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[内质网应激及其特异性凋亡途径半胱天冬酶-12与糖尿病大鼠肾皮质细胞凋亡的关系]

[The relationship between endoplasmic reticulum stress and its particular apoptosis way caspase-12 and apoptosis in renal cortex of diabetic rats].

作者信息

Cao Yan-Ping, Hao Yong-Mei, Liu Qing-Juan, Wang Jian, Li Hang, Duan Hui-Jun

机构信息

Department of pathology, Hebei Medical University, Shijiazhuang 050017, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2011 May;27(2):236-40.

Abstract

OBJECTIVE

To investigate the expressions of 78-kDa glucose-regulated protein (GRP78) and Caspase-12 and their relationship with apoptosis in renal cortex of diabetic rats.

METHODS

Uninephrectomized Wistar rats were used to induce diabetes by intraperitoneal injection of Streptozotocin (STZ 65 mg/kg). After 8 weeks, the expression and distribution of GRP78, Caspase-12, proliferating cell nuclear antigen (PCNA) were examined by immunohistochemistry. Flow cytometry was used to detect the levels of protein of GRP78 and Caspase-12. Apoptosis was evaluated by means of terminal deoxynucleotidyl transferase-mediated d-UDP nick-end labeling (TUNEL) and Flow cytometry. Serum creatinine, blood urea nitrogen and 24-hour urine protein excretion were checked.

RESULTS

Compared with those in normal control group, the numbers of apoptosis and the expression of GRP78, Caspase-12 in glomerular and tubular cells were much higher in the diabetic kidneys at 8 weeks. There was no significant difference between group A and group B.

CONCLUSION

Activation of endoplasmic reticulum stress may play an important role in the development of diabetic nephropathy.

摘要

目的

探讨78 kDa葡萄糖调节蛋白(GRP78)和半胱天冬酶-12(Caspase-12)在糖尿病大鼠肾皮质中的表达及其与细胞凋亡的关系。

方法

采用单侧肾切除的Wistar大鼠,腹腔注射链脲佐菌素(STZ 65 mg/kg)诱导糖尿病。8周后,采用免疫组织化学法检测GRP78、Caspase-12、增殖细胞核抗原(PCNA)的表达及分布。采用流式细胞术检测GRP78和Caspase-12蛋白水平。采用末端脱氧核苷酸转移酶介导的d-UDP缺口末端标记法(TUNEL)和流式细胞术评估细胞凋亡。检测血清肌酐、血尿素氮和24小时尿蛋白排泄量。

结果

与正常对照组相比,糖尿病大鼠肾脏8周时肾小球和肾小管细胞凋亡数量及GRP78、Caspase-12表达明显升高。A组和B组之间无显著差异。

结论

内质网应激激活可能在糖尿病肾病的发生发展中起重要作用。

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