Aliskiren attenuates proteinuria in mice with lupus nephritis by a blood pressure-independent mechanism

作者：Yen T H^*; Yang H Y; Yeh Y H; Chu P H; Wen C J; Fu J F; Wang I K; Liang C C; Chang C T; Chen K H; Tian Y C; Hung C C; Lin J L; Yang C W

来源：Lupus, 2013, 22(2): 180-189.

DOI：10.1177/0961203312471871

• Direct renin inhibitor
• aliskiren
• lupus nephritis
• blood pressure
• proteinuria
• non-invasion in vivo imaging system

This study revealed that low-dose aliskiren treatment could attenuate proteinuria by interrupting the renin-angiotensin system in mice with lupus nephritis, and the beneficial effect was beyond blood pressure control. An in and ex vivo fluorescence imaging (using a non-invasion in vivo imaging system) showed intense labeling of renin in the kidneys of female MRL/lpr mice. In the study, Alzet mini-osmotic pumps were implanted into 6-week-old female MRL/lpr mice. Pumps were filled with either phosphate-buffered saline or a solution of aliskiren dissolved in phosphate-buffered saline (20 mg/kg/day) and replaced at 28-day intervals. Mice were sacrificed at four and eight weeks. To label cells for DNA synthesis, bromodeoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally an hour prior to sacrifice. The level of renin inhibition was adequate, as aliskiren-treated mice demonstrated higher renal renin mRNA expression than controls (p %26lt; 0.05). Although there were no significant differences in the systolic blood pressure (control versus aliskiren-treated: 127.20 +/- 4.44 mmHg versus 103.80 +/- 7.40 mmHg, p %26gt; 0.05) and heart rate (control versus aliskiren-treated: 680.50 +/- 11.71 versus 647.80 +/- 13.90, p %26gt; 0.05) of both groups after eight weeks, there was significant reduction of inflammatory cytokines (transforming growth factor-beta1, regulated on activation normal T cell expressed, monocyte chemoattractant protein-1 and osteopontin, p %26lt; 0.05), reduction of innate immunity (toll-like receptor 7, p %26lt; 0.05), as well as a reduction of glomerular proliferation and inflammation (BrdU-, CD45-, CD3- and F4/80-positive glomerular cells, p %26lt; 0.01) after aliskiren infusion, which might translate into an improvement in proteinuria (control versus aliskiren-treated: 493.7 versus 843.7 mg/g, p %26lt; 0.01) or weight gain (control versus aliskiren-treated: 5.65 +/- 1.61 versus 8.67 +/- 0.97%, p %26lt; 0.05). Lupus (2013) 22, 180-189.

• 出版日期2013-2
• 单位长春大学; 中国医科大学