糖尿病大鼠肾脏细胞凋亡与Bax和Bcl-2基因表达

Apoptosis and expression of Bax and Bcl-2 in the kidney of diabetic rats

目的 观察糖尿病大鼠肾脏细胞凋亡、Bax和 Bcl- 2表达及二者的相关性。 方法 单侧肾切除大鼠腹腔注射链脲佐菌素诱发糖尿病 ,采用原位末端标记法检测肾脏细胞凋亡 ;流式细胞术和免疫组化检测肾皮质 Bax和 Bcl- 2表达水平 ;原位杂交检测 Bax和 Bcl- 2 m RNA表达 ,并观察尿蛋白、BU N、尿肌酐等反映肾功能的有关指标。 结果 在制模后 2、4、8、12周时 ,糖尿病组大鼠较对照组肾小球、肾小管凋亡细胞数明显增多 ,Bax、Bcl- 2蛋白和 m RNA的表达显著增强 (P<0 .0 5 )。随着大鼠糖尿病病程延长 ,肾功能恶化 ,肾脏凋亡细胞数逐渐增多 ,Bax表达亦逐渐增强 ,Bax/Bcl- 2比增加 ,且肾脏凋亡细胞数与 Bax及 Bax/Bcl- 2比具有相关性 (P<0 .0 5 )。 结论 肾脏凋亡细胞的不断增加可能是糖尿病肾病发生、发展的原因之一 ,Bax和 Bcl- 2可能参与肾脏细胞凋亡的调控。

Objective To investigate the relationship between apoptosis and the expression of Bax and Bcl 2 in the kidney of diabetic rats. Methods Uninephrectomized SD rats were used to induce diabetes by intraperitoneal injection of STZ (65 mg/kg). Apoptosis was evaluated by means of terminal deoxynucleotidyl transferase mediated d UTP nick end labeling (TUNEL). Flow cytometry, immunohistochemistry and in situ hybridization were used to detect the protein and mRNA of Bax and Bcl 2. Parameters of renal function such as excretion of urinary protein, BUN, Ccr were also detected. Results Compared with those in the kidneys of control group, apoptotic cells were more in number and the expression of Bax and Bcl 2 was higher in the diabetic kidneys at week 2,4,8,12 ( P <0.05). Further, the number of apoptotic cells and the Bax/Bcl 2 ratio increased gradually ( P <0.05), and they were significantly correlated. Conclusion Apoptosis in the diabetic kidney may play a role in the progression of diabetic nephropathy. The change in Bax and Bcl 2 activities may be responsible for apoptosis in diabetic kidney.