Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Sharkia Gov., Zagazig, Egypt.
J Pharm Pharmacol. 2012 Jun;64(6):862-71. doi: 10.1111/j.2042-7158.2012.01508.x. Epub 2012 Mar 30.
Aliskiren is the first in a new class of orally active direct renin inhibitors, approved for the treatment of hypertension. However, the efficacy of aliskiren in diabetic cardiovascular complications remains to be defined. This study aimed to test the hypothesis that aliskiren may enhance the beneficial effects of pioglitazone against cardiovascular injury associated with diabetic nephropathy.
Diabetic nephropathy was induced in rats by unilateral nephrectomy followed by streptozotocin injection. Diabetic nephropathic rats were orally given vehicle, pioglitazone, aliskiren, or combined pioglitazone and aliskiren for four weeks to compare their effects on cardiovascular injury, particularly myocardial fibrosis.
Pioglitazone treatment significantly attenuated cardiac lipid peroxidation, oxidative injury and myocardial fibrosis in diabetic nephropathic rats. This was associated with up-regulation of transforming growth factor-β1 and matrix metalloproteinase-2 genes, along with down-regulation of tissue inhibitor of metalloproteinase-2 gene in cardiac tissue. The combination of aliskiren with pioglitazone exerted greater beneficial effect than monotherapy with either drug, on all the aforementioned parameters.
Our findings suggested that aliskiren enhanced the protective effects of pioglitazone against myocardial fibrosis, in experimental diabetic nephropathy. Thus, the combination of aliskiren and pioglitazone may be a potential therapeutic strategy for cardiovascular injury associated with diabetic nephropathy.
阿利克仑是一类新型的口服活性直接肾素抑制剂，已被批准用于治疗高血压。然而，阿利克仑在糖尿病心血管并发症中的疗效仍有待确定。本研究旨在验证阿利克仑可能增强吡格列酮对糖尿病肾病相关心血管损伤的有益作用这一假设。
通过单侧肾切除术和链脲佐菌素注射诱导大鼠糖尿病肾病。糖尿病肾病大鼠给予 vehicle、吡格列酮、阿利克仑或吡格列酮和阿利克仑联合治疗 4 周，以比较它们对心血管损伤的影响，特别是心肌纤维化。
吡格列酮治疗显著减轻了糖尿病肾病大鼠的心脏脂质过氧化、氧化损伤和心肌纤维化。这与心脏组织中转化生长因子-β1 和基质金属蛋白酶-2 基因的上调以及组织金属蛋白酶抑制剂-2 基因的下调有关。阿利克仑与吡格列酮联合应用比单独使用任一药物在所有上述参数上都具有更大的有益作用。
我们的研究结果表明，阿利克仑增强了吡格列酮对实验性糖尿病肾病中心肌纤维化的保护作用。因此，阿利克仑和吡格列酮的联合应用可能是治疗糖尿病肾病相关心血管损伤的一种潜在治疗策略。
