2型糖尿病模型GK大鼠骨形态学和生物力学特点观察

目的观察2型糖尿病模型GK大鼠的骨代谢特点以及骨密度和骨生物力学特性的变化。方法采用雄性6月龄GK大鼠10只,以月龄、性别匹配的健康Wistar大鼠作为正常对照。颈静脉取血检测与骨代谢有关的生化指标。DXA法测定股骨和腰椎骨密度,并行股骨三点弯曲实验和腰椎压缩实验。甲基丙烯酸甲酯包埋胫骨干骺端以制备不脱钙骨切片。应用多媒体病理图像分析软件进行骨组织形态计量学分析。结果GK大鼠体重明显低于健康对照Wistar大鼠（P〈0.01）。与对照组相比,GK大鼠血清骨钙素水平明显降低（4.97±0.49,6.75±0.71）μg/mL,P〈0.01],而抗酒石酸酸性磷酸酶活性明显升高（17.92±5.23,8.31±2.69）U/L,P〈0.01],但血钙和血磷无明显变化（P〉0.05）;股骨和腰椎骨密度显著降低（0.16±0.01,0.22±0.02;0.12±0.01,0.16±0.02）g/cm2,P〈0.01];骨强度和腰椎的弹性模量明显降低（P〈0.01）。骨形态学分析显示GK大鼠股骨长度和第五腰椎高度分别降低10.3%和9.5%（P〈0.01）,股骨和腰椎横截面积无明显变化（P〉0.05）。骨组织形态计量学分析显示,GK大鼠骨小梁体积、骨小梁厚度、类骨质表面和厚度明显降低（15.72±1.18,19.13±1.13）%,（61.91±4.54,74.43±3.63）μm,（18.18±1.25,19.63±1.07）%,（3.68±0.48,4.34±0.35）μm,P〈0.01或0.05],动态参数如矿化表面、矿化沉积率和骨形成率也明显降低（17.77±1.54,19.56±2.07）%,（1.07±0.22,1.35±0.16;0.20±0.03,0.26±0.04）μm/day,P〈0.05或0.01],而矿化延迟时间显著延长（2.66±0.56,2.12±0.35,P〈0.05）。结论非肥胖的GK大鼠表现有骨量减少和骨折危险性增加;2型糖尿病本身可干扰成骨细胞功能和活性而导致骨重建失衡。

Bone Histomorphometric and Biomechanical Analyses in Type 2 Diabetic Goto-Kakizaki Rats

Objective To characterize the bone metabolism in Goto-Kakizaki （GK） rats, a spontaneous type 2 diabetic model. Methods Ten six-month old male GK rats were enrolled, with ten age- and sex-matched non-diabetic Wistar rats as controls. Blood samples were collected from the carotid artery for analysis of calcium, phosphate, osteocalcin and tartrate-resistant acid phosphatase activity. Bone mineral density was assessed by a dual energy X-ray absorptiometry at the femur and the fifth vertebral body, respectively, followed by biomeehanieal studies. The metaphyseal tibiae were embedded in methylmethaerylate to obtain undecaleified sections. Histomorphometric analysis was performed with an analysis software for multimedia pathological image. Results The body weight was much lower in the GK rats than that in the healthy Wistar rats （ P 〈 0.01 ）. Compared with the controls, the GK rats had significantly lower serum osteoealein concentration （4.97±0.49, 6.75 ± 0.71 ） μg/mL] and higher tartrate-resistant acid phosphatase activity （17.92 ±5.23, 8.31± 2.69） U/L], both were P 〈 0.01. Bone density at the femur and lumbar vertebra was significantly deceased in the diabetic rats （0.16± 0.01, 0.22 ± 0.02; 0.12 ± 0.01, 0.16 ± 0.02） g/cm^2 , P 〈 0.01]. Bone morphologic analysis showed that the lengths of femur and lumbar were reduced by 10.3% and 9.5%, respectively, in the GK rats （P 〈 0.01 ）, while no significant difference was seen in the values of cross-sectional area at both sites （P 〉 0.05）. Histomorphometrical study showed significantly decreased trahecular bone volume, trabeeular thickness, osteoid surface and thickness in GK rats （15.72± 1.18,19.13±1.13）%, （61.91 ± 4.54, 74.43 ± 3.63） μm, （18.18 ± 1.25, 19.63± 1.07）%, （3.68± 0.48, 4.34 ± 0.35） μm, P 〈 0.01 or 0.05], respectively. Further, the mineralizing surface, mineral apposition rate and bone formation rate were also decreased in the GK rats compared with those in the controls （17.77± 1.