Effects Of Losartan On Glomerular Microvascular Endothelium Injury's Repair In The Remnant Kidney Model

Objective The study investigated effects of AngiotensionⅡ(AngⅡ) receptor blocker(ARB),losartan on glomerular microvascular endothelium injury's repair in the remnant kidney model.This study will provide new theoretical and experimental evidences for ARB in the treatment of chronic kidney disease.Methods Thirty-two Sprague-Dawley rats weighing 200-250g were randomized to three groups.The sham group underwent sham surgery consisting of laparotomy and manipulation of both kidneys before wound closure.The other 24 rats all underwent subtotal nephrectomy performed by right subcapsular nephrectomy and infarction of approximately two-thirds of the left kidney by selective ligation of two of three to four extrarenal branches of the left renal artery.Animals were then randomly assigned to two groups:remnant kidney model group or losartan treated group(25mg·kg^-1·d^-1).Dissolvent was given to the rats in sham group and remnant kidney model group.15 weeks later,urine was collected and 24h urine protein was tested before the rats were killed.Blood was drawn from heart and then serum albumn, urea nitrogen,creatinine,cholesterol and triglyeride were measured.RECA-1 expression in kidneys was determined by immunohistochemistry and histological changes in kidneys were detected by periodic acid-silver masson stain(PASM).VEGF and TSP-1 expression in kidneys were determined by RT-PCR and Western blot.Results1.Compared with sham group,serum urea nitrogen,creatinine,cholesterol, triglyeride and 24h urine protein were markedly increased in remnant kidney model group(P＜0.05).Compared with remnant kidney model group,serum urea nitrogen, creatinine,cholesterol,triglyeride and 24h urine protein were significantly ameliorated in losartan treated group(P＜0.05).But serum albumn showed no significant difference among sham group,remnant kidney model group and losartan treated group(P＞0.05).2.Kidney histopathology showed the glomerularsclerosis index(GSI)was higher in remnant kidney model group than in sham group(0.89±0.12 vs 0.29±0.05,P＜0.05), but losartan markedly reduced the GSI in remnant kidney model(0.34±0.02 vs 0.89±0.12,P＜0.05).3.Kidney immunohistochemistry showed glomerular capillary endothelium density was lower in remnant kidney model group than in sham group(1.99±0.31 vs 7.21±0.57,P＜0.05),but losartan markedly increased the glomerular capillary endothelium density in remnant kidney model(5.93±0.70 vs 1.99±0.31,P＜0.05).4.Losartan significantly increased mRNA(0.2+0.02 vs 0.12+0.01,P＜0.01) and protein(0.16±0.04 vs 0.05±0.02,P＜0.01) expression of VEGF in remnant kidney tissue and decreased renal TSP-1 expression(P＜0.01).Conclusion1.Losartan markedly reduced the serum cholesterol,triglyeride and 24h urine protein excretion and improved renal function.2.Losartan increased remnant renal tissue glomerular capillary endothelium density and attenuated glomerular fibrosis in remnant kidney model.3.Campared with remnant kidney model group,losartan increased VEGF expression and decreased TSP-1 expression.4.Losartan,which has been shown to be able to slow the progressive loss of renal microvascular endothelium,may work in part by effect VEGF and TSP-1's expression.