高血糖和蛋白尿促进肾小管上皮细胞凋亡Hyperglycemia and Proteinuria Promote Apoptosis of Renal Tubular Epithelial Cells
桂华珍,阎秀英,肖瑛,石明隽,张国忠
GUI Huazhen1,YAN Xiuying2,XIAO Ying2,SHI Mingjun2,ZHANG Guozhong2 (1.Department of Function Laboratory
摘要(Abstract):
目的:探讨糖尿病(DM)病程中高血糖和蛋白尿与肾小管上皮细胞凋亡的关系。方法:SD大鼠随机分为对照组和糖尿病组,注射链脲佐菌素(STZ)诱导糖尿病,分别于糖尿病2周、4周、8周、16周和24周处死动物;检测血糖和24 h尿蛋白量,免疫组织化学检测Bcl-2和Bax蛋白表达,TUNEL法检测细胞凋亡。结果:与对照组相比,DM大鼠出现明显高血糖并且持续高水平,DM组2周起24 h尿蛋白增多并随病情进展而加重;TUNEL检测显示,对照组和DM组2周大鼠肾小管上皮细胞未见凋亡,而DM组24周大鼠部分肾小管可见凋亡细胞;免疫组化结果显示,DM组2周大鼠肾小管上皮细胞Bcl-2蛋白和Bax蛋白均明显高于对照组,然而DM组8周Bcl-2蛋白表达开始减少,Bax蛋白则随DM进展而增多,Bax/Bcl-2比值亦随之增高,并且与24 h尿蛋白呈正相关。结论:糖尿病病程中,高血糖和持续增多的蛋白尿使肾小管上皮细胞Bax/Bcl-2比值增高,促进肾小管上皮细胞凋亡。
Objective: To explore the relation of hyperglycemia and proteinuria to apoptosis of renal tubular epithelial cells in the diabetic course.Methods: Sprague-Dawley rats were randomly divided into control group and diabetic group.Diabetic models were established by injection with streptozotocin(STZ).Rats were sacrificed in 2,4,8,16 and 24 weeks(groups DM2w,DM4w DM8w DM16w and DM24w) respectively.Blood glucose and 24h urine protein were examined with biochemistry method.Immunochemistry was employed to detect the expression of Bcl-2 and Bax protein.Cell apoptosis was detected with TUNEL method.Results: Compared with control animals,diabetic rats presented a sustained high level of blood glucose;The 24h urine protein increased along with the progress of the di-sease since the 2nd week.TUNEL staining didn't show apoptotic cell in renal tubules in either control group or group DM2w.While in group DM 24w,several apoptotic cells were found in renal tubules.Immunochemistry exhibited that both Bcl-2 and Bax proteins in group DM2w were much higher than those in control group.The Bax protein increased progressively,but Bcl-2 protein decreased since the 8th week.The ratio of Bax/Bcl-2 therefore increased and was positively correlated with 24 h urine protein.Conclusion: Hyperglycemia and progressively increasing proteinuria promote apoptosis of renal tubular cells perhaps by up-regulating the ratio of Bax/Bcl-2.
关键词(KeyWords):
高血糖症;蛋白尿;肾小管;细胞凋亡;免疫组织化学;大鼠,Sprague-Dawley
hyperglycemia;proteinuria;kidney tubules;apoptosis;immunohistochemistry;rats,Sprague-Dawley
基金项目(Foundation): 高等学校博士学科点基金[20060660001];; 贵州省科技计划课题[黔科合SY字(2008)3042]
作者(Author):
桂华珍,阎秀英,肖瑛,石明隽,张国忠
GUI Huazhen1,YAN Xiuying2,XIAO Ying2,SHI Mingjun2,ZHANG Guozhong2 (1.Department of Function Laboratory
DOI: 10.19367/j.cnki.1000-2707.2011.05.004
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- 高血糖症
- 蛋白尿
- 肾小管
- 细胞凋亡
- 免疫组织化学
- 大鼠,Sprague-Dawley
hyperglycemia - proteinuria
- kidney tubules
- apoptosis
- immunohistochemistry
- rats,Sprague-Dawley
- 桂华珍
- 阎秀英
- 肖瑛
- 石明隽
- 张国忠
GUI Huazhen1 - YAN Xiuying2
- XIAO Ying2
- SHI Mingjun2
- ZHANG Guozhong2 (1.Department of Function Laboratory
- 桂华珍
- 阎秀英
- 肖瑛
- 石明隽
- 张国忠
GUI Huazhen1 - YAN Xiuying2
- XIAO Ying2
- SHI Mingjun2
- ZHANG Guozhong2 (1.Department of Function Laboratory