糖尿病大鼠肾小球转化生长因子β_1和血管内皮生长因子的表达A Study on the Relationship between Expression of TGF-β_1 and VEGF and ECM Deposition in Glomeruli of Diabetic Rats
郭兵,肖瑛,张翠
GUO Bing, XIAO Ying, ZHANG Cui(Department of Pathophysiology, Guiyang Medical College, Guiyang 550004, China)
摘要(Abstract):
目的:观察糖尿病大鼠肾小球转化生长因子β1(TGF-β1)和血管内皮生长因子(VEGF)表达的动态变化,探讨其与细胞外基质沉积以及肾损害之间的关系。方法:雄性W istar大鼠随机分为正常对照组(A组),糖尿病1周组(B组),糖尿病4周组(C组),糖尿病8周组(D组)。用链脲菌素复制糖尿病模型;免疫组织化学法检测TGF-β1、VEGF和纤维连接蛋白(FN)在肾小球的表达情况;HE和PAS染色,光镜观察动物肾组织形态;生化法测定血糖、血肌酐及尿蛋白。结果:正常肾小球内可见少量VEGF表达,而未见TGF-β1表达。糖尿病1周肾小球内可见TGF-β1表达,而VEGF表达无明显增加;糖尿病4周组和糖尿病8周组肾小球内TGF-β1和VEGF表达显著增多,且两者呈正相关,而且糖尿病4周组肾小球内TGF-β1及VEGF的表达与24 h尿蛋白量之间呈正相关。糖尿病4周组和糖尿病8周组肾小球内FN的表达显著高于正常对照组。结论:大鼠糖尿病状态诱导肾小球内TGF-β1和VEGF表达增加,可能在糖尿病肾病大鼠高滤过、蛋白尿和肾小球肥大以及纤维化发病中起作用。
Objective: To observe the dynamic changes of transforming-growth factor (TGF-β_1) and vascular endothelial growth factor (VEGF) in glomeruli of diabetic rats and to investigate their roles in the development of diabetic nephropathy (DN). Methods: Wistar male rats were randomly divided into normal control (group A),diabetic group of one week (group B),diabetic group of four weeks (group C), and diabetic group of eight weeks (group D). Diabetic rat model was established by peritoneal injection of streptozotocin (STZ). Immunohistochemistry was used to detect the expression of TGF-β_1,VEGF and fibronectin (FN) in the kidney. The morphological changes of renal tissue were examined under microscopy on sections stained with HE and PAS. Blood glucose (BG), serum creatinine (Scr) and urine protein (UP) were checked with biochemical methods. Results: The expression of VEGF and FN but not TGF-β_1 was observed in normal renal tissue. Positive staining of TGF-β_1 was observed in the glomeruli in group B. A continuous increase of TGF-β_1 and VEGF expression was observed in group C and group D. The expression of TGF-β_1 and VEGF were positively correlated with 24h UP in group C and group D respectively. The FN expression was significantly higher in glomeruli of groups C and D than in those of group A. Conclusions: Our data suggest that during the DN process a continuous increase of TGF-β_1 and VEGF play an important role in the rising of glomerular filtration rate, 24h UP and lead to renal hypertrophy and fibrosis.
关键词(KeyWords):
糖尿病肾病;转化生长因子β;纤连蛋白类;蛋白尿;血管内皮生长因子
diabetic nephropathies; transforming growth factor beta; fibronectins; proteinuria; vascular endothelial growth factor
基金项目(Foundation):
作者(Author):
郭兵,肖瑛,张翠
GUO Bing, XIAO Ying, ZHANG Cui(Department of Pathophysiology, Guiyang Medical College, Guiyang 550004, China)
DOI: 10.19367/j.cnki.1000-2707.2005.04.003
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文章评论(Comment):
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- 糖尿病肾病
- 转化生长因子β
- 纤连蛋白类
- 蛋白尿
- 血管内皮生长因子
diabetic nephropathies - transforming growth factor beta
- fibronectins
- proteinuria
- vascular endothelial growth factor
- 郭兵
- 肖瑛
- 张翠
GUO Bing - XIAO Ying
- ZHANG Cui(Department of Pathophysiology
- Guiyang Medical College
- Guiyang 550004
- China)
- 郭兵
- 肖瑛
- 张翠
GUO Bing - XIAO Ying
- ZHANG Cui(Department of Pathophysiology
- Guiyang Medical College
- Guiyang 550004
- China)