大鼠阿霉素肾病超微结构转变过程实验研究

目的探讨单侧肾切除加重复注射阿霉素制作的大鼠局灶节段性肾小球硬化动物模型肾脏超微结构的变化过程,为采用阿霉素肾病模型提供实验基础。方法2个月龄雌性SD大鼠38只,随机分为对照组(18只)和阿霉素肾病组(ADR组,20只)。ADR组大鼠先行右肾切除,其后第1周和第2周分别给予阿霉素5mg/kg和3mg/kg尾静脉注射,对照组行假手术和等量生理盐水静脉注射。在切肾后第4、8、16周收集血标本测定血肌酐(Scr)和尿液测定24h尿蛋白定量,各时间点处死6只大鼠取其残肾行光镜组织病理学观察及电镜超微结构观察。结果ADR组Scr和尿蛋白在各时间点均较对照组显著升高(P<0.05);ADR组大鼠肾脏组织病理损害进行性发展,在第16周时形成FSGS改变;电镜下早期以肾小球足细胞广泛融合为主,在第8周时有少部分修复,16周时出现肾小球硬化;肾小管上皮细胞主要表现为大量线粒体肿胀和空泡变损伤。结论单侧肾切除加重复注射阿霉素可成功诱导局灶节段性肾小球硬化大鼠动物模型,其超微结构变化包括肾小球和肾小管双重损伤,若干预需早期进行。

Ultrastructural Observation of adriamycin induced focal segmental glomerularsclerosis in rats

Objective To observe the ultrastructural changes of adriamycin induced focal segmental glomerularsclerosis in rats.Methods Female SD rats were divided into normal control group and adriamycin renal disease (ADR) group randomly.ADR group were carried out unilateral nephrectomy and injected with 5mg/kg and 3mg/kg of adriamycin via tail vein at the 1st and 2nd week after nephrectomy,while the control group rats were carried out sham operation and 0.9% Sodium Chloride solution injection of equal volume.The urine protein and Serum creatinine (Scr) were measured 0w (before operation),4w,8w,and 16w after nephrectomy,while the renal histological and ultrastructural changes were evaluated.Results The proteinuria and Scr were more severe in ADR group than that in control group.In ADR group,mesangial proliferation and the tubular-interstitial fibrosis were more remarkable than that in control group.The results of electron microscope showed that the podocytes leisions in ADR group were more severe than that of control group at the 16th week,and the main changes were focused on podocytes and tubular epithelial cells.Conclusion After the second injection,the changes of kidney are like those in minimal change glomerulonephritis of human being.The kidney have the changes of focal segmental glomeralosclerosis.