Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Department of Zoology, Institute of Sciences, Banaras Hindu University, Varanasi 221005, India.
Biomed Pharmacother. 2017 Sep;93:276-285. doi: 10.1016/j.biopha.2017.06.045. Epub 2017 Jun 23.
Kidney hypoxia represents a unifying mechanism in the pathogenesis of diabetic nephropathy. Hypoxia-induced factor (HIF)-1α mediates the metabolic responses of renal hypoxia by modulating the expression of VEGF. In the present study, we investigated the effect of Pueraria tuberosa extract (PTY-2r) on the expression of HIF-1α, VEGF and nephrin in streptozotocin (STZ) induced diabetic nephropathy (DN).
The model of diabetic nephropathy (DN) was produced by intraperitoneal injection of 55mg/kg of STZ and maintained for 60days. These DN-rats were randomly divided into three groups, i.e., DN, DN+PTY-2r (100mg/100g), and DN+PTY-2r (50mg/100g). A normal control (NC) group was administrated with drug vehicle. Expression of HIF-1α, VEGF and nephrin were evaluated in the renal tissue.
Blood glucose, urine protein, serum creatinine, and urea, level were significantly raised along with decreased creatinine clearance in DN rats. Immunofluorescence and Western blot analysis showed significantly increased expression of HIF-1α & VEGF and decreased expression of nephrin in DN control rats. The PTY-2r treatment significantly reversed these changes in a dose-dependent manner. Correlation analysis showed that the expression of VEGF was positively correlated with that of HIF-1α and negatively correlated with nephrin.
The PTY-2r can improve the chronic hyperglycemic condition induced kidney damage, and may delay the development of diabetic nephropathy by inhibiting the expression of HIF-1α and VEGF, thereby restoring the expression of nephrin.
肾缺氧是糖尿病肾病发病机制中的一个统一机制。缺氧诱导因子 (HIF)-1α 通过调节血管内皮生长因子 (VEGF) 的表达来介导肾缺氧的代谢反应。在本研究中，我们研究了野葛提取物 (PTY-2r) 对链脲佐菌素 (STZ) 诱导的糖尿病肾病 (DN) 中 HIF-1α、VEGF 和 Nephrin 表达的影响。
采用腹腔注射 55mg/kg STZ 制作糖尿病肾病 (DN) 模型，维持 60 天。这些 DN 大鼠随机分为三组，即 DN、DN+PTY-2r（100mg/100g）和 DN+PTY-2r（50mg/100g）。正常对照组给予药物载体。评估肾组织中 HIF-1α、VEGF 和 Nephrin 的表达。
DN 大鼠血糖、尿蛋白、血清肌酐和尿素水平升高，肌酐清除率降低。免疫荧光和 Western blot 分析显示，DN 对照组 HIF-1α 和 VEGF 表达明显增加，Nephrin 表达明显减少。PTY-2r 治疗呈剂量依赖性显著逆转这些变化。相关性分析表明，VEGF 的表达与 HIF-1α 的表达呈正相关，与 Nephrin 的表达呈负相关。
PTY-2r 可改善慢性高血糖引起的肾脏损伤，通过抑制 HIF-1α 和 VEGF 的表达，恢复 Nephrin 的表达，可能延缓糖尿病肾病的发展。
