阵发性睡眠性血红蛋白尿症患者血小板膜补体复合物沉积及其异常活化的研究  

Study on C5b-9 deposited on the membrane of platelets and its dysfunction in patients with paroxysmal nocturnal hemoglobinuria

作　　者：孟银苹 付蓉[1] 刘惠[1] 王一浩[1] 李丽娟[1] 刘春燕[1] 张田[1] 丁少雪[1] 李丽燕[1] 阮二宝[1] 瞿文[1] 王化泉[1] 王晓明[1] 王国锦[1] 刘鸿[1] 吴玉红[1] 宋嘉[1] 邢莉民[1] 关晶[1] 邵宗鸿[1] 

机构地区：[1]天津医科大学总医院血液内科,300052

出　　处：《中华血液学杂志》2015年第6期515-519,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金（81370607、81400085）;天津市自然科学基金重点项目（12JCZDJC21500）;天津市卫生行业重点攻关项目（11KG135）;卫生公益性行业科研专项（201202017）;天津市自然科学基金面上项目（14JCYBJC25400）

摘　　要：目的 通过检测阵发性睡眠性血红蛋白尿症（PNH）伴或不伴再生障碍性贫血（AA）患者血小板膜补体复合物（C5b-9）、血小板活化分子（CD62p）表达及血清可溶性C5b-9（sC5b-9）水平探究PNH血栓形成的病理机制.方法 用ELISA方法检测25例PNH/PNH-AA患者血清sC5b-9、补体C3和C4水平,并以30名健康志愿者作为正常对照;采用流式细胞术检测PNH/PNH-AA患者与正常人血小板PNH克隆数（CD59-CD61＋/CD61＋）、血小板膜C5b-9沉积率（C5b-9＋CD61＋/CD61＋）以及血小板活化标志分子CD62p表达率（CD62p＋CD61＋/CD61＋）,并进行相关性分析.结果 ①PNH/PNH-AA组患者血清sC5b-9水平为390.27（265.73～676.87）μg/L,显著低于正常对照组的540.39（344.20～1 576.78）tg/L（P＜0.01）.②PNH/PNH-AA组患者血小板PNH克隆数[50.58（23.29～81.60）％]显著高于正常对照组[23.57（15.58～29.02）％]（P＜0.01）;PNH/PNH-AA组患者PNH克隆血小板膜C5b-9沉积率[（17.53±6.27）％]与患者正常血小板[（11.33±5.03）％]及正常对照组血小板[（10.88±3.58）％]相比均显著增高（P＜0.01）.③PNH/PNH-AA组患者PNH克隆血小板CD62p表达率[（61.98±11.71）％]与患者正常血小板[（43.76±11.30）％]及正常对照组血小板[（38.23±8.07）％]相比均显著升高（P＜0.01）;PNH/PNH-AA组患者正常血小板膜CD62p表达率比正常对照组血小板显著增高（P＜0.05）.④血小板膜C5b-9沉积率与CD62p表达率呈显著正相关（r=0.449,P=0.002）.结论 PNH/PNH-AA患者血小板锚连蛋白（CD59）缺失导致补体复合物C5b-9沉积于异常血小板膜并使其激活,这一过程可能参与PNH血栓的形成.Objective To explore the expression levels of terminal complement complex （C5b-9） and CD62p on platelets and the soluble C5b-9 （sC5b-9） level in serum in patients with PNH or PNH-aplastic anemia （AA）.Methods Serum levels ofsC5b-9,complement C3 and C4 were detected by using ELISA in 25 patients with PNH/PNH-AA.The quantities of C5b-9 and CD62p on the membrane of platelets were detected by flow cytometry.Results ①In PNH/PNH-AA group,the serum sC5b-9 level [390.27 （265.73-676.87） μg/L] was lower than that in control group [540.39 （344.20-1 576.78） tg/L] （P＜ 0.01）.②The platelet PNH clone （CD59-CD61VCD61＋） size [50.58 （23.29-81.60）％] was bigger in the PNH/PNH-AA group than that [23.57 （15.58-29.02）％] in control group （P＜0.01）.The percentages of C5b-9 deposition （C5b-9＋CD61＋/CD61＋） were higher on the PNH clone platelets （CD59-CD61＋） in the PNH/PNH-AA group [（17.53±6.27）％] than those on the normal platelets （CD59＋CD61＋） in PNH patients [（11.33±5.03）％] and control [（10.88±3.58）％] group （P＜0.01）.③The expression of CD62p （CD62p＋CD61 ＋/CD61 ＋） on PNH clone platelets in PNH patients [（61.98± 11.71）％] was higher than that on the normal platelets in PNH patients [（43.76±11.30）％] and control group [（38.23±18.07）％] （P＜0.01）.In addition,the expression of CD62p on normal platelets was higher in PNH patients than control （P＜0.05）.④The deposition of C5b-9 positively correlated with the expression of CD62p on the platelets （r=0.559,P=0.002）.Conclusions Deficiency of CD59 antigen on platelets in PNH patients may lead to the deposition of C5b-9 on its membrane and its dysfunction,which may contribute to thrombosis events in PNH.

关 键 词：血红蛋白尿 阵发性 补体膜攻击复合物 血栓形成 

分 类 号：R556.64[医药卫生—血液循环系统疾病]