Nicholl I D, Stitt A W, Moore J E, Ritchie A J, Archer D B, Bucala R
Picower Institute for Medical Research, Manhasset, New York 11030, USA.
Mol Med. 1998 Sep;4(9):594-601.
Advanced glycation endproducts (AGEs) arise from the spontaneous reaction of reducing sugars with the amino groups of macromolecules. AGEs accumulate in tissue as a consequence of diabetes and aging and have been causally implicated in the pathogenesis of several of the end-organ complications of diabetes and aging, including cataract, atherosclerosis, and renal insufficiency. It has been recently proposed that components in mainstream cigarette smoke can react with plasma and extracellular matrix proteins to form covalent adducts with many of the properties of AGEs. We wished to ascertain whether AGEs or immunochemically related molecules are present at higher levels in the tissues of smokers.
Lens and coronary artery specimens from nondiabetic smokers and nondiabetic nonsmokers were examined by immunohistochemistry, immunoelectron microscopy, and ELISA employing several distinct anti-AGE antibodies. In addition, lenticular extracts were tested for AGE-associated fluorescence by fluorescence spectroscopy.
Immunoreactive AGEs were present at significantly higher levels in the lenses and lenticular extracts of nondiabetic smokers (p < 0.003). Anti-AGE immunogold staining was diffusely distributed throughout lens fiber cells. AGE-associated fluorescence was significantly increased in the lenticular extracts of nondiabetic smokers (p = 0.005). AGE-immunoreactivity was significantly elevated in coronary arteries from nondiabetic smokers compared with nondiabetic nonsmokers (p = 0.015).
AGEs or immunochemically related molecules are present at higher levels in the tissues of smokers than in nonsmokers, irrespective of diabetes. In view of previous reports implicating AGEs in a causal association with numerous pathologies, these findings have significant ramifications for understanding the etiopathology of diseases associated with smoking, the single greatest preventable cause of morbidity and mortality in the United States.
晚期糖基化终末产物（AGEs）由还原糖与大分子的氨基自发反应产生。由于糖尿病和衰老，AGEs在组织中积累，并被认为与糖尿病和衰老的几种终末器官并发症的发病机制有关，包括白内障、动脉粥样硬化和肾功能不全。最近有人提出，主流香烟烟雾中的成分可与血浆和细胞外基质蛋白反应，形成具有许多AGEs特性的共价加合物。我们希望确定吸烟者组织中AGEs或免疫化学相关分子的水平是否更高。
采用几种不同的抗AGE抗体，通过免疫组织化学、免疫电子显微镜和酶联免疫吸附测定法（ELISA）对非糖尿病吸烟者和非糖尿病非吸烟者的晶状体和冠状动脉标本进行检测。此外，通过荧光光谱法检测晶状体提取物中的AGE相关荧光。
非糖尿病吸烟者晶状体和晶状体提取物中的免疫反应性AGEs水平显著更高（p < 0.003）。抗AGE免疫金染色弥漫分布于整个晶状体纤维细胞。非糖尿病吸烟者晶状体提取物中的AGE相关荧光显著增加（p = 0.005）。与非糖尿病非吸烟者相比，非糖尿病吸烟者冠状动脉中的AGE免疫反应性显著升高（p = 0.015）。
无论是否患有糖尿病，吸烟者组织中AGEs或免疫化学相关分子的水平均高于非吸烟者。鉴于先前有报道表明AGEs与多种疾病存在因果关系，这些发现对于理解与吸烟相关疾病的病因病理学具有重要意义，吸烟是美国发病率和死亡率的单一最大可预防原因。
