阵发性睡眠性血红蛋白尿症（PNH）病态红细胞的研究
摘要
阵发性睡眠性血红蛋白尿症(PNH)是一种原因不明的后天获得的血细胞膜缺陷病。对其溶血机制的研究一直是国际上众多学者的重要课题。虽然体外试验已证明PNH红细胞对补体敏感，但迄今仍无充分证据说明体内每例患者的每次溶血发作都属补体溶血。现已得知PNH的分子病理学基础是PNH红细胞膜有内在缺陷，对补体敏感只是这种缺陷的外在表现之一。全面了解PNH病态红细胞的膜缺陷，及其对红细胞的影响，是阐明溶血机制的关键环节之一。过去研究中的另一障碍是患者体内同时存在病态的和“正常”的红细胞类群，不同患者，不同时间各细胞类群的比例还可有差别。这使得观察的结果只能反映PNH混合红细胞群的情况，不能确切代表病态红细胞的本质。本研究针对上述两方面的问题，先设法将PNH红细胞分离纯化成具有不同特征的类群，然后对之进行多方面的观察，所得结果如下：
用单克隆抗体——亲和层析方法分离得到缺乏乙酰胆碱脂酶[AchE(-)]的PNH红细胞，这是PNH红细胞中有代表性的膜上缺乏PI-连接蛋白病态细胞。我们观察发现这类细胞对补体溶血敏感，但与膜上缺乏C_3转化酶衰变加速因子[DAF(-)]PNH红细胞比，后者对补体更敏感。同时还发现这两个PI-连接蛋白(AchE和DAF)从PNH红细胞膜上丢失可不同步。AchE(-)PNH红细胞的变形性很差，这类细胞易于自发产生超
Paroxysmal nocturnal hemoglobinuria ( PNH) is an acquired hemolytic disorder commonly seen in North China. The foundamental nature of the disease is still not well defined and many questions as to mechanism of hemolysis remain unanswered. One of the main obstacles in study is the intermingling of different red cell populations in patients' peripheral blood. In the present investigation, we tried to explore the abnormalities of PNH erythocytes ( PNHE) , which were separated into different categories. Our purpose is to identify the defects of PNHE belonging to different categories and to elucidate their individual abnormalities which may lead to hemolysis. The
用单克隆抗体——亲和层析方法分离得到缺乏乙酰胆碱脂酶[AchE(-)]的PNH红细胞，这是PNH红细胞中有代表性的膜上缺乏PI-连接蛋白病态细胞。我们观察发现这类细胞对补体溶血敏感，但与膜上缺乏C_3转化酶衰变加速因子[DAF(-)]PNH红细胞比，后者对补体更敏感。同时还发现这两个PI-连接蛋白(AchE和DAF)从PNH红细胞膜上丢失可不同步。AchE(-)PNH红细胞的变形性很差，这类细胞易于自发产生超
Paroxysmal nocturnal hemoglobinuria ( PNH) is an acquired hemolytic disorder commonly seen in North China. The foundamental nature of the disease is still not well defined and many questions as to mechanism of hemolysis remain unanswered. One of the main obstacles in study is the intermingling of different red cell populations in patients' peripheral blood. In the present investigation, we tried to explore the abnormalities of PNH erythocytes ( PNHE) , which were separated into different categories. Our purpose is to identify the defects of PNHE belonging to different categories and to elucidate their individual abnormalities which may lead to hemolysis. The
引文
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4．不同类群PNHE膜上的SDS-PAGE电泳图谱与正常人E无明显差异．
5．PNHE自发产生活性氧多，抗氧化酶活性减低．氧化损伤的表现比正常E多，不论E膜缺失AchE与否均如此，PNH容易遭受氧化损伤现象与膜上PI-连接蛋白(至少是AchE)可能无关．
6．活性氧对PNHE损伤作用，是PNHE溶破机制中一个不可忽略的环节．
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4．不同类群PNHE膜上的SDS-PAGE电泳图谱与正常人E无明显差异．
5．PNHE自发产生活性氧多，抗氧化酶活性减低．氧化损伤的表现比正常E多，不论E膜缺失AchE与否均如此，PNH容易遭受氧化损伤现象与膜上PI-连接蛋白(至少是AchE)可能无关．
6．活性氧对PNHE损伤作用，是PNHE溶破机制中一个不可忽略的环节．
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