Lu Yuan-Hang, Deng An-Guo, Li Ning, Song Ming-Na, Yang Xiao, Liu Jian-She
Department of Nephrology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Acta Pharmacol Sin. 2006 May;27(5):579-87. doi: 10.1111/j.1745-7254.2006.00289.x.
To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats.
Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry.
As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli.
During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.
研究内源性血管生成素在柔红霉素诱导的大鼠进行性肾小球硬化中的潜在病理作用。
将70只雄性Wistar大鼠随机分为柔红霉素组（DRB组，n = 40）和对照组（n = 30）。DRB组大鼠经尾静脉注射柔红霉素（15 mg/kg）。随后，在1、2、4、6、8和12周时，每组随机选取5只雄性Wistar大鼠进行24小时尿蛋白定量测定（24 h UPQM），并测定血浆肿瘤坏死因子α（TNF-α）、血管生成素-1（Ang1）和血管生成素-2（Ang2）水平。通过电子显微镜、高碘酸希夫（PAS）染色、免疫组织化学染色和原位杂交组织化学检查肾组织切片。
随着DRB组肾小球硬化的进展，肾小球中Ang1 mRNA和蛋白表达降低，而TNF-α蛋白、Ang2 mRNA和蛋白表达增加。肾小球中Ang1 mRNA和蛋白表达与24 h UPQM、Fn蛋白表达及细胞外基质平均面积（MAECM）呈负相关。相比之下，肾小球中Ang2 mRNA和蛋白表达与24 h UPQM、Fn蛋白表达及MAECM呈正相关；此外，血浆Ang2与24 h UPQM呈正相关。血浆TNF-α及肾小球中TNF-α表达与肾小球中Ang2 mRNA和蛋白表达呈正相关。肾小球中Ang1蛋白表达与Ang2蛋白表达呈负相关。
在柔红霉素诱导的肾小球硬化过程中，足细胞损伤导致肾小球中Ang1和Ang2平衡发生改变。血浆和肾小球中TNF-α升高可能上调肾小球中Ang2表达。血浆和肾小球中Ang2升高可能介导蛋白质通过肾小球滤过屏障的通透性。此外，Ang2的局部表达可能通过上调细胞外基质成分表达促进肾小球硬化进展。
