Vincent V A, De Groot C J, Lucassen P J, Portegies P, Troost D, Tilders F J, Van Dam A M
Department of Pharmacology, Medical Faculty, Research Institute Neurosciences Free University, Amsterdam, The Netherlands.
AIDS. 1999 Feb 25;13(3):317-26. doi: 10.1097/00002030-199902250-00003.
To determine the occurrence and cellular localization of inducible nitric oxide synthase (iNOS), NOS activity and its association with cell death in brains of AIDS and AIDS dementia complex (ADC) patients.
Post-mortem cerebral cortex tissue of eight AIDS patients, eight ADC patients and eight control subjects was processed for iNOS immunocytochemistry, NADPH-diaphorase activity staining as an index of NOS activity, and in situ end-labelling to detect cell death.
iNOS-positive cells were present in the white matter of 14 out of 16 AIDS and ADC patients, whereas two out of eight control subjects showed iNOS-positive cells. iNOS immunoreactivity was exclusively localized in activated macrophages and microglial cells that both showed NADPH-diaphorase activity. In addition, NADPH-diaphorase activity, not related to iNOS immunoreactivity, was observed in astrocytes in both white and grey matter of AIDS and ADC patients. All AIDS and ADC patients, and only one control subject showed characteristic features of apoptotic cell death.
Different forms of NOS are present in microglial cells and astrocytes of AIDS and ADC patients but are largely absent in control subjects. Although more NOS-expressing cells occur in ADC than in AIDS patients, apoptotic cell death was found in both patient groups to the same extent. We postulate that NO production in brains of AIDS patients results in cumulative cortical cell loss, which becomes neurologically evident at later stages of disease and is expressed as ADC.
确定诱导型一氧化氮合酶（iNOS）在艾滋病（AIDS）和艾滋病痴呆综合征（ADC）患者大脑中的发生情况、细胞定位、一氧化氮合酶（NOS）活性及其与细胞死亡的关系。
对8例艾滋病患者、8例ADC患者和8例对照者的死后大脑皮质组织进行处理，用于iNOS免疫细胞化学检测、以NADPH - 黄递酶活性染色作为NOS活性指标以及原位末端标记以检测细胞死亡。
16例艾滋病和ADC患者中有14例的白质中存在iNOS阳性细胞，而8例对照者中有2例显示iNOS阳性细胞。iNOS免疫反应性仅定位于同时显示NADPH - 黄递酶活性的活化巨噬细胞和小胶质细胞中。此外，在艾滋病和ADC患者的白质和灰质中的星形胶质细胞中观察到与iNOS免疫反应性无关的NADPH - 黄递酶活性。所有艾滋病和ADC患者，只有1例对照者表现出凋亡细胞死亡的特征性表现。
不同形式的NOS存在于艾滋病和ADC患者的小胶质细胞和星形胶质细胞中，但在对照者中基本不存在。虽然ADC患者中表达NOS的细胞比艾滋病患者更多，但两个患者组中凋亡细胞死亡的程度相同。我们推测，艾滋病患者大脑中一氧化氮的产生导致皮质细胞逐渐丢失，在疾病后期神经学上变得明显，并表现为ADC。
