Effects Of Fluvastatin And Losartan On Lectin Like Oxidized Low Density Lipoprotein Receptor-1 Expression In Rat Remnant Kidney Model

Objective To investigate the effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor fluvastatin and angiotensin II antagonist losartan on lectin like oxidized low density lipoprotein receptor-1 expression in kidneys and aortas of rat remnant kidney model. To explore the effects of LOX-1 in chronic kidney disease (CKD) and the mechanism that underlies statins and angiotensin II antagonists retarding the progression of CKD.Methods Among 35 8-week-old Sprague-Dawley rats,28 were randomly selected to perform remnant kidney model operation and 7 were sham operated as normal control. Remnant kidney rats were randomized into 4 groups:remnant kidney model group, fluvastatin treated group, losartan treated group and combined-treatment group. One week after the operation, fluvastatin(15mg/kg·d) was administered daily by gavage to the rats in fluvastatin treated group, losartan(30mg/kg·d) in losartan treated group, and fluvastatin(15mg/kg·d) combined with losartan (30mg/kg·d) in combined-treatment group. Water was given to the rats in remnant kidney model group and combined-treatment group by gavage. 8 weeks later, urine was collected and 24h urine protein was tested before the rats were killed. Blood was drawn from aortas and then serum urea nitrogen, creatinine , cholesterol and triglyeride were measured. LOX-1 and MCP-1 expression in kidneys were evaluated by RT-PCR, LOX-1 expression in kidneys and aortas were determined by immunohistochemistry and histological changes in kidneys were detected by pathological examination.Results Compared with sham group, serum creatinine, cholesterol, triglyeride and urine protein were markedly increased in remnant kidney model group (P<0.01).Compared with remnant kidney model group, serum creatinine, cholesterol, triglyeride and urine protein were significantly ameliorated in fluvastatin treated group, losartan treated group and combined-treatment group(P<0.05),but showed no significant difference between fluvastatin treated group and losartan treated group (P>0.05). The result of RT-PCR showed that LOX-1 and MCP-1 mRNA expression were dramatically up-regulated in remnant kidney model group(P<0.05),and fluvastatin and losartan greatly down-regulated the expression of LOX-1 and MCP-1(P<0.05),coadministration of fluvastatin and losartan further inhibited LOX-1 and MCP-1 expression compared with two single-treated groups(P<0.05).The result of immumohischemistry revealed that LOX-1 expression in kidneys and aortas was significantly increased in remnant kidney model group, which was down-regulated by fluvastatin and losartan. And when combined treated, LOX-1 expression was more effectively inhibited in kidneys and aortas.Conclusion The expression of LOX-1 was evidently enhanced in the kidneys and aortas of rat remnant kidney model. Fluvastatin and losartan markedly down-regulated the expression of LOX-1 and MCP-1, lowered serum lipid and urine protein, ameliorated renal pathological lesions and improved renal function. And fluvastation combined with losartan may have synergistic effects. The renoprotective effects of fluvastatin and losartan may partly correlate with the inhibition of LOX-1 expression and their anti-inflammatory effects,which may reflect a new mechanism of fluvastatin and losartan in their renoprotective effects and contribute to the treatment of CKD.