explore the inhibitory effect of minocycline (MC) on lipopolysaccharide-induced production of nitric oxide(NO) and expression of induced nitricoxide synthase(iNOS) in BV-2 microglial cells and its molecular mechanisms. Methods: The BV-2 microglial cells were treated with LPS (100 ng/ml) or various concentrations of minocycline (0,0.1,1,10,100 μmol/L). Accumulated NO was measured in the cell supernatant by enzyme method,iNOS protein and mRNA were examined by immunochemistry staining and RT-PCR technique,respectively. p38MAPK protein was examined by Western blot in BV-2 cells. Results: The NO production and iNOS protein and mRNA levels were significantly increased in LPS group than those of the control group(P < 0.05, 0.01,0.01,respectively). The pre-treatment of MC(10 μmol/L) significantly inhibited the NO production and the increments of iNOS protein and mRNA induced by LPS. The NO contents and the levels of iNOS protein and mRNA in MC+LPS group were significantly lower than those of the LPS groups (all P < 0.01),but still significantly higher than those of the control group (all P < 0.05). There was not significant differences of total p38MAPK protein expression in all groups,but no phospho-p38MAPK proteins were detected in the control group and MC group. The level of phospho-p38MAPK in the control group was significantly lower than that of the LPS group (P < 0.01),in which the increased phospho-p38MAPK level was reversed by MC (P < 0.01),Conclusion: The pre-treatment of MC could significantly inhibit the NO production and the increase of iNOS protein and mRNA induced by LPS through inhibiting the p38MAPK pathway in microglial cell.
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