Kelly D J, Zhang Y, Moe G, Naik G, Gilbert R E
Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia.
Diabetologia. 2007 Nov;50(11):2398-404. doi: 10.1007/s00125-007-0795-9. Epub 2007 Sep 8.
AIMS/HYPOTHESIS: Blockade of the renin-angiotensin system (RAS) with either ACE inhibitors or angiotensin receptor blocker is a key therapeutic strategy in slowing progression of diabetic nephropathy. Interruption of the RAS may also be achieved by blocking the activity of renin, the rate-limiting step in angiotensin II biosynthesis. However, it is not known whether drugs in this class also reduce the structural and functional manifestations of diabetic nephropathy.
Using diabetic transgenic (mRen-2)27 rats, a rodent model of advanced diabetic nephropathy, we compared the efficacy of the renin inhibitor, aliskiren (10 mg kg(-1) day(-1) by osmotic mini-pump), with the ACE inhibitor, perindopril (0.2 mg kg(-1) day(-1) in drinking water), over a 16 week period.
Both perindopril and aliskiren reduced blood pressure, albuminuria and structural injury in experimental diabetic nephropathy, although not to the same extent. Aliskiren, at the dose used, did not reduce systemic blood pressure as much as perindopril, but both compounds were equally effective in reducing albuminuria and glomerulosclerosis in diabetic animals. The magnitude of interstitial fibrosis was attenuated to a greater degree by aliskiren than by perindopril.
CONCLUSIONS/INTERPRETATION: These findings suggest that therapies aimed at different targets within the RAS may not have identical effects in attenuating structural injury in experimental diabetic nephropathy.
目的/假设：使用血管紧张素转换酶抑制剂（ACE 抑制剂）或血管紧张素受体阻滞剂阻断肾素-血管紧张素系统（RAS）是减缓糖尿病肾病进展的关键治疗策略。阻断肾素的活性（血管紧张素 II 生物合成的限速步骤）也可实现对 RAS 的阻断。然而，这类药物是否还能减轻糖尿病肾病的结构和功能表现尚不清楚。
我们使用糖尿病转基因（mRen-2）27 大鼠（一种晚期糖尿病肾病的啮齿动物模型），在 16 周的时间里，比较了肾素抑制剂阿利吉仑（通过渗透微型泵给药，剂量为 10 mg·kg-1·天-1）与 ACE 抑制剂培哚普利（饮用水中浓度为 0.2 mg·kg-1·天-1）的疗效。
培哚普利和阿利吉仑均可降低实验性糖尿病肾病的血压、蛋白尿和结构损伤，尽管程度有所不同。所用剂量的阿利吉仑降低全身血压的程度不如培哚普利，但两种化合物在降低糖尿病动物的蛋白尿和肾小球硬化方面同样有效。与培哚普利相比，阿利吉仑对间质纤维化程度的减轻作用更大。
结论/解读：这些发现表明，针对 RAS 内不同靶点的治疗方法在减轻实验性糖尿病肾病的结构损伤方面可能没有相同的效果。
