2型糖尿病肾病并发骨质疏松大鼠模型研究

目的构建2型糖尿病肾病并发骨质疏松大鼠模型。方法选用SD大鼠,通过喂养高糖高脂饲料4周后,予以链脲佐菌素(STZ 35 mg/kg)进行腹腔注射,继续喂养4周后观察血糖、尿量、尿蛋白及Ca、P等生化指标变化,通过双能X线测量骨密度以及进行生物力学检测骨强度,并取肾、骨组织进行病理检测。结果造模组在高糖高脂饲料喂养后,血糖、尿量及尿蛋白较正常组均逐渐升高,在第4周腹腔注射链脲佐菌素后,造模组的血糖、尿量及尿蛋白较正常组显著升高。在第8周时,造模组的血糖、尿量、尿蛋白及尿Ca、P均明显高于正常组,差异有统计学意义。造模组的骨密度及骨骼强度低于正常组。病理显示造模组大鼠出现肾脏肥大,肾小球毛细血管袢肥大,系膜基质增多肾脏病变以及骨小梁稀疏、变细、连续性中断等骨骼病变。结论通过腹腔注射链脲佐菌素联合8周高糖高脂饮食可建立2型糖尿病肾病并发骨质疏松的大鼠模型,该模型具有高糖、多尿、尿蛋白增加、骨密度下降以及肾小球病变和骨吸收增加的特点。

Study on the model of type 2 diabetic nephropathy with osteoporosis in rats

Objective To establish and evaluate the rat model of type 2 diabetic nephropathy with osteoporosis. Methods SD rats were fed with high glucose and high fat diet for 4 weeks. Then they were injected with streptozotocin (STZ 35 mg/kg) intraperitoneally. The changes of blood glucose, urine volume, urine protein, CA, P, and other biochemical indexes were observed. Bone mineral density and biomechanical strength were measured using dual energy X-ray absorptiometry. The kidney and bone tissue were collected for pathological detection. Results The levels of blood glucose, urine volume, and urine protein in rats of the model group increased gradually compared with those in the normal group after feeding with high glucose and high fat diet. After injecting streptozotocin intraperitoneally for 4 weeks, the levels of blood glucose, urine volume, and urine protein in rats of the model group increased significantly compared with those in the normal group. At the 8th week, the levels of blood glucose, urine volume, urine protein, and urine Ca and P in rats of the model group were significantly higher than those of the normal group, and the difference was statistically significant. Bone mineral density and bone strength in rats of the model group were lower than those of the normal group. Pathological findings showed that the rats in the model group had renal hypertrophy, glomerular capillary loop hypertrophy, mesangial matrix increase, renal lesions, and bone lesions such as sparseness, thinning, and continuous interruption of bone trabecula. Conclusion The rat model of type 2 diabetic nephropathy with osteoporosis can be established by intraperitoneal injection of streptozotocin combined with high glucose and high fat diet for 8 weeks. The model has the characteristics of high glucose, polyuria, increased urine protein, decreased bone density, increased glomerulopathy, and bone absorption.