洛伐他汀联合厄贝沙坦对梗阻性肾病大鼠骨桥蛋白及肾间质纤维化的影响

Effect of union treatment of lovastatin and irbesartan on osteopontin expression and tubulointerstitial fibrosis in obstructive nephropathy rats

目的探讨洛伐他汀联合厄贝沙坦对单侧输尿管梗阻大鼠骨桥蛋白(OPN)表达及肾间质纤维化的影响。方法将试验用SD大鼠随机分为4组(n=10):假手术对照组、单侧输尿管结扎组(UUO组)、厄贝沙坦组(60mg/L)、联合治疗组(洛伐他汀20mg/L联合厄贝沙坦60mg/L)。对照组及模型组仅予等量生理盐水灌胃。观察各组大鼠第6周肾功能、24h尿蛋白和肾组织病理学改变,并检测肾组织骨桥蛋白的表达。结果与模型组比较,厄贝沙坦治疗能使OPN的表达降低(P<0.05),使24h尿蛋白及血清肌酐(Scr)降低(P<0.05),肾组织病理损害减轻,肾小管间质面积较模型组显著减少(P<0.01);而洛伐他汀联合厄贝沙坦治疗后,OPN的表达降低更为显著,肾功能及肾组织病理损害改善更为明显。结论洛伐他汀联合厄贝沙坦可明显降低单侧输尿管梗阻大鼠肾小管间质OPN的表达,减轻肾小管间质纤维化而发挥肾脏保护作用。

Objective To investigate the effects of union treatment of lovastatin and irbesartan on the expression of osteopontin （OPN） and renal tubulointerstitial fibrosis. Methods Experimental SD rats were randomly divided into four groups （n = 10） respectively：sham operation group,unilateral ureteral ligation operation group （UUO group）,irbesartan group （60 mg/L） and combination group （with 20 mg/L lovastatin combined 60 mg/L irbesartan）.The rats in sham operation group and UUO group were treated with equal normal saline.After 6 weeks,observing renal function,histopathological changes and 24-hours proteinuria,and detecting the expression of OPN in renal interstitium. Results Irbesartan treatment could reduce the expression of OPN compared with model group （ P 0.05）,24 h urinary albumin and serum creatinine （Scr） decreased （P 0.05） and alleviate the damages of renal histopathology,renal tubular interstitial area was significantly reduced in the model group （P 0.01）;And lovastatin combined irbesartan treatment,the expression of OPN reduced more significantly,renal function and kidney pathology damage improvement was more obvious. Conclusion By the combined treatment of lovastatin and irbesartan,the expression of OPN is significantly decreased and renal interstitial fibrosis is obviously ameliorated in obstructive nephropathy rats.