辛伐他汀对阿霉素肾病大鼠的治疗作用及白细胞介素-1β表达的影响

Renoprotective effect of simvastatin on adriamycin-induced nephropathy in rats

目的观察炎症因子白细胞介素-1β(interleukin-1 beta,IL-1β)在阿霉素肾病大鼠发生肾小球硬化过程中的表达,探讨辛伐他汀保护阿霉素肾病大鼠肾脏的机制。方法雄性SD大鼠分为正常对照组、阿霉素肾病组(模型组)和阿霉素肾病辛伐他汀治疗组(治疗组),分别灌胃给药11周。免疫组化法观测肾组织中IL-1β的定位表达,半定量RT-PCR技术检测肾组织IL-1β mRNA的表达,酶联免疫吸附法检测血清和肾组织中IL-1β的水平,光镜观察肾小球硬化的情况。结果模型组肾组织IL-1β的表达明显增强(P<0.01),伴有明显的肾小球硬化及肾功能损害(P<0.01);与模型组比较,治疗组肾组织IL-1β的表达、肾小球硬化及肾功能损害均减轻(分别P<0.05、P<0.01、P<0.05)。结论辛伐他汀可能通过降低肾组织内IL-1β的表达,对肾脏起保护作用。

Objective To investigate the role of interleukin-1 beta （ IL-1 β） in glomerulosclerosis seconda- ry to adriamycin （ADR）-induced nephropathy in rats, and the effect of simvastatin on the expression of IL-1β. Methods Male Sprague-Dawley rats were randomly divided into normal control, ADR-induced nephropathy （model）, and simvastatin-treated ADR nephropathy （treatment） groups. After ADR-indueed nephropathy establishment in model and treatment groups, and eleven weeks of intragastrical administer of normal saline in normal control and model groups and of simvastatin in treatment group, the expression of IL-1β was detected by immunohistochemistry, RT-PCR and ELISA. Histopathological change of renal tissues was observed under light microscope, and glomerulosclerosis index （GSI） was also evaluated. Results Higher expression of IL-1β in kidney and GSI, as well as more severe loss of renal function were observed in model group than those in control group （ all P 〈 0.01 ）. Those changes were less severe in treatment group than in model group, suggesting treatment with simvastatin could significantly decrease the expression of IL-1β in kidney and GSI, and slow down the loss of renal function （P〈0.05, P〈0.01 and P〈0.05, respectively）. Conclusion The renoprotective effect of simvastatin may be via decreasing the expression of IL-1β in kidney.