摘要
目的研究糖尿病大鼠肾皮质细胞凋亡的可能机制及其对糖尿病肾病的影响。方法20只雄性SD大鼠随机分为糖尿病组和对照组。糖尿病大鼠模型采用链脲佐菌素65 mg/kg腹腔注射诱导建立。12周后观察2组体质量、血糖以及血肌酐、尿素氮2、4 h尿蛋白等肾功能指标;采用透射电镜和原位末端标记法(TUNEL法)检测大鼠肾皮质细胞凋亡,并用免疫组织化学的方法检测增殖细胞核抗原(PCNA)以及凋亡相关基因Bax、Bcl-2、Caspase-3的表达。结果建模12周的糖尿病组肾小球和肾小管细胞凋亡明显增多(P<0.01),肾小球和肾小管细胞PCNA表达无明显差别(P>0.05);与对照组比较,糖尿病组肾小管Bax和Caspase-3表达明显增加(P<0.01),Bcl-2表达明显减少(P<0.05);2组肾小球都不表达Bax和Bcl-2,糖尿病组肾小球有少量Caspase-3表达。结论糖尿病大鼠肾皮质细胞过度凋亡。包括Bax、Bcl-2和Caspase-3在内的Caspase依赖的线粒体凋亡途径可能参与了糖尿病状态下肾小管细胞的凋亡;细胞凋亡的增多可能是糖尿病肾病发展的原因之一。
Objective To investigate the mechanisms of cell apoptosis in diabetic rat renal cortex and the effects of apoptosis on the development of diabetic nephropathy. Methods Twenty male Sprague-Dawley rats were randomly assigned to two groups: diabetic model group and control group. Diabetic rats were induced by intraperitoneal injection of streptozotocin(65 mg/kg). After 12 weeks, the body weight, serum glucose, serum creatinine, blood urea nitrogen and 24-hour urine protein excretion were checked. Apoptotic cells in renal cortex were checked by transmission electron microscope and terminal deoxynucleotidyl transferase-mediated d-UDP nick-end laheling(TUNEL). The expression of PCNA,Bax, Bcl-2 and Caspase-3 was examined by immunohistochemistry. Results Diabetes caused significantly increase in apoptosis in glomerular and tubular cells in renal cortex(P〈0.01). Compared with normal control group, the levels of Bax and Caspase-3 expression increased remarkably(P〈0.01), nil th lcant ose in and the level of Bcl-2 decreased significantly(P〈0.05) in renal cortical tubules in diabetic group. No expressions of Bax and Bcl-2 were detected in the glomerular cells of both groups. Caspase-3 expressed slightly increased in the glomeruli of diabetic group. Oonclusion Compared with the degree of cell proliferation, the cell apoptosis was relatively increased in the renal cortex of diabetic rats at 12th week. Activation of the Caspase-depedent apoptotic pathway by increasing the expression of Bax, Caspase-3 and decreasing the expression of Bcl-2 may contribute to apoptosis in renal cortical tubular cells of diabetic rats. Excessive apoptosis may play an important role in the development of diabetic nephropathy.
出处
《福建医科大学学报》
2006年第5期447-451,共5页
Journal of Fujian Medical University
基金
福建省教育厅科研基金资助项目(K02081)
关键词
糖尿病肾病
增殖细胞核抗原
凋亡
大鼠
diabetic nephropathies
proliferating cell nuclear antigen
apoptosis
rats