The Relationship Between Advanced Glycation End Products And Healing Of Diabetic Foot Ulcers

BackgroundThe formation of advanced glycation end products (AGEs) is a process described as non-enzymatic glycation involves the condensation reaction of some reducing sugar such as glucose and fructose with the N-terminus or free-amino groups of proteins in vivo.At first they form a Schiff base, and then the labile adduct undergoes rearrangements to the more stable Amadori-products, for example hemoglobinA1c. Amadori-products are in equilibrium with glucose and, therefore, the levels of Amadori-products will tend to rise and fall depending on the glucose concentration in plasma. That is to say, they can be disocciated when the glucose concentration is lower. However, if it keeps rising, the Amadori-products undergo further dehydrogenation,oxidative reaction, cross-linking reaction and can give rise to irreversibly formed AGEs. In recent years,some study demonstrated that AGEs were related to the nerve dysfunction, microvascular and/or macrovascular disease and impaired wound healing.As we know,fibroblasts play an important role in the wound healing process. They can secrete plenty of collagen fibers and matrix components, which constitute granulation tissue with neocapillaries together and fill tissue defect, as a result, it makes more convenient for covering with epidermal cells. Changes in the shape and quantity of fibroblast can directly influence the wound healing.ObjectiveTo investigate the content of advanced glycation end products(AGEs)in the patients'skin with diabetic foot ulcers and to observe the effect of advanced glycation end products(AGEs) on the morphological character and proliferation of fibroblast(Fb), and thus to enrich the mechanism in impaired wound healing of diabetic foot ulcers and to provide theoretical basis for the treatment of diabetic foot ulcers.Methods1. collecting skin specimens from diabetic and non-diabetic patients and the specimens from the former would be taken in local lesion and relatively normal tissue respectively and then detecting the content of AGEs by immunohistochemistry assay.2. Fb was cultured in vitro, exposing to a certain concentration of AGEs for 48 hours, and observe the morphologic alteration at high magnification.3. Fb was cultured in vitro, exposing to different concentrations of AGEs for 48 hours, and examine the proliferation of Fb by MTT colorimetry.Results1. There were more AGEs accumulated in diabetic patients compared with controls and in diabetic group, the expression of AGEs was higher in local lesion.2. The nomal fibroblasts have a couple of long lamellipodia. In contrast, Fbs with a certain concentration of AGEs had less and shorter lamellipodia.3. The quantity of Fbs with different concentrations of AGEs was significantly decreased(P<0.01) within tested dose range in a dose dependent pattern. Conclusions1. The diabetic skin had higher expression of AGEs, expecially in local lesion.2. AGEs could alter the shape and inhibit the proliferation of Fb obviously.It may partly account for the delayed healing of diabtic foot ulcers.