LDLr表达失衡在阿霉素肾病大鼠肾小球硬化中的作用

摘要

Objective:To observe the expression of low density lipoprotein receptor ( LDLr) , sterol regulatory element bind-ing protein-2 (SREBP-2) in kidney of glomerulosclerosis secondary to adriamycin (ADR) induced nephrosis rats, and the under-lying mechanism of lipid-mediated renal injury and renoprotective effect of statins. Methods:Male Sprague-Dawley rats were ran-domly divided into control, ADR nephrosis, and simvastatin-treated ADR nephrosis groups. After 12 weeks of therapy, the expres-sion of LDLr and SREBP-2 were detected by reverse transcription-polymerase chain reaction and Western-blot assay, the choles-terol in kidney was measured by enzymic colorimetric method and Oil red O staining, and glomerulosclerosis index ( GSI) was also e-valuated. Results:Compared with the control group, the expression of LDLr and SREBP-2, cholesterol in kidney and the GSI were all significantly increased in ADR nephrosis group (all P<0. 01). Treatment with simvastatin could significantly decrease the expres-sion of LDLr and SREBP-2, the accumulation of cholesterol in kidney and the GSI were also decreased (P<0. 05 or P<0. 01, re-spectively) . Linear Regression analysis showed that the accumulation of cholesterol in kidney was associated with the upregulation of LDLr and SREBP-2 (all P<0. 01). Conclusion:The effects of failure of LDLr expression may be responsible for the accumulation of cholesterol in kidney during glomerulosclerosis secondary to adriamycin-induced nephrosis rats, the renoprotective effect of simvasta-tin may attribute to decreasing the expression of LDLr.%目的：观察阿霉素肾病大鼠肾小球硬化过程中低密度脂蛋白受体( LDLr)的表达情况,及辛伐他汀对LDLr表达的影响,探讨LDLr在脂质导致肾病大鼠肾脏损害过程中的作用及他汀类药物肾脏保护的机制。方法：雄性SD大鼠随机分为正常对照组、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),12周后收集标本,光镜观察肾小球硬化情况,酶比色法和油红染色法检测肾组织内胆固醇含量,RT-PCR和Western-blot技术分别检测肾组织LDLr、胆固醇调节元件结合蛋白-2(SREBP-2) mRNA和蛋白质表达。结果：模型组出现明显肾小球硬化(P<0.01),LDLr、SREBP-2 mRNA和蛋白表达明显增强(P均<0.01),肾组织内胆固醇含量明显升高(P<0.01)；线性回归分析显示肾组织LDLr、SREBP-2蛋白表达上调与肾组织胆固醇酯(CE)含量呈显著正相关性(P均<0.01)。治疗组肾小球硬化明显减轻(P<0.01),LDLr、SREBP-2 mRNA和蛋白表达、肾组织内胆固醇含量均较模型组低(分别P<0.05或P<0.01)。结论：肾病大鼠肾小球硬化过程中,肾组织内SREBP-2、LDLr表达明显上调,脂质可能通过过度表达的LDLr途径在肾组织内沉积,加重肾小球硬化；辛伐他汀可能通过下调LDLr途径,减少脂质在肾脏组织内沉积,发挥肾脏保护作用。