STZ诱导联合高脂饮食及右肾切除糖尿病肾病模型大鼠病程早、中、晚期的界定

Definition of Early,Middle and Late Stages of Diabetic Nephropathy Model Rats

目的:探索糖尿病肾病(DN)模型大鼠不同病程阶段(早、中、晚期)的造模时间。方法:采用右肾切除+腹腔注射链脲佐菌素+高脂饮食建立DN大鼠模型(DN模型组),对照组予假手术及普通饲料喂养。观察26周。定期检测大鼠体重、尿微量白蛋白(m Alb)、24 h尿蛋白定量(24 h U-Pr)、血糖、Scr、BUN、肾脏病理等,观察模型大鼠进入DN早、中、晚期的时间。结果:DN模型组大鼠在右肾切除、STZ腹腔注射3天后测尿m Alb升高,24 h U-Pr> 30 mg,此时为DN早期阶段(记为0周)。第9周末,DN模型大鼠24 h U-Pr(123. 40±22. 15) mg/24 h,显著高于对照组(9. 05±1. 92) mg/24 h(P <0. 01);电镜下见肾小球GBM增厚(0. 28μm),足细胞结构不清,数目减少,此时进入DN中期阶段。第22周末,DN模型大鼠血BUN(13. 52±1. 26) mmol/L,Scr(73. 42±3. 51)μmol/L,较对照组[BUN(6. 31±1. 44) mmol/L,Scr(39. 25±2. 92)μmol/L]显著升高(P <0. 01)。光镜下见DN大鼠肾小球荒废,毛细血管节段性硬化;电镜下测GBM厚约0. 35μm,足细胞数目明显减少,足突排列紊乱、大片融合。此时进入DN晚期阶段。结论:右肾切除+高脂饲料+STZ腹腔注射3天后大鼠DN造模成功,此时为DN早期。DN成模9周后进入DN中期,22周后进入DN晚期。

Objective:To explore the modeling time of different stages(early,middle and late)in diabetic nephropathy(DN)model rats.Methods:DN rat model was established by right kidney resection plus intraperitoneal injection of streptozotocin and high-fat diet(DN model group).The control group was given sham surgery and normal feed.Observed for 26 weeks.Regularly measure rat body weight,urine microalbumin(m Alb),24 h urine protein quantitation(24 h U-Pr),blood glucose,serum creatinine(Scr),urea nitrogen(BUN),kidney pathology,to observe the time when the model rats entered the early,middle and late stages of DN.Results:In the DN model group,the urine m Alb was increased after 3 days of right kidney resection and STZ intraperitoneal injection,and 24 h U-Pr>30 mg,which was the early stage of DN(recorded as 0 weeks).At the 9 th weekend,the 24 h U-Pr of DN model rats continuously increased(123.40±22.15)mg/24 h,which was significantly higher than that of the control group(9.05±1.92)mg/24 h(P<0.01).Electron microscopy showed Glomerular basement membrane thickening(0.28μm),the podocyte structure was unclear,the number decreased.At this point,model rats enter middle stage of DN.At the end of the 22 nd week,the BUN of DN model rats was(13.52±1.26)mmol/L,Scr(73.42±3.51)μmol/L,which was significantly higher than that of the control group(BUN(6.31±1.44)mmol/L,Scr(39.25±2.92)μmol/L,P<0.01)Under light microscopy,DN rat glomerular waste and capillary segmental sclerosis,under the electron microscope,the basement membrane was about 0.35μm,the number of podocytes was significantly reduced,and the foot processes were disordered and large-scale fusion.At this point model rats into the late stage of DN.Conclusion:After 3 days of right kidney resection and high fat diet plus STZ intraperitoneal injection,the DN model rat was successful established,which was early stage of DN.After 9 weeks of DN molding,it entered the middle stage of DN,and after22 weeks,it entered the late stage of DN.