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KMID : 0882420040670060615
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Korean Journal of Medicine
2004 Volume.67 No. 6 p.615 ~ p.624
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The anti-inflammatory effects of angiotensin II blockade in animal model of cyclosporine-induced nephropathy
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Song Joon-Chang
Kim Yong-Soo
Yang Chul-Woo
Chang Yoon-Sik
Bang Byung-Kee
Shin Mi-Jung
Woo Seong-Yong
Yoon Hye-Eun
Chun Yeon-Joo
Hyoung Bok-Jin
Woo Hyun-Young
Choi Bum-Soon
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Abstract
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Background: Long-term treatment of immunosuppresant CsA causes interstitial inflammation and fibrosis in the kidney. Renin-angiotensin system (RAS) plays the most important role in the pathogenesis CsA-induced renal injury. Accordingly we evaluated the anti-inflammatory effect of angiotensin II blockades using losartan (LSRT) in a rat model of chronic CsA nephropathy.
Methods: Male Sprague-Dawley rats, initially weighing 225 to 250 g, were used. After 1 week of a low-salt diet (0.05% sodium), the rats were randomized into four groups and treated for 4 weeks. The Vehicle (VH) group was treated with olive oil. The VH+LSRT group was treated with olive oil and LSRT. The CsA group received CsA. The CsA+LSRT group was simultaneously treated with CsA and LSRT. The anti-inflammatory effect of LSRT was evaluated with C-reactive protein (CRP) expression, osteopontin (OPN) mRNA and protein expression, and ED-1 infiltration.
Results: The CsA treatment caused an increase in serum creatinine and a decrease in creatinine clearance compared with that of the VH group. Intrarenal CRP positive cells were significantly decreased in the CsA+LSRT group compared with the CsA group (38.0±2.1 vs. 65.0±5.1, p<0.01). In the CsA group, the degree of OPN mRNA expression was increased compared with that of the VH group. But, OPN mRNA expression was decreased in the CsA+LSRT group (387.5±46.6% vs. 719.8±58.5%, p<0.05). In the degree of ED-1 infiltration, we had a similar results such as CRP and OPN mRNA expression (CsA group 30.5±8.0 vs. CsA+LSRT 86.0±11.0, p<0.01).
Conclusion: We concluded that the anti-inflammatory effects of angiotensin II blockade has a potential protective effect against CsA-induced renal injury.(Korean J Med 67:615-624, 2004)
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KEYWORD
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Cyclosporine nephropathy, Angiotensin II blockade, C-reactive protein, Osteopontin, ED-1
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