细胞凋亡与大鼠肾小球硬化关系的初步探讨

Relationship between Apoptosis and Experimental Glomerulosclerosis in Rats

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 。

Objective To study the relationship between apoptosis and glomerulosclerosis by establishing an experimental animal model of glomerulosclerosis. Methods The rat model of glomerulosclerosis was established by left nephrectomy and intravenous injection of Daunomycin (model group, n=30). The other 30 rats (control group) were injected with normal saline at the same time as the model group. Apoptosis was assayed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) in the two groups. Results ① The features of renal histopathology of the model group rats was resembled primary focal segmental glomerulosclerosis in human. ② No significant apoptosis was noted within two weeks in either the control group or the model group. The phenomenon of apoptosis initiated at 4th week. The level of apoptosis in the model group was significantly higher than that in the control group [( 5.4 ± 1.2 ) vs ( 1.6 ± 0.8 )] (P< 0.01 ) at 4th week. The number of apoptotic cells reached the highest level at 6th and 8th weeks ( 8.6 ± 2.8 and 10.1 ± 1.9 , respectively) compared with the control group ( 1.8 ± 0.8 , 1.7 ± 0.5 , respectively) (P< 0.01 ). ③ The total number of apoptotic cells was negatively correlated to the number of glomerular cells from 4th to 8th weeks (r= -0.85 , P< 0.01 ); however, there was a positive correlation between them after 8 weeks (r= 0.91 , P< 0.01 ) in the model group. Conclusions There is a significant correlation between apoptosis and glomerulosclerosis. Apoptosis might play an important role in decreasing glomerular resident cells.