晚期糖基化终末产物在糖尿病大鼠骨质疏松发病中的作用及胰岛素潜在的防护机制

目的探讨循环中晚期糖基化终末产物（advanced glycation end products，AGEs）在糖尿病大鼠骨质疏松发病中的作用及胰岛素潜在的防护机制。方法将3月龄雄性SD大鼠用链脲佐菌素（streptozotocin STZ）诱导成速发型糖尿病大鼠模型，随机分为胰岛素治疗组（n=10）和模型组（n=10）并以正常大鼠作对照组（n=10）。20周后下腔静脉采血处死大鼠,用Hitachi-850型荧光分光光度计测定血清中AGEs含量的变化，取一侧股骨和胫骨行X线拍片和骨密度测量,对侧胫骨近端制作病理标本，股骨行RT-PCR测定RAGE的含量。结果20周后，模型组与对照组相比，骨质疏松明显，股骨BMD、血清中AGEs、骨组织中RAGE的表达与对照组比均有统计学意义(P＜0．01)。胰岛素治疗组与模型组相比，股骨BMD明显升高 (P＜0．01)，血清中AGEs减少(P＜0．01)，骨组织中晚期糖基化终末产物受体(receptor for advanced glycation end products, RAGE)的表达下降。结论骨组织中AGEs和RAGE相互作用是糖尿病骨质疏松的重要致病机制之一，胰岛素对糖尿病大鼠骨质疏松具有防护作用，其作用机制可能与严格控制血糖、抑制AGEs的合成、阻断骨组织中AGEs和RAGE相互作用有关，从而提高大鼠骨密度，改善骨质量。

AGEs in the pathogenesis of diabetic osteoporosis and the preventive mechanism of insulin

Objective To explore the role of AGEs in the pathogenesis of diabetic osteoporosis and the preventive effect of insulin on diabetic osteoporosis in streptozotocin(STZ)-diabetic rats.Methods Thirty male Sprague-Dawley(SD) rats were randomly divided into the control(C,n=10) and the STZ-induced diabetic groups(n=20),and then the diabetic rats were randomly divided into another two groups: the insulin group(n=10) that was treated with enough insulin to strictly control the high concentration of blood glucose,and the DM group(n=10) in which high blood glucose was not controlled.20 weeks later the animals were sacrificed by exsanguination.The serum levels of advanced glycosylation end products(AGEs) concentration were determined by fluorescence spectrophotometry.Distracted tibiae and femora were analyzed by radiography and by DEXA.The contra-lateral tibiae were histologically analyzed.The presence of the receptor for advanced glycosylation end products(RAGE) in the femora was determined by immunohistochemistry and RT-PCR.Results After 20 weeks,compared with the control group,the DM group demonstrated an obvious osteoporosis,the bone mineral density(BMD)values of the femora was significantly decreased,while the serum levels of AGEs were significantly increased(P<0.01).The expression level of RAGE in the DM group was markedly increased comparedwith the control group(P<0.01).Compared with the DM group,the control group did not demonstrated obvious osteoporosis,the BMD value of the femora was significantly increased and the serum level of AGEs was significantly decreased(P<0.01).The expression level of RAGE in the insulin group was markedly increased compared with the DM group(P<0.01).Conclusions Interaction between AGEs and RAGE has an important role in osteoporosis and administration of insulin has a preventive effect on osteoporosis in STZ-diabetic rats in vivo.The effects of insulin may be associated with the possible mechanism of lowering the high glucose,inhibiting AGEs synthesis and blocking the interaction between AGEs and RAGE.