类风湿血液和膝关节滑液产生羟基自由基的情况。
Hydroxyl radical generation by rheumatoid blood and knee joint synovial fluid.
作者信息
Kaur H, Edmonds S E, Blake D R, Halliwell B
机构信息
International Antioxidant Research Centre, University of London, King's College, United Kingdom.
出版信息
Ann Rheum Dis. 1996 Dec;55(12):915-20. doi: 10.1136/ard.55.12.915.
OBJECTIVE
To demonstrate directly that highly reactive hydroxyl radicals (OH.) can be generated in patients with rheumatoid arthritis and contribute to joint damage, and to examine the ability of blood to cause OH. generation.
METHODS
The sensitive and specific technique of hydroxylation of aromatic compounds (salicylate and phenylalanine) was used to measure OH.. Synovial fluid and blood from patients with active rheumatoid arthritis were aspirated and immediately added to tubes containing salicylate and phenylalanine as detectors of OH., or to tubes containing saline as a control. Levels of specific products of attack of OH. upon salicylate (2,3- and 2,5-dihydroxybenzoates) and phenylalanine (ortho- and meta-tyrosines) were measured by high performance liquid chromatography.
RESULTS
Synovial fluid samples aspirated into saline never contained ortho- or meta-tyrosines or 2,3-dihydroxybenzoate. Of 53 patients examined, synovial fluid and blood from 36 caused formation of ortho- and meta-tyrosines when aspirated into solutions containing phenylalanine. Repeated sampling from three "positive" patients showed consistent evidence of these hydroxylation products. Similarly, of 22 patients examined, synovial fluid and blood from 18 caused formation of 2,3- and 2,5-dihydroxybenzoates when aspirated into salicylate solutions. Further evidence for the role of OH. was provided by inhibition of the hydroxylation by the specific OH. scavengers mannitol and sodium formate.
CONCLUSIONS
Aspirated knee joint fluids and blood from rheumatoid arthritis patients can generate OH., consistent with current views on the importance of this radical as a cytotoxic agent in rheumatoid disease. The ability of body fluids to cause OH. formation is not correlated with simple laboratory indices of disease activity, but is reproducible on sequential sampling from the same patients. The mechanism and significance of the phenomenon in rheumatoid arthritis pathology remain to be established.
目的
直接证明类风湿关节炎患者体内可产生高反应性的羟基自由基（OH·）并导致关节损伤，同时检测血液引发OH·生成的能力。
方法
采用芳香族化合物（水杨酸和苯丙氨酸）羟基化的灵敏且特异的技术来检测OH·。抽取活动性类风湿关节炎患者的滑液和血液，立即将其加入含有水杨酸和苯丙氨酸作为OH·检测剂的试管中，或加入含有生理盐水的试管作为对照。通过高效液相色谱法测定OH·攻击水杨酸（2,3 - 二羟基苯甲酸和2,5 - 二羟基苯甲酸）和苯丙氨酸（邻酪氨酸和间酪氨酸）的特定产物水平。
结果
抽取到生理盐水中的滑液样本从未含有邻酪氨酸或间酪氨酸或2,3 - 二羟基苯甲酸。在接受检查的53例患者中，当将滑液和血液抽取到含有苯丙氨酸的溶液中时，36例患者的样本导致了邻酪氨酸和间酪氨酸的形成。对3例“阳性”患者进行重复采样，显示出这些羟基化产物的一致证据。同样，在接受检查的22例患者中，当将滑液和血液抽取到含有水杨酸的溶液中时，18例患者的样本导致了2,3 - 二羟基苯甲酸和2,5 - 二羟基苯甲酸的形成。OH·特异性清除剂甘露醇和甲酸钠对羟基化的抑制作用进一步证明了OH·的作用。
结论
类风湿关节炎患者抽取的膝关节液和血液可产生OH·，这与当前关于该自由基作为类风湿疾病中细胞毒性因子重要性的观点一致。体液引发OH·形成的能力与疾病活动的简单实验室指标无关，但在对同一患者进行连续采样时具有可重复性。该现象在类风湿关节炎病理学中的机制和意义仍有待确定。
Zotero 插件