Everall I P, Trillo-Pazos G, Bell C, Mallory M, Sanders V, Masliah E
Institute of Psychiatry, DeCrespigny Park, London, United Kingdom.
J Neuropathol Exp Neurol. 2001 Mar;60(3):293-301. doi: 10.1093/jnen/60.3.293.
Approximately two thirds of patients with human immunodeficiency virus encephalitis (HIVE) show cognitive impairment and neurodegeneration, while one third are cognitively unimpaired and their neuronal populations are preserved. Thus, it is possible that these individuals might have the capacity to produce neurotrophic factors capable of protecting neurons against the deleterious effects of HIV. In this context, the main objective of this study was to determine whether fibroblast growth factor 1 (FGF1) is protective against HIV. For this purpose levels of FGF1 immunoreactivity were determined in the frontal cortex of 35 AIDS cases subdivided into 4 groups according to the presence or absence of HIVE and neurodegeneration. In cases without both HIVE and neurodegeneration, mild to moderate levels of FGFI immunoreactivity were observed in pyramidal neurons, while in cases with HIVE but without neurodegeneration, levels were significiantly elevated. In contrast, individuals with both HIVE and neurodegeneration showed low levels of neuronal FGF1 immunoreactivity. Furthermore, studies in primary human neuronal cultures treated with the HIV envelope protein-gp120 in the presence or absence of FGF1 showed that FGF1 was protective against gpl20 neurotoxicity in a dose-dependent manner. Taken together, these results support the notion that upregulation of certain neurotrophic factors, such as FGF1, might protect the central nervous system from the neurotoxic effects of HIV.
大约三分之二的人类免疫缺陷病毒脑炎（HIVE）患者表现出认知障碍和神经退行性变，而三分之一的患者认知功能未受损且其神经元群体得以保留。因此，这些个体有可能具备产生能够保护神经元免受HIV有害影响的神经营养因子的能力。在此背景下，本研究的主要目的是确定成纤维细胞生长因子1（FGF1）是否对HIV具有保护作用。为此，在35例艾滋病患者的额叶皮质中测定了FGF1免疫反应性水平，这些患者根据是否存在HIVE和神经退行性变被分为4组。在既无HIVE也无神经退行性变的病例中，在锥体细胞中观察到轻度至中度的FGF1免疫反应性水平，而在有HIVE但无神经退行性变的病例中，该水平显著升高。相比之下，同时患有HIVE和神经退行性变的个体神经元FGF1免疫反应性水平较低。此外，在有无FGF1存在的情况下用HIV包膜蛋白-gp120处理原代人神经元培养物的研究表明，FGF1以剂量依赖的方式对gp120神经毒性具有保护作用。综上所述，这些结果支持这样一种观点，即某些神经营养因子如FGF1的上调可能保护中枢神经系统免受HIV的神经毒性作用。
