Deoxycorticosterone Acetate-salt 고혈압 유발 신장손상에서 Tamoxifen의 치료효과
Effects of Tamoxifen in Deoxycorticosterone Acetate-salt Hypertensive Nephropahty
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Background: The present study was designed to evaluate the possible renoprotective effects of tamoxifen in deoxycorticosteroneacetate (DOCA)-salt hypertensive (DSH) rats and its role in inflammation and fibrosis in the kidney. Methods: MaleSprague-Dawley rats, weighing 180 to 200 g, were used. All rats underwent unilateral nephrectomy. One week later, one groupof rats (n = 8) was implanted with DOCA strips (200 mg/kg) and another group of rats (n = 8) was implanted with DOCAstrips with co-treated with tamoxifen (10 mg/kg) through gavage feeding. Rats that did not implanted DOCA strips served ascontrols (n = 6). Two weeks later, the systolic blood pressure (SBP) was measured by tail-cuff method. The protein expressionof transforming growth factor-β (TGF-β), Smad, α-smooth muscle actin (α-SMA), E-cadherin, ED-1, cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS) was determined in the kidney by immunoblotting. The mRNA expression oftumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1)was determined by real-time polymerase chain reaction. Results: In DSH rats, SBP was increased, which was not affected bytamoxifen treatment. Serum creatinine level was comparable in DSH rats compared with controls, which was not affected bytamoxifen treatment. In DSH rats, the protein expression of TGF-β, Smad 2/3, Smad 4, α-SMA, ED-1, COX-2, iNOS wasincreased compared with controls, and these changes were attenuated by tamoxifen treatment except that of TGF-β. ThemRNA expression of TNF-α, MCP-1, and VCAM-1 was increased, and expression of MCP-1 and VCAM-1 was counteractedby tamoxifen treatment. Conclusions: Tamoxifen is effective in preventing the progression of nephropathy in DSH rats, themechanism of which is associated with anti-inflammation and anti-fibrotic effects.
Abstract
Background: The present study was designed to evaluate the possible renoprotective effects of tamoxifen in deoxycorticosteroneacetate (DOCA)-salt hypertensive (DSH) rats and its role in inflammation and fibrosis in the kidney. Methods: MaleSprague-Dawley rats, weighing 180 to 200 g, were used. All rats underwent unilateral nephrectomy. One week later, one groupof rats (n = 8) was implanted with DOCA strips (200 mg/kg) and another group of rats (n = 8) was implanted with DOCAstrips with co-treated with tamoxifen (10 mg/kg) through gavage feeding. Rats that did not implanted DOCA strips served ascontrols (n = 6). Two weeks later, the systolic blood pressure (SBP) was measured by tail-cuff method. The protein expressionof transforming growth factor-β (TGF-β), Smad, α-smooth muscle actin (α-SMA), E-cadherin, ED-1, cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS) was determined in the kidney by immunoblotting. The mRNA expression oftumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1)was determined by real-time polymerase chain reaction. Results: In DSH rats, SBP was increased, which was not affected bytamoxifen treatment. Serum creatinine level was comparable in DSH rats compared with controls, which was not affected bytamoxifen treatment. In DSH rats, the protein expression of TGF-β, Smad 2/3, Smad 4, α-SMA, ED-1, COX-2, iNOS wasincreased compared with controls, and these changes were attenuated by tamoxifen treatment except that of TGF-β. ThemRNA expression of TNF-α, MCP-1, and VCAM-1 was increased, and expression of MCP-1 and VCAM-1 was counteractedby tamoxifen treatment. Conclusions: Tamoxifen is effective in preventing the progression of nephropathy in DSH rats, themechanism of which is associated with anti-inflammation and anti-fibrotic effects.
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