Department of Nephrology, Chungnam National University Hospital, Daejeon, South Korea.
J Urol. 2011 Aug;186(2):694-701. doi: 10.1016/j.juro.2011.03.122. Epub 2011 Jun 17.
Renin-angiotensin system activation is involved in inflammation and fibrosis in the kidney. Aliskiren, a direct renin inhibitor, decreases renin-angiotensin system activation, including plasma renin activity and angiotensin II, but increases the prorenin level, which may promote inflammation and fibrosis in renal tissue. Thus, we evaluated whether inhibiting the renin-angiotensin system by aliskiren would decrease renal inflammation and fibrosis in a mouse model of unilateral ureteral obstruction.
Ten-week-old male C57BL/6 mice (Samtako, Kyoung Gi-Do, Korea) weighing 30 to 33 gm were divided into 4 groups, including vehicle or aliskiren treated sham operated and vehicle or aliskiren treated unilateral ureteral obstruction groups. We evaluated plasma renin activity, and plasma renin and renal mRNA expression levels of renin and (pro)renin receptor. To evaluate inflammation and fibrosis renal mRNA expression of monocyte chemotactic protein-1, osteopontin and transforming growth factor-β was measured. Hematoxylin and eosin, Masson's trichrome staining, and immunohistochemical staining for CD68, transforming growth factor-β and α-smooth muscle actin were performed.
Plasma renin activity was significantly lower in the aliskiren treated obstruction group than in the vehicle treated obstruction group. Aliskiren treatment increased renal mRNA expression of renin. The number of CD68 positive cells, and renal monocyte chemotactic protein-1 and osteopontin mRNA levels were significantly higher in mice with unilateral ureteral obstruction than in sham operated mice. Aliskiren decreased the increased levels of these inflammation markers. Aliskiren also decreased renal transforming growth factor-β mRNA expression, transforming growth factor-β and α-smooth muscle actin immunostaining, and Masson's trichrome stained areas of unilateral ureteral obstruction kidneys.
Aliskiren has anti-inflammatory and antifibrotic effects in an experimental unilateral ureteral obstruction mouse model.
肾素-血管紧张素系统的激活与肾脏的炎症和纤维化有关。阿利克仑，一种直接肾素抑制剂，可降低肾素-血管紧张素系统的激活，包括血浆肾素活性和血管紧张素 II，但增加前肾素水平，这可能促进肾脏组织的炎症和纤维化。因此，我们评估了阿利克仑抑制肾素-血管紧张素系统是否会减少单侧输尿管梗阻小鼠模型中的肾脏炎症和纤维化。
10 周龄雄性 C57BL/6 小鼠（Samtako，Kyoung Gi-Do，韩国）体重 30 至 33 克，分为 4 组，包括假手术对照的载体或阿利克仑处理组，以及假手术对照的载体或阿利克仑处理的单侧输尿管梗阻组。我们评估了血浆肾素活性，以及血浆肾素和肾 mRNA 表达水平的肾素和（前）肾素受体。为了评估炎症和纤维化，测量了单核细胞趋化蛋白-1、骨桥蛋白和转化生长因子-β 的肾 mRNA 表达。进行了苏木精和伊红、马松三色染色以及 CD68、转化生长因子-β 和α-平滑肌肌动蛋白的免疫组织化学染色。
与载体处理的梗阻组相比，阿利克仑处理的梗阻组的血浆肾素活性显著降低。阿利克仑治疗增加了肾 mRNA 表达的肾素。与假手术组相比，单侧输尿管梗阻小鼠的 CD68 阳性细胞数以及肾单核细胞趋化蛋白-1 和骨桥蛋白 mRNA 水平显著升高。阿利克仑降低了这些炎症标志物的升高水平。阿利克仑还降低了肾转化生长因子-β mRNA 表达、转化生长因子-β 和α-平滑肌肌动蛋白免疫染色以及单侧输尿管梗阻肾脏的马松三色染色面积。
阿利克仑在单侧输尿管梗阻小鼠模型中具有抗炎和抗纤维化作用。
