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目的 通过实验性动物模型观察细胞凋亡与肾小球硬化发生发展的相关性。方法 用一侧肾切除加静脉注射柔红霉素的方法建立大鼠肾小球硬化模型 ,应用原位末端转移酶标记技术 (TUNEL)观察细胞凋亡的发生。结果 ①建立的大鼠肾小球硬化模型 ,其组织形态学特征类似于人类局灶性节段性肾小球硬化的发生发展 ,第 4周开始出现硬化病灶 ,第 8周肾小球大部分节段均成为硬化病灶。②TUNEL结果显示 ,对照组大鼠肾组织中仅存在极少的细胞凋亡现象 ;肾小球硬化模型的肾组织 2周组无显著的细胞凋亡现象 ;4周组开始出现小球细胞凋亡现象 ,与对照组比较差异有显著性 [(5 .4± 1.2 )vs (1.6± 0 .8) ](P <0 .0 1) ;6周至 8周组小球细胞凋亡达高峰 ,凋亡细胞数分别为 (8.6± 2 .8) ,(10 .1± 1.9) ,与对照组比较 [分别为 (1.8± 0 .8) ,(1.7± 0 .5 ) ],差异有显著性 (P <0 .0 1)。③ 4周～ 8周 (硬化初、中期 ) ,硬化肾小球中出现的凋亡细胞数与肾小球细胞总数呈明显负相关(r =- 0 .85 ,P <0 .0 1) ;8周 (硬化后期 )以后 ,硬化肾小球内出现的凋亡细胞数与肾小球细胞总数呈正相关 (r=0 .91,P <0 .0 1)。结论 细胞凋亡与大鼠肾小球硬化发生的范围及进展的时相密切相关 ,细胞凋亡可能是引起肾小球固有细胞减少的重要机制之
Objective To observe the relationship between apoptosis and glomerulosclerosis by experimental animal model. Methods A rat model of glomerulosclerosis was established by one side nephrectomy plus intravenous injection of daunorubicin. The apoptosis was observed by TUNEL. Results ① The rat model of glomerulosclerosis was established. Its histomorphology was similar to that of focal segmental glomerulosclerosis in human. Sclerosing lesions began to appear in the fourth week, and the majority of glomeruli Segments become hardened lesions. ②TUNEL results showed that there were only few apoptotic cells in the kidney of rats in the control group, no significant apoptosis in the 2-week group of glomerulosclerosis rats and apoptosis of the glomerulus cells in the 4-week group (5 .4 ± 1.2 vs 1.6 ± 0.8)] (P <0.01). The apoptotic rate reached the peak at 6 weeks to 8 weeks, The numbers of dead cells were (8.6 ± 2 .8) and (10.1 ± 1.9), respectively, compared with those in the control group (1.8 ± 0.8 and 1.7 ± 0.5, respectively) P <0 .0 1). ③ The number of apoptotic cells in sclerosing glomeruli was negatively correlated with the total number of glomerular cells in 4 weeks ~ 8 weeks (early and middle sclerosis) (r = - 0.85, P <0.01); After 8 weeks (late stage of sclerosis), the number of apoptotic cells in sclerotic glomeruli was positively correlated with the total number of glomerular cells (r = 0.91, P <0.01). Conclusions Apoptosis is closely related to the extent and progression of glomerulosclerosis in rat. Apoptosis may be an important mechanism of glomerular innate cell decrease