Kalousová Marta, Zima Tomás, Tesar Vladimír, Dusilová-Sulková Sylvie, Skrha Jan
Institute of Clinical Chemistry and Laboratory Diagnostics, First Faculty of Medicine and General University Hospital, Charles University, Katerinská 32, 12108 Prague 2, Czech Republic.
Mutat Res. 2005 Nov 11;579(1-2):37-46. doi: 10.1016/j.mrfmmm.2005.03.024. Epub 2005 Aug 5.
Several diseases (atherosclerosis, diabetes mellitus, chronic renal failure) are associated with oxidative and carbonyl stress, microinflammation and eventually autoimmune reaction. Both oxidative and carbonyl stress cause damage to important biological structures-proteins, carbohydrates, lipids and nucleic acids and may enhance inflammatory response. New compounds and modified structures are formed, among them advanced oxidation protein products (AOPP), advanced glycation end products (AGEs-e.g. pentosidine, carboxymethyllysine) and advanced lipoperoxidation end products (ALEs). Accumulation of glycoxidation products, upregulation of protective mechanisms like glyoxalase I as well as enhanced transcription of genes coding for cytokines, growth factors and adhesive molecules via AGE-RAGE (receptor for AGEs) interaction and subsequent increase of classical acute phase reactants (e.g. CRP-C-reactive protein or orosomucoid) can be observed in a variety of chronic diseases. Additionally, several RAGE gene polymorphisms have shown association with some pathological states-diabetic complications, vascular damage, inflammatory response or antioxidant status. Recent advances in understanding the pathogenesis of chronic diseases provide new possibilities for diagnostics and monitoring of severely ill patients, however, further studies are still required to establish efficient therapeutical strategies.
几种疾病（动脉粥样硬化、糖尿病、慢性肾衰竭）与氧化应激和羰基应激、微炎症以及最终的自身免疫反应相关。氧化应激和羰基应激都会对重要的生物结构——蛋白质、碳水化合物、脂质和核酸造成损害，并可能增强炎症反应。会形成新的化合物和修饰结构，其中包括晚期氧化蛋白产物（AOPP）、晚期糖基化终产物（如戊糖苷、羧甲基赖氨酸等AGEs）和晚期脂质过氧化终产物（ALE）。在多种慢性疾病中都可观察到糖氧化产物的积累、乙二醛酶I等保护机制的上调，以及通过AGE-RAGE（AGEs受体）相互作用导致的细胞因子、生长因子和黏附分子编码基因的转录增强，随后经典急性期反应物（如CRP-C反应蛋白或血清类黏蛋白）增加。此外，几种RAGE基因多态性已显示与某些病理状态——糖尿病并发症、血管损伤、炎症反应或抗氧化状态相关。在理解慢性疾病发病机制方面的最新进展为重症患者的诊断和监测提供了新的可能性，然而，仍需要进一步研究来制定有效的治疗策略。
