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硒及维生素E抑制补体-中性粒细胞活化反馈机制参与炎症应答的调控

Modulation of the Inflammatory Response through Complement- neutrophilActivation Feedback Mechanism with Selenium and Vitamin E

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【作者】 侯健存吴元德凌允礼

【Author】 Hou Jiancun Wu Yuande Ling Yunli (Department of Pathology, Institute of Basic Medical Sciences, CAMS and PUMC, Beijing 100005, China)

【机构】 中国医学科学院中国协和医科大学基础医学研究所病理室!北京100005

【摘要】 笔者发现并验证补体介导炎症损伤的机制是补体活化激活中性粒细胞( PMN)呼吸爆发所释放的活性氧自由基( ROS)能再次活化补体,在补体- PMN- ROS之间形成的这一相互反馈活化、增强炎症应答的辅助机制有其特殊的参与调节炎症应答的作用,即补体活化的抑制或 ROS的清除皆能阻滞此活化反馈机制而下调炎症应答。为验证此设想,笔者选择补体活化抑制剂亚硒酸钠( SS)、抗氧化剂维生素 E( VitE)与甘草类黄酮( GF)抑制补体- PMN- ROS活化反馈机制,在试管实验中利用化学发光技术,在 PMN及补体混合培养液中以佛波酯( TPA)或菊糖单独活化 PMN或补体后检测活性氧的产生量及补体的活化程度;并在小鼠体内实验中观察肺、肝及皮肤血管炎模型的发生率。结果证实此活化反馈上调炎症应答机制的存在;补体活化的抑制或 ROS的清除皆能抑制上调炎症应答,防止血管炎的发生,其发生率可从不服药组的 100%降至各剂量服药组的 20%~ 57%。本研究不但为阐明炎症反应的发生和调控机制提供了新的证据,而且进一步提示 PMN呼吸爆发产生 ROS是炎症反应组织损伤的生理及病理过程中的关键,因此有可能使用营养素抗氧化剂( nutrient antioxidants)来调节生物炎症反应。以往在一次流行性出血热疫区选择 80例患者仅以亚?

【Abstract】 To identify the regulatory effect of sodium selenite and vitamin E on the complement- neutrophil- reactive oxygen(ROS) activation feedback( CNAF) mechanism mediated inflammatory response, we detected ROS production and complement activation in vitro tests by chemiluminescence technique and complement fixation and recognized the regulation of the inflammatory response in vivo mouse vasculitis models of skin,lung,and liver. Convincing results were observed as both in vitro and in vivo experiments showing inhibition of CNAF mechanism with sodium selenite and vitamin E could effect the reduced ROS production and complement activation .The incidence (100% )for vasculitis in control group decreased to 20%~ 57% in sodium selenite and vitamin E treated groups. Elucidation of the ancillary mechanism of CNAF enhancing inflammatory response is a promising area for new therapeutic developments in the modulation of inflammatory response. As in a clinical approach, a remarkable therapeutic effect with sodium selenite was observed during an epidemic episode of epidemic hemorrhagic fever in Henan province .The mortality rate of fulminant cases was reduced from 100% of untreated control cases to 36.6% by treatment with sodium selenite. The results of present studies strongly suggest that antioxidants such as selenium and vitamin E as well as others like flavonoids can exhibit a novel anti- inflammatory action via this CNAF mechanism.It is expected in the future an increasing number of patients with severe infections or inflammatory disorders in which excessive complement activation and adverse ROS production have been implicated, e.g. ischemia- reperfusion injury, severe sepsis and diverse inflammatory vascular injuries like rheumatoid arthritis, hepatitis and inflammatory bowel diseases should benefit from this newer concept guided adjuvant therapies which make use of nutrient antioxidants like selenium,vitamin E and others.

【基金】 国家自然科学基金!( 39670288);卫生部科学研究基金!( 88101002)
  • 【文献出处】 中国医学科学院学报 ,Acta Academiae Medicinae Sinicae , 编辑部邮箱 ,2000年06期
  • 【分类号】R392.11
  • 【被引频次】7
  • 【下载频次】157
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