目的观察microRNA(miRNA)在单侧输尿管梗阻(UUO)大鼠模型中的表达,筛选与肾间质纤维化(RIF)相关的miRNA。方法将48只SD大鼠分为UUO组和假手术组(Sham组),时间点为术后3d、7d、14d。Masson染色观察肾脏病理。茎环实时定量PCR检测48条miRNA在肾组织的表达。结果术后第3天,UUO组可见灶状肾间质水肿和单个核细胞浸润;术后第7天,灶状间质纤维化;术后第14天,显著间质纤维化。Sham组肾脏未见明显病变。相对于Sham组,UUO组在术后3d、7d和14d分别有25条、24条和2l条miRNA的表达差异有统计学意义(均P〈0.05)。其中有5条miRNA(miR.132、miR-192、miR-194、miR-29c和miR-203)在术后3、7和14d一致上调或下调,且与肾小管间质病变程度相关(均P〈0.05)。结论在大鼠UUO模型的RIF过程中20多条miRNA存在差异表达,提示miRNA可能参与RIF的发生发展过程。miR-132、miR.192、miR.194、miR-29c和miR.203与大鼠RIF关系密切,值得进一步研究。
Objective To investigate the expression pattern of microRNA (miRNA) in the kidneys of unilateral ureteral obstruction (UUO) rats and to identify specific miRNA related to renal interstitial fibrosis (RIF). Methods Forty-eight male SD rats were divided into two groups: UUO group and sham-operated (Sham) group. Rats were sacrificed at 3, 7 and 14 days after operation. Histologic changes were examined by Masson staining. Forty-eight selected miRNAs were examined by stem-loop real-time qPCR. Results At the 3rd day after operation, obstructed kidneys from operation rats showed mild edema in the interstitium and mononuclear cell infiltration. At the 7th day after operation, focal interstitial fibrosis was observed. At the 14th day after operation, fibrosis became more severe. The Sham kidneys showed no pathological changes. At the 3th day after operation, 25 miRNAs were differentially expressed. At the 7th day after operation, 24 miRNAs were aberrantly expressed, whereas 21 miRNAs were differentially expressed at the 14th day after operation (P〈0.05). Among these miRNAs, miR-132, miR-192, miR-194, miR-29c and miR-203 were consistently up-regulated or down-regulated in a time-dependent manner after operation. There were significantly correlations between the expression of five miRNAs and severity of tubulointerstitial injury (P〈0.05). Conclusions There are at least 20 miRNAs differentiallyexpressed in the process of RIF induced by UUO. There are significantly correlations between the expression of miR-132, miR-192, miR-194, miR-29c and miR-203 and the severity of tubulointerstitial injury. They may be closely related to RIF. A further study is needed.