Delhi Institute of Pharmaceutical Sciences and Research, India.
J Renin Angiotensin Aldosterone Syst. 2013 Mar;14(1):3-13. doi: 10.1177/1470320312452766. Epub 2012 Jul 12.
Aliskiren, a direct renin inhibitor (DRI), has therapeutic effects in patients with hypertension and associated complications, but its potential mechanism in diabetic nephropathy is lacking. The effects of aliskiren in Streptozotocin (STZ)-induced renal complication in diabetic rats were investigated. Aliskiren treatment for eight weeks at the dose of 10 mg/kg/day, via osmotic mini-pump, induced improvement in blood glucose levels, systolic blood pressure (BP) and serum creatinine. Improvement of insulin resistance by aliskiren was confirmed by increased glucose translocation in liver and muscle and hence insulin levels. The treated group also showed improvement in glomerulosclerosis and tubulointerstitial injury. Aliskiren treatment also improved albumin levels in plasma, suppressed profibrotic and proinflammatory cytokine synthesis viz TNF-α and TGF-β and angiogenesis by a decrease in VEGF. In addition, the level of total proteins and GFR via cystatin c and beta-2microglobulin along with adiponectin and erythropoietin were also improved. These results suggest that the beneficial organ protective effect of aliskiren is mediated by improvement in insulin resistance as well as a direct anti-fibrotic effect in the target organ in STZ-induced diabetic rats with a slight effect on blood pressure. Aliskiren may be a useful therapeutic agent in the treatment of type 2 diabetes and diabetic nephropathy.
阿利克仑，一种直接肾素抑制剂（DRI），在高血压及相关并发症患者中具有治疗效果，但在糖尿病肾病中的潜在作用机制尚不清楚。本研究旨在探讨阿利克仑在链脲佐菌素（STZ）诱导的糖尿病大鼠肾脏并发症中的作用。通过渗透压微型泵，以 10mg/kg/天的剂量，给予阿利克仑治疗 8 周，可改善血糖水平、收缩压（BP）和血清肌酐。阿利克仑通过增加肝脏和肌肉中的葡萄糖转运，从而提高胰岛素水平，证实了其改善胰岛素抵抗的作用。治疗组的肾小球硬化和肾小管间质损伤也得到改善。阿利克仑治疗还可改善血浆中的白蛋白水平，抑制 TNF-α和 TGF-β等促纤维化和促炎细胞因子的合成以及血管生成，从而降低 VEGF。此外，通过胱抑素 C 和β2-微球蛋白以及脂联素和促红细胞生成素，总蛋白和 GFR 水平也得到改善。这些结果表明，阿利克仑的有益器官保护作用是通过改善胰岛素抵抗以及在 STZ 诱导的糖尿病大鼠靶器官中的直接抗纤维化作用介导的，对血压的影响较小。阿利克仑可能是治疗 2 型糖尿病和糖尿病肾病的一种有用的治疗药物。
