Sebeková Katarína, Lill Maria, Boor Peter, Heidland August, Amann Kerstin
Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, Bratislava, Slovakia.
Am J Nephrol. 2009;29(3):164-70. doi: 10.1159/000151771. Epub 2008 Aug 28.
BACKGROUND/AIMS: In experimental nephropathies, inhibitors of the renin-angiotensin-system (RAS) halted the progression, or even induced a regression in renal injury. We studied the potential of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin receptor blocker candesartan to reverse the established renal injury in the obese Zucker rat (OZR).
Forty 4-week-old OZRs were uninephrectomized and fed a high-protein diet. After 16 weeks, they were randomized into 4 groups (n = 10 each) with comparable proteinuria: (1) control group sacrificed immediately for baseline data, and groups gavaged daily for 8 weeks with (2) placebo, (3) perindopril (1 mg/kg/day), or (4) candesartan (10 mg/kg/day).
Both drugs reduced systolic blood pressure (perindopril -16%, p < 0.001; candesartan -10%, p < 0.05), renal hypertrophy, and proteinuria (perindopril to 32%; candesartan to 37% of pretreatment values). Glomerulosclerosis was halted (perindopril p < 0.001; candesartan p < 0.05), and the numbers of glomerular endothelial and podocyte cells were restored. Mesangiolysis was reversed by perindopril. Metabolic and oxidative parameters were either stabilized (perindopril), or improved (candesartan).
In the OZR late inhibition of RAS halts the progression of glomerulosclerosis, reverses mesangiolysis and prevents the decline in glomerular endothelial cell and podocyte numbers. Tubulointerstitial fibrosis and vascular injury remain unchanged. Proteinuria shows marked regression.
背景/目的：在实验性肾病中，肾素-血管紧张素系统（RAS）抑制剂可阻止疾病进展，甚至使肾损伤逆转。我们研究了血管紧张素转换酶（ACE）抑制剂培哚普利和血管紧张素受体阻滞剂坎地沙坦逆转肥胖 Zucker 大鼠（OZR）已形成的肾损伤的潜力。
40 只 4 周龄的 OZR 大鼠接受单侧肾切除术，并给予高蛋白饮食。16 周后，将它们随机分为 4 组（每组 n = 10），蛋白尿水平相当：（1）对照组立即处死以获取基线数据，其余组每天灌胃 8 周，分别给予（2）安慰剂、（3）培哚普利（1 mg/kg/天）或（4）坎地沙坦（10 mg/kg/天）。
两种药物均降低了收缩压（培哚普利降低 16%，p < 0.001；坎地沙坦降低 10%，p < 0.05）、肾肥大和蛋白尿（培哚普利降至治疗前值的 32%；坎地沙坦降至 37%）。肾小球硬化得到阻止（培哚普利 p < 0.001；坎地沙坦 p < 0.05），肾小球内皮细胞和足细胞数量得以恢复。培哚普利使系膜溶解得到逆转。代谢和氧化参数要么趋于稳定（培哚普利），要么得到改善（坎地沙坦）。
在 OZR 中，RAS 的晚期抑制可阻止肾小球硬化的进展，逆转系膜溶解，并防止肾小球内皮细胞和足细胞数量减少。肾小管间质纤维化和血管损伤保持不变。蛋白尿显著减轻。
