不同剂量阿霉素致大鼠局灶节段硬化肾病模型的建立比较

目的探讨不同剂量阿霉素对大鼠局灶节段硬化肾病模型的影响。方法左侧肾切除加尾静脉注射不同剂量阿霉素致大鼠肾脏局灶节段性硬化,观察不同剂量阿霉素对模型大鼠成活率、24 h尿蛋白定量、血清肌酐、尿素氮、肾脏病理的影响。结果不同阿霉素注射剂量组大鼠4周、8周成活率随着注射剂量的升高呈逐渐下降趋势,且4周、8周时阿霉素注射剂量4.5～6 mg/kg组模型大鼠成活率均低于50%;8周时成活率与注射剂量呈高度显著性负相关（r=0.9045,P〈0.01）。各阿霉素注射剂量组于1周出现尿蛋白明显升高（P〈0.01）、2周出现血清肌酐明显升高（P〈0.01）、4周出现血清尿素氮明显升高（P〈0.01）,并均呈进行性增高,2周时除3 mg/kg组外,其余各组血清尿素氮较正常组高（P〈0.01,P〈0.05）;8周时各注射剂量组大鼠24 h尿蛋白定量、血清肌酐、血清尿素氮与阿霉素注射剂量呈高度显著性正相关（r=0.942 9,P〈0.01;r=0.938 4,P〈0.01;r=0.956 8,P〈0.01）。各组大鼠肾脏病理均提示肾小球出现局灶节段硬化表现,且硬化程度随注射剂量的增加而呈加重趋势。结论阿霉素尾静脉注射剂量3 mg/kg模型组大鼠死亡率低,同时大鼠肾脏病理又能表现出符合人类肾小球局灶节段硬化的改变,是较为理想的造模剂量。

Establishment and comparison of the focal segmental glomurular sclerosis nephrosis rat model with different dosage adriamycin to induce

Objective To explore the effect of adriamycin with different doses used for the focal segmental glomurular sclerosis nephrosis rat model Methods The focal segmental glomurular sclerosis nephrosis rat induced by left nephrectomy plus intravenous injection with different adriamycin doses, to observe the effect of different adriamycin doses on rat model of survival rate,24-hour urinary protein excretion, serum creatinine, urea nitrogen, and kidney pathology. Results the survival rate decreased with the increase of injection dosage in different doses group and survival rate of injection dosage of 4. 5 mg/kg - 6 mg/kg was reduced to less than 50% at fourth week and eighth week, survival rate had a significant negative correlation with injection dosage at eighth week （ r = 0. 904 5, P 〈 0.01 ）. Each group of injection dosage appeared urinary protein significantly increased at first week（ P 〈 0. 01 ）, serum creatinine significantly increased at second week（P 〈 0. 01 ）and urea nitrogen significantly increased at fourth week（P 〈 0. 01 ）, and all showed progressive increase, serum urea nitrogen of each group is higher than the normal except the 3 mg/kg group（ P 〈0. 01 ,P 〈 0. 05 ） , 24- hour urinary protein excretion, serum creatinine and urea nitrogen had a significant positive correlation with injection dosage at eighth week （ r = 0. 942 9, P 〈 0.01 ; r = 0.938 4, P 〈 0. 01 ; r = 0. 956 8, P 〈 0. 01 ）. Renal pathology of all groups showed focal segmental glomurular sclerosis, and the hardening degree aggravation while injection dosage rising. Conclusion Mortality of 3mg/kg group is Lowest and accord with human focal segmental glomurular sclerosis,it is the more ideal dose of adriamycin rat model.