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.doc

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 【关键词】 糖尿病大鼠 骨质疏松 胰岛素 骨密度 晚期糖基化终末产物 晚期糖基化终末产物受体 ZHANG Lei， LI Mu， QI Lei， CAI Zhongxu， LI Yuhua, SUN Yuanliang （Department of Orthopedics, Qilu Hospital of Shandong University, Jinan 250012, China） Abstract: 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 compared with 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 Inte