新月体型肾小球肾炎中肝X受体α的表达及意义

Increased expression of liver X receptor α protein in renal tubular epithelial cells of crescentic glomerulonephritis

目的探讨肝X受体α(LXRα)在大鼠新月体型肾小球肾炎(GN)的表达及意义。方法 7周龄Wistar Kyoto雄性大鼠40只随机分为两组。其中20只静脉注射兔抗大鼠肾小球基底膜抗体构建新月体型肾小球肾炎模型,20只作为正常对照。于注射抗体后第3、7、14、28和49天分别测定24h尿蛋白;免疫组织化学法检测第3、14、28和49天肾炎组和对照组大鼠肾组织LXRα表达;Western blotting和实时定量PCR检测第14天肾炎肾皮质LXRα蛋白和mRNA表达变化。结果注射抗体后第14天尿蛋白达(167.03±42.50)mg/24h;新月体百分比达65%;肾炎大鼠肾小管上皮细胞核LXRα表达明显增加;肾炎组肾皮质LXRα蛋白表达明显高于同期对照组,但肾皮质mRNA表达则未见上调。结论新月体型肾炎肾小管上皮细胞核LXRα蛋白表达增强,说明肾小管LXR通路参与此型肾炎的发病过程。

Objective To observe the change of expression of liver X receptorα（LXRα） protein and mRNA in crescentic glomelonephritis（GN）. Methods Fourty male Wistar Kyoto rats were randomly divided into control group and GN group. Crescentic GN was induced by once intravenous injecting of rabbit anti-rat glomerular basement membrane（GBM） antibody in 20 rats as GN group. Proteinuria/24 hours were measured on days 3,7, 14, 28 and 49. Expression of LXRα protein in the kidney on days 3, 14, 28 and 49 was detected by immunohistochemistry, and LXRα protein and mRNA in renal cortex on day 14 were analysed by Western blotting and reverse transcription real time polymerse chain reaction （Real time-PCR）. Results On days 14 after injection of GBM, crescent formation arrived 65% , and GN rats showed massive proteinuria（167.03±42.50）mg/24hours and marked lipid accumulation in renal tubular epithelial cells. There was extensive expression of LXRα protein in renal tubular epithelial cells of GN rats on day 14. No positive expression of LXRα protein was observed in macrophages and glomerular cells including mesangial cells, podocytes and endothelial cells. The expression of LXRα protein was up-regulated in renal cortex of GN rats on day 14 than that of normal rats. There was no significant difference of the LXRα mRNA level between two groups. Conclusion We provided for the first time the evidence that expression of LXRα protein in renal tubular epithelial cells of crescentic GN was increased. This finding suggests that LXR signaling pathway may be involved in the pathophysiologic process of this GN.