目的探究糖尿病肾病(DN)患者血清miR-488,miR-654水平与疾病严重程度及预后的关系。方法选取92例2022年1月~2024年1月雅安市人民医院诊治的DN患者(DN组)以及60例健康正常人(健康组)进行miR-488,miR-654水平检测,Pearson分析血清miR-488...目的探究糖尿病肾病(DN)患者血清miR-488,miR-654水平与疾病严重程度及预后的关系。方法选取92例2022年1月~2024年1月雅安市人民医院诊治的DN患者(DN组)以及60例健康正常人(健康组)进行miR-488,miR-654水平检测,Pearson分析血清miR-488与miR-654的相关性;卡方检验分析血清miR-488,miR-654表达水平与临床病理特征和肾脏损伤程度的关系;ROC预测DN患者预后情况。结果DN患者与健康组相比,血清miR-488(1.71±0.40 vs 1.08±0.15)表达水平明显升高,miR-654(0.66±0.19 vs 0.94±0.22)表达水平明显降低,差异具有统计学意义(t=11.666,8.340,均P<0.05)。糖尿病年限≥10年、24h尿蛋白≥3 g/L、血肌酐≥150μmol/L、肾小球滤过率<60 ml/min/1.73m2,血尿素氮≥7.5mmol/L的DN患者血清miR-488高表达、miR-654低表达占比显著高于血清miR-488低表达、miR-654高表达患者,差异具有统计学意义(χ^(2)=5.283~25.234;4.356~8.587,均P<0.05)。Pearson分析DN组血清miR-488与miR-654呈负相关(r=-0.405,P<0.05);血清miR-488与24h尿蛋白、血肌酐、血尿素氮呈正相关(r=0.376,0.435,0.406,均P<0.05),与肾小球滤过率呈负相关(r=-0.382,P<0.05);血清miR-654与24h尿蛋白、血肌酐、血尿素氮呈负相关(r=-0.418,-0.367,-0.425,均P<0.05),与肾小球滤过率呈正相关(r=0.374,P<0.05)。肾小球分级Ⅳ级、间质炎症2分、间质纤维化和肾小管萎缩(IFTA)3分DN患者miR-488高表达、miR-654低表达占比显著高于miR-488低表达、miR-654高表达,差异具有统计学意义(χ^(2)=7.916~20.669,8.432~13.258,均P<0.05)。与预后不良组相比,预后良好组血清miR-488表达水平显著降低(1.57±0.29 vs 1.89±0.17),miR-654表达水平显著升高(0.78±0.21 vs 0.51±0.19),差异具有统计学意义(t=6.202,6.369,均P<0.05)。血清miR-488,miR-654单独及二者联合对DN患者预后的敏感度分别为87.50%,80.00%和90.00%,特异度分别为84.62%,86.54%和82.69%,AUC(95%CI)分别为0.838(0.748~0.927),0.824(0.731~0.916)和0.906(0.846~0.966),二者联合预测优于各自单独预测(Z=2.225,2.033,P=0.026,0.042)。结论DN患者肾脏损伤程度越低,血清miR-488表达水平越低,血清miR-654越高,血清miR-488,miR-654可用于对DN患者病情及预后预测,联合预测优于单独预测。展开更多
Circular RNAs(circRNAs)are a class of conserved,endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation and are highly enriched in the nervous system.They participate i...Circular RNAs(circRNAs)are a class of conserved,endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation and are highly enriched in the nervous system.They participate in the survival and differentiation of multiple nerve cells,and may even promote the recovery of neurological function after stroke.However,their role in the inflammatory response after spinal cord injury remains unclear.In the present study,we established a mouse model of T9 spinal cord injury using the modified Allen’s impact method,and identified 16,013 circRNAs and 960 miRNAs that were differentially expressed after spinal cord injury.Of these,the expression levels of circPrkcsh were significantly different between injured and sham-treated mice.We then treated astrocytes with tumor necrosis factor-αin vitro to simulate the inflammatory response after spinal cord injury.Our results revealed an elevated expression of circPrkcsh with a concurrent decrease in miR-488 expression in injured cells.We also found that circPrkcsh regulated the expression of the inflammationrelated gene Ccl2.Furthermore,in tumor necrosis factor-α-treated astrocytes,circPrkcsh knockdown decreased the expression of Ccl2 by upregulating miR-488 expression,and reduced the secretion of inflammatory cytokines in vitro.These findings suggest that differentially expressed circRNAs participate in the inflammatory response after spinal cord injury and act as the regulators of certain microRNAs.Furthermore,circPrkcsh may be used as an miR-488 sponge to regulate Ccl2 expression,which might provide a new potential therapy for SCI.The study was approved by the Animal Ethics Committee of Shandong University of China(approval No.KYLL-20170303)on March 3,2017.展开更多
文摘目的探究糖尿病肾病(DN)患者血清miR-488,miR-654水平与疾病严重程度及预后的关系。方法选取92例2022年1月~2024年1月雅安市人民医院诊治的DN患者(DN组)以及60例健康正常人(健康组)进行miR-488,miR-654水平检测,Pearson分析血清miR-488与miR-654的相关性;卡方检验分析血清miR-488,miR-654表达水平与临床病理特征和肾脏损伤程度的关系;ROC预测DN患者预后情况。结果DN患者与健康组相比,血清miR-488(1.71±0.40 vs 1.08±0.15)表达水平明显升高,miR-654(0.66±0.19 vs 0.94±0.22)表达水平明显降低,差异具有统计学意义(t=11.666,8.340,均P<0.05)。糖尿病年限≥10年、24h尿蛋白≥3 g/L、血肌酐≥150μmol/L、肾小球滤过率<60 ml/min/1.73m2,血尿素氮≥7.5mmol/L的DN患者血清miR-488高表达、miR-654低表达占比显著高于血清miR-488低表达、miR-654高表达患者,差异具有统计学意义(χ^(2)=5.283~25.234;4.356~8.587,均P<0.05)。Pearson分析DN组血清miR-488与miR-654呈负相关(r=-0.405,P<0.05);血清miR-488与24h尿蛋白、血肌酐、血尿素氮呈正相关(r=0.376,0.435,0.406,均P<0.05),与肾小球滤过率呈负相关(r=-0.382,P<0.05);血清miR-654与24h尿蛋白、血肌酐、血尿素氮呈负相关(r=-0.418,-0.367,-0.425,均P<0.05),与肾小球滤过率呈正相关(r=0.374,P<0.05)。肾小球分级Ⅳ级、间质炎症2分、间质纤维化和肾小管萎缩(IFTA)3分DN患者miR-488高表达、miR-654低表达占比显著高于miR-488低表达、miR-654高表达,差异具有统计学意义(χ^(2)=7.916~20.669,8.432~13.258,均P<0.05)。与预后不良组相比,预后良好组血清miR-488表达水平显著降低(1.57±0.29 vs 1.89±0.17),miR-654表达水平显著升高(0.78±0.21 vs 0.51±0.19),差异具有统计学意义(t=6.202,6.369,均P<0.05)。血清miR-488,miR-654单独及二者联合对DN患者预后的敏感度分别为87.50%,80.00%和90.00%,特异度分别为84.62%,86.54%和82.69%,AUC(95%CI)分别为0.838(0.748~0.927),0.824(0.731~0.916)和0.906(0.846~0.966),二者联合预测优于各自单独预测(Z=2.225,2.033,P=0.026,0.042)。结论DN患者肾脏损伤程度越低,血清miR-488表达水平越低,血清miR-654越高,血清miR-488,miR-654可用于对DN患者病情及预后预测,联合预测优于单独预测。
基金supported by the National Natural Science Foundation of China,Nos.81771346,82071383the Taishan Scholar Program of Shandong Province of China,No.tsqn201812156+1 种基金Spring City Leader Talent Support Plan,No.201984Rongxiang Regenerative Medicine Foundation of Shandong University,No.2019SDRX-23(all to BN)。
文摘Circular RNAs(circRNAs)are a class of conserved,endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation and are highly enriched in the nervous system.They participate in the survival and differentiation of multiple nerve cells,and may even promote the recovery of neurological function after stroke.However,their role in the inflammatory response after spinal cord injury remains unclear.In the present study,we established a mouse model of T9 spinal cord injury using the modified Allen’s impact method,and identified 16,013 circRNAs and 960 miRNAs that were differentially expressed after spinal cord injury.Of these,the expression levels of circPrkcsh were significantly different between injured and sham-treated mice.We then treated astrocytes with tumor necrosis factor-αin vitro to simulate the inflammatory response after spinal cord injury.Our results revealed an elevated expression of circPrkcsh with a concurrent decrease in miR-488 expression in injured cells.We also found that circPrkcsh regulated the expression of the inflammationrelated gene Ccl2.Furthermore,in tumor necrosis factor-α-treated astrocytes,circPrkcsh knockdown decreased the expression of Ccl2 by upregulating miR-488 expression,and reduced the secretion of inflammatory cytokines in vitro.These findings suggest that differentially expressed circRNAs participate in the inflammatory response after spinal cord injury and act as the regulators of certain microRNAs.Furthermore,circPrkcsh may be used as an miR-488 sponge to regulate Ccl2 expression,which might provide a new potential therapy for SCI.The study was approved by the Animal Ethics Committee of Shandong University of China(approval No.KYLL-20170303)on March 3,2017.