转录因子GADDl53/CHOP的激活与糖尿病大鼠肾组织固有细胞凋亡的关系初探

APOPTOSIS INDUCED BY GADD153/CHOP INVOLVED IN DIABETIC KIDNEY DISEASE

目的检测内质网应激(endoplasmic reticulum stress,ERS)标志蛋白:葡萄糖调节蛋白(GRP78/Bip)、转录因子GADDl53/CHOP在糖尿病大鼠肾脏细胞中表达及其与肾脏固有细胞凋亡之间的关系,初步探讨ERS在糖尿病肾损害中的作用及机制。方法单侧肾切除大鼠腹腔注射链脲佐菌素诱发糖尿病,于8周应用免疫组织化学检测GRP78、GADDl53/CHOP的表达与定位,TUNEL染色检测细胞凋亡部位,流式细胞术检测细胞凋亡程度,并对GRP78、GAD-Dl53/CHOP表达水平进行半定量分析,同时观察尿蛋白、BUN、尿肌酐等反应肾功能的相关指标。结果建模8周,糖尿病大鼠较正常组的肾细胞凋亡率明显升高,GRP78、GADDl53/CHOP表达明显增加。结论糖尿病肾损害过程中,ERS被诱导并可能通过激活转录因子GADDl53/CHOP引起肾脏细胞过多丢失,在糖尿病肾病的发病机制中起重要作用。

Objective To investigate the expressions of GRP78,GADDl53/CHOP and their relationship with apoptosis in renal cortex of diabetic rats.Methods Uninephrectomized Wistar rats were used to induce diabetes by intraperitoneal injection of STZ（65mg/kg）.After 8 weeks,the expression and distribution of GRP78 and GADDl53/CHOP were examined by immunohistochemistry or Flow cytometry.Apoptosis was evaluated by TUNEL labeling and flow cytometry.Serum creatinine,blood urea nitrogen and 24-hour urine protein excretion were checked.Results Compared with those of the control group,the numbers of apoptotic cells and the expressions of GRP78 and GADDl53/CHOP in renal tubule and glomerulus were much higher in the diabetic kidneys at 8 weeks.Conclusion Activation of endoplasmic reticulum stress may play an important role in the development of diabetic nephropathy.