Li Yong, Shen Guang-Si, Yu Chen, Li Guang-Fei, Shen Jun-Kang, Xu You-Jia, Gong Jian-Ping
Department of Radiology, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
Department of Orthopaedics, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
Int J Clin Exp Pathol. 2015 Feb 1;8(2):1604-12. eCollection 2015.
This study was performed to investigate bone deteriorations and the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) of male rat in response to the hyperglycemia.
The biomarkers in serum and urine were measured by ELISA kit, and tibias were taken for the measurement on gene, protein expression and histological analysis, femurs were taken for the measurement on biomechanical parameters and micro-CT.
The DM1 showed the decreased level of osteocalcin, testosterone and FGF-23, and the increased level of serum CTX as compared to those of vehicle group. The H&E staining showed remarkable bone deteriorations, including increased disconnections and separation of trabecular bone among growth plate and joint cartilage in DM1 group. Biomechanically, the maximum load, maximum stress, and strain parameter of DM1 group was significantly lower than control group. Type 1 diabetic mice displayed bone loss shown the reduction of bone volume/total volume, trabecular number, trabecular thickness and bone mineral density. The STZ injection significantly up-regulated mRNA expression of AT1R, AGT, renin, renin-receptor, and ACE, and the expression of AT2R, B1R and B2R were down-regulated in tibia of rat in hyperglycemia group. The protein expression of renin, ACE and Ang II were significantly up-regulated, and AT2R, B1R and B2R were down-regulated in DM1 group.
The treatment of hyperglycemia was detrimental to bone as compared to the vehicle group, and the underlying mechanism was mediated, at least partially, through down-regulation of KSS activity and up-regulation of RAS activity in local bone.
本研究旨在探讨雄性大鼠在高血糖状态下的骨质恶化情况以及骨骼肾素-血管紧张素系统（RAS）和激肽释放酶-激肽系统（KKS）的参与情况。
采用酶联免疫吸附测定（ELISA）试剂盒检测血清和尿液中的生物标志物，并取胫骨进行基因、蛋白质表达及组织学分析，取股骨进行生物力学参数测定和显微计算机断层扫描（micro-CT）。
与对照组相比，1型糖尿病（DM1）组骨钙素、睾酮和FGF-23水平降低，血清I型胶原交联C端肽（CTX）水平升高。苏木精-伊红（H&E）染色显示骨质明显恶化，包括DM1组生长板和关节软骨之间小梁骨的连接中断和分离增加。生物力学方面，DM1组的最大负荷、最大应力和应变参数显著低于对照组。1型糖尿病小鼠出现骨质流失，表现为骨体积/总体积、骨小梁数量、骨小梁厚度和骨密度降低。链脲佐菌素（STZ）注射显著上调高血糖组大鼠胫骨中血管紧张素Ⅱ1型受体（AT1R）、血管紧张素原（AGT）、肾素、肾素受体和血管紧张素转换酶（ACE）的mRNA表达，而血管紧张素Ⅱ2型受体（AT2R）、缓激肽B1受体（B1R）和缓激肽B2受体（B2R）的表达下调。DM1组肾素、ACE和血管紧张素Ⅱ（Ang II）的蛋白表达显著上调，而AT2R、B1R和B2R表达下调。
与对照组相比，高血糖治疗对骨骼有害，其潜在机制至少部分是通过局部骨骼中KKS活性下调和RAS活性上调介导的。
