Transforming growth factor-beta1, vascular endothelial growth factor, and bone morphogenic protein-7 expression in tacrolimus-induced nephrotoxicity in rats.
Transforming growth factor-beta1, vascular endothelial growth factor, and bone morphogenic protein-7 expression in tacrolimus-induced nephrotoxicity in rats.
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他克莫司诱导的大鼠肾毒性中转化生长因子-β1、血管内皮生长因子和骨形态发生蛋白-7 的表达。
DOI：
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发表时间：
2006
影响因子：
0.9
通讯作者：
E. Akoĝlu
中科院分区：
文献类型：
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作者：
B. Oğütmen;S. Tuğlular;F. Cakalagaoglu;C. Ozener;E. Akoĝlu
本研究的目的是研究转化生长因子（TGF）-β 1、血管内皮生长因子（VEGF）和骨形态发生蛋白-7（BMP-7）在慢性他克莫司（TAC）毒性大鼠模型中的表达与健康对照组相比。将17只雄性Wistar大鼠分为两组：第1组动物为健康对照组，第2组动物接受TAC治疗（每天1 mg/kg，腹腔注射8周）。在研究期结束时，在肾功能研究（包括血尿素氮（BUN）、血清肌酐和肌酐清除率）后处死动物，并通过光学显微镜检查肾组织的他克莫司毒性结果，特别是传入小动脉病和间质纤维化。TGF-β 1、VEGF和BMP-7的表达通过免疫化学染色标本的半定量评分进行评估。第2组的平均TAC水平为5.53 +/- 2.38 ng/mL。第2组与第1组的BUN、肌酐水平和肌酐清除率分别为57.99 +/- 11.13 vs 39.49 +/- 5.64 mg/dL; 0.60 +/- 0.16 vs 0.65 +/- 0.09 mg/dL; 0.97 +/- 0.39 vs 1.17 +/- 0.32 mL/min。与第1组相比，第2组中仅BUN水平显著较高。与第1组相比，第2组的传入小动脉病变和间质纤维化显著增加。与第1组相比，第2组TGF-β 1和VEGF表达显著增加，而BMP-7表达显著降低。总之，我们的研究结果表明，TAC诱导的肾毒性与TGF-β 1和VEGF的增加和BMP-7的表达减少有关。
The aim of our study was to investigate transforming growth factor (TGF)-beta1, vascular endothelial growth factor (VEGF), and bone morphogenic protein-7 (BMP-7) expression in the rat model of chronic tacrolimus (TAC) toxicity compared to healthy controls. Seventeen male Wistar rats were divided into two groups: group 1 animals were healthy controls and Group 2 animals were treated with TAC (1 mg/kg per day intraperitoneally for 8 weeks). At the end of the study period the animals were sacrificed following renal function studies including blood urea nitrogen (BUN), serum creatinine, and creatinine clearance, and renal tissues were examined by light microscopy for the findings of tacrolimus toxicity, specifically for afferent arteriolopathy and interstitial fibrosis. TGF-beta1, VEGF, and BMP-7 expression were assessed by semiquantitative scoring of the immunohistochemically stained specimens. Mean TAC levels were 5.53 +/- 2.38 ng/mL in group 2. BUN, creatinine levels, and creatinine clearance were 57.99 +/- 11.13 vs 39.49 +/- 5.64 mg/dL; 0.60 +/- 0.16 vs 0.65 +/- 0.09 mg/dL; 0.97 +/- 0.39 vs 1.17 +/- 0.32 mL/min in group 2 versus group 1. Only the BUN level was significantly higher in group 2 compared to group 1. Afferent arteriolopathy and interstitial fibrosis were significantly increased in group 2 compared to group 1. TGF-beta1 and VEGF expression was significantly increased while BMP-7 expression was significantly decreased in group 2 versus group 1. In conclusion, our findings suggest that TAC-induced nephrotoxicity is associated with increased TGF-beta1 and VEGF and decreased BMP-7 expression.