Tian He-lin, Zhao Chao-xian, Wu Hai-ying, Xu Zhong-xin, Wei Li-shun, Zhao Ru-tong, Jin Dong-ling
Medical College, Affiliated Hospital, Hebei University of Engineering, Handan, China.
Am J Med Sci. 2015 Jun;349(6):516-20. doi: 10.1097/MAJ.0000000000000451.
Vascular endothelial growth factor (VEGF) plays a critical role in the pathogenesis of diabetic microvascular complications. Finasteride has been confirmed to decrease VEGF expression in prostate and prostatic suburethral tissue resulting in limiting hematuria from human benign prostatic hyperplasia. The purpose of this study was to evaluate the effects of finasteride on microvessel density (MVD), VEGF protein and mRNA expressions in the renal tissue of diabetic rats.
Diabetic rats induced by streptozotocin were intragastrically given finasteride at 30 mg/kg body weight once a day for 4 weeks. Histomorphologic changes in kidney were observed under light microscope. Immunohistochemistry for CD34 and VEGF on kidney sections was performed to assess MVD and VEGF protein expression in glomeruli of rats, respectively. The VEGF mRNA expression in the renal tissue was examined using reverse transcription polymerase chain reaction analysis.
The glomerular tuft area, glomerular volume, MVD, VEGF protein expression in glomeruli and VEGF mRNA expression in the renal cortex tissue were significantly increased in diabetic rats and finasteride-treated rats when compared with controls (P < 0.01, P < 0.05). When compared with diabetic rats, the glomerular tuft area, glomerular volume, MVD, VEGF protein expression in glomeruli and VEGF mRNA expression in the renal cortex tissue of finasteride-treated rats were significantly decreased (P < 0.05, P < 0.01).
Finasteride reduces the VEGF expression and decreases the MVD in the renal tissue of diabetic rats, suggesting the therapeutic potential of finasteride on diabetic microvascular complications.
血管内皮生长因子(VEGF)在糖尿病微血管并发症的发病机制中起关键作用。非那雄胺已被证实可降低前列腺及前列腺尿道周围组织中VEGF的表达,从而减少人类良性前列腺增生所致的血尿。本研究旨在评估非那雄胺对糖尿病大鼠肾组织微血管密度(MVD)、VEGF蛋白及mRNA表达的影响。
用链脲佐菌素诱导的糖尿病大鼠,每天按30mg/kg体重灌胃给予非那雄胺,共4周。在光学显微镜下观察肾脏的组织形态学变化。分别对肾组织切片进行CD34和VEGF免疫组化,以评估大鼠肾小球中的MVD和VEGF蛋白表达。采用逆转录聚合酶链反应分析检测肾组织中VEGF mRNA的表达。
与对照组相比,糖尿病大鼠和非那雄胺治疗组大鼠的肾小球毛细血管丛面积、肾小球体积、MVD、肾小球VEGF蛋白表达及肾皮质组织VEGF mRNA表达均显著增加(P<0.01,P<0.05)。与糖尿病大鼠相比,非那雄胺治疗组大鼠的肾小球毛细血管丛面积、肾小球体积、MVD、肾小球VEGF蛋白表达及肾皮质组织VEGF mRNA表达均显著降低(P<0.05,P<0.01)。
非那雄胺可降低糖尿病大鼠肾组织中VEGF的表达并减少MVD,提示非那雄胺对糖尿病微血管并发症具有治疗潜力。