目的 探讨氧化型低密度脂蛋白受体1(LOX-1)在大鼠残肾模型中的作用及他汀和沙坦类药物延缓慢性肾脏病(CKD)进展的可能机制.方法 SD大鼠制作残肾模型,残肾大鼠随机分为4组:残肾模型组、氯沙坦组、氟伐他汀组和联合用药组,假手术组作为正常对照.大鼠残肾模型制作1周后,氯沙坦组以氯沙坦30 mg·kg-1·d-1灌胃,氟伐他汀组以氟伐他汀15 mg·kg-1·d-1灌胃,联合用药组以氯沙坦和氟伐他汀组按上述剂量联合灌胃,假手术组和残肾模型组予等量溶剂灌胃,灌胃共8周.大鼠处死前,检测24 h尿蛋白和血尿素氮、肌酐和胆固醇、甘油三酯和LDL水平.RT-PCR检测肾脏LOX-1及单核细胞趋化蛋白-1(MCP-1)的表达,免疫组织化学检测肾脏及主动脉LOX-1的表达.结果 与假手术组比较,残肾模型组血肌酐、胆固醇、甘油三酯、LDL水平和尿蛋白定量明显增高(P<0.01);与残肾模型组相比,氯沙坦组、氟伐他汀组及联合用药组血肌酐、胆固醇、甘油三酯、LDL水平和尿蛋白定量明显下降(P<0.05).RT-PCR结果显示残肾大鼠肾脏LOX-1和MCP-1 mRNA表达明显增加(P<0.05),氯沙坦、氟伐他汀和联合应用明显下调了肾脏LOX-1和MCP-1的表达(P<0.05).免疫组化显示残肾大鼠肾间质和主动脉壁LOX-1表达明显增加,氯沙坦、氟伐他汀和联合用药均使LOX-1表达明显下调,并减轻了肾脏病理改变.结论 氯沙坦和氟伐他汀的肾脏保护作用可能部分与其对LOX-1表达的抑制及抗炎作用有关,二者联合应用可能具有协同作用.%Aim To investigate expression of lectin like oxidized low density lipoprotein receptor 1( LOX1 ) in rat remnant kidney model and the mechanism that underlies angiotensin II antagonists and statins retarding the progression of chronic kidney disease CKD ). Methods Sprague-Dawley rats were randomly selected to perform remnant kidney model operation and sham operated were as normal control. Remnant kidney rats were randomized into 4 groups: remnant kidney group, losartan treated group, fluvastatin treated group and combined-treatment group. One week after the operation, losartan ( 30 mg · kg-1 ·d-1 ) was administered daily by gavage to the rats in losartan treated group, fluvastatin( 15 mg · kg-1 ·d -1 ) in fluvastatin treated group, and losartan ( 30 mg· kg-1 · d-1 ) combined with fluvastatin( 15 mg ·kg-1 · d-1 ) in combined-treatment group. Equivalent solvent was given to the rats in sham operated group and remnant kidney group by gavage. 8 weeks later,urine was collected and 24 h urine protein was tested before the rats were killed. Serum urea nitrogen, creatinine, cholesterol and triglyeride were measured. LOX1 and MCP-1 expressions in kidney were evaluated by RT-PCR. LOX-1 expressions in kidney and aorta were determined by immunohistochemistry and histological changes in kidney were detected by pathological examination. Results Compared with sham operated group, serum creatinine, cholesterol, triglyeride and urine protein were markedly increased in remnant kidney group ( P ＜ 0. 01 ). Compared with remnant kidney group, serum creatinine, cholesterol, triglyeride and urine protein were significantly ameliorated in losartan .fluvastatin and combined treated group( P ＜ 0. 05 ).The result also showed that LOX-1 and MCP-1 expressions in kidneys and aortas were dramatically up-regulated in remnant kidney group( P ＜ 0. 05 ), and losartan. fluvastatin and coadministration greatly down-regulated the expressions of LOX-1 and MCP-1 , ameliorated renal pathological lesions ( P ＜ 0. 05 ). Conclusion The renoprotective effects of losartan and fluvastatin may partly correlate with the inhibition of LOX-1 expression and their anti-inflammatory effects, and they may have synergistic effects when combined used.
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