Poli G, Parola M
Department of Experimental Medicine and Oncology, University of Torino, Italy.
Free Radic Biol Med. 1997;22(1-2):287-305. doi: 10.1016/s0891-5849(96)00327-9.
Various chronic disease processes are characterized by progressive accumulation of connective tissue under-going fibrotic degeneration. Evidence of oxidative reactions is often associated with fibrogenesis occurring in liver, lung, arteries, and nervous system. Moreover, an increasing bulk of experimental and clinical data supports a contributory role of oxidative stress in the pathogenesis of this kind of disease. Indeed, many etiological agents of fibrogenesis stimulate free radical reactions either directly or through inflammatory stimuli. Free radicals, as well as products of their reaction with biomolecules, appear to modulate the activity of the two cellular types mainly involved in the process, namely phagocytes and extracellular matrix-producing cells. Lipid peroxidation and certain lipid peroxidation products induce genetic overexpression of fibrogenic cytokines, the key molecules in the pathomechanisms of fibrosis, as well as increased transcription and synthesis of collagen. Both these events can be downregulated, at least in experimental models, by the use of antioxidants. The effect of oxidative stress on cytokine gene expression appears to be an important mechanism by which it promotes connective tissue deposition.
各种慢性疾病过程的特征是经历纤维化变性的结缔组织进行性积累。氧化反应的证据常与肝脏、肺、动脉和神经系统中发生的纤维生成有关。此外，越来越多的实验和临床数据支持氧化应激在这类疾病发病机制中的作用。实际上，许多纤维生成的病因学因素直接或通过炎症刺激来刺激自由基反应。自由基以及它们与生物分子反应的产物似乎调节了主要参与该过程的两种细胞类型的活性，即吞噬细胞和产生细胞外基质的细胞。脂质过氧化和某些脂质过氧化产物诱导促纤维化细胞因子的基因过度表达，这些细胞因子是纤维化发病机制中的关键分子，同时还会增加胶原蛋白的转录和合成。至少在实验模型中，使用抗氧化剂可下调这两个事件。氧化应激对细胞因子基因表达的影响似乎是其促进结缔组织沉积的重要机制。
