可 溶性高级化糖基化终末产物受体sRAGE可以结合高级糖基化终末产物（AGE），是反映二型糖尿病或代谢综合征微血管损伤一个可靠的生物标示物，与 IMT(intima-media-thickness)有显著的正相关关系。可溶性高级化糖基化终末产物受体在体内存在一种变异型缺乏转膜区结构，它可 以分泌到血液中， 称之为内源性分泌型高级化糖基化终末产物受体esRAGE。目前研究资料表明，可溶性高级化糖基化终末产物受体sRAGE含量较高，是内源性分泌型糖基化 高级化终末产物受体esRAGE的5~10倍高。可溶性高级化糖基化终末产物受体sRAGE和IMT相关。而esRAGE只和年龄相关。爱迪博生物的研究 人员关注于研究可溶性高级化糖基化终末产物受体sRAGE在代谢综合征中的生物学意义，它在急性冠状动脉综合征伴有血管损伤的临床检测意义值得关注。研究 资料显示，血清或血浆中的sRAGE在慢性肾脏疾病、冠心病、二型糖尿病、肥胖等呈现下降趋势， 并且与BMI、CRP、甘油三酯、低密度脂蛋白呈现负相关关系。与高密度脂蛋白、脂联素等呈现正相关关系。提示， sRAGE是机体内的一种保护性细胞因子。
| RAGE and cellular stress: initiating factor and/or amplifier of inflammatory mechanisms and tissue injury? In the multiple hit model, certain disease states are characterized by basally enhanced generation of RAGE ligands (AGEs, S100/calgranulins, amphoterin, and/or Mac-1), in parallel with increased expression of RAGE (hit one). On superimposed stresses (hit two), such as infection, renal failure, hyperglycemia, physical stress, hyperlipidemia, aging, or autoimmunity, further generation of RAGE ligands activates signal transduction mechanisms, via RAGE, that lead to upregulation of inflammatory and prothrombotic pathways. If left unchecked, these processes amplify inflammation and tissue destruction. In the alternate view, basal upregulation of the ligand–RAGE axis itself, as a single hit, contributes innately to the development of vascular inflammation and tissue injury. Experiments must be performed to dissect the contribution of each facet of the RAGE axis in vascular and other forms of inflammatory disorders. |
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Model for the potential sources of sRAGE. There are a number of potential means by which sRAGE may be generated. First, it is possible that yet to be delineated mechanisms may cleave sRAGE from the endogenous full-length cell surface receptor. Second, multiple discrete novel splice variants of RAGE may generate diverse sRAGEs. The assay used by Falcone and colleagues in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology does not distinguish these possibilities. Although this cartoon suggests that endothelial cells may be a principal source of sRAGE, it is possible that other cells such as smooth muscle cells or circulating inflammatory cells may generate sRAGEs. Key roles for sRAGEs, as decoys for the cell surface receptor RAGE, may serve as biomarker and/or endogenous protection factor in diseases characterized by upregulation of RAGE ligands.
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