miR-455在原因不明复发性流产病人绒毛组织中表达及意义

目的 探讨miR-455在原因不明复发性流产(URSA)病人绒毛组织中表达及意义.方法 72例URSA病人根据自然流产次数分为2~3次者(n=45)和≥4次者(n=27),同期,选取要求终止妊娠的正常早孕者40例作为对照组,留取绒毛组织,利用实时荧光定量PCR技术检测绒毛组织中miR-455、血管内皮生长因子(VEGF)和可溶性血管内皮生长因子受体-1(sFlt-1)基因表达,免疫组化SP法检测绒毛组织中微血管密度(MVD).结果 URSA病人绒毛组织中miR-455和sFlt-1 mRNA表达量均高于对照组,而VEGF mRNA表达量低于对照组,URSA中2~3次者miR-455和sFlt-1 mRNA表达量均低于≥4次者,而VEGF mRNA表达量高于≥4次者,均差异有统计学意义(P<0.05);免疫组化结果显示,URSA病人绒毛组织中MVD为(9.9±3.2)条,低于对照组的(21.5±3.8)条,URSA中2~3次者绒毛组织中MVD为(13.4±3.1)条,高于≥4次者的(7.2±2.4)条,均差异有统计学意义(P<0.05);Pearson相关分析显示,URSA病人绒毛组织中miR-455表达量与VEGF mRNA表达量和MVD均呈负相关(r=-0.452、-0.433,P<0.05),而与sFlt-1 mRNA表达量呈正相关(r=0.539,P<0.05).结论 miR-455在URSA病人绒毛组织中呈高表达,且与sFlt-1表达呈正相关,与VEGF表达和MVD均呈负相关,提示可能通过促进sFlt-1表达而抑制VEGF信号通路活性,从而抑制绒毛组织中血管新生.

Expression and significance of miR-455 in villi tissues of patients with unexplained recurrent spontaneous abortion

Objective To investigate the expression and significance of miR-455 in villi tissues of patients with unexplained recurrent spontaneous abortion(URSA).Methods 72 cases of URSA patients were divided into 2 or 3 times(n=45) group and ≥4 times(n=27) group according to the natural frequency of abortion.Over the same period,40 cases of the normal pregnancy of terminate were selected as the control group.The expressions of miR-455,VEGF and sFlt-1 genes in villi tissues were detected by real-time PCR technology.The MVD in villi tissues was tested by immunohistochemical SP method.Results The expression levels of miR-455 and sFlt-1 mRNA in villus tissues of URSA patients were higher than the control group,while the expression levels of VEGF mRNA were lower than the control group.The expression levels of miR-455 and sFlt-1 mRNA in villus tissues of 2 to 3 times URSA patients were lower than the≥4 times,while the expression levels of VEGF mRNA were higher than the ≥4 times.The differences were statistically significant(P<0.05).The results of immunohistochemistry showed that the MVD in villi tissues of URSA patients was(9.9±3.2),which was lower than(21.5±3.8) in the control group.The MVD of 2 to 3 times URSA patients was(13.4±3.1),which was higher than(7.2±2.4) in the ≥4 times.The differences were statistically significant(P<0.05).Pearson correlation analysis showed that the expression levels of miR-455 in villi tissues of URSA patients were negatively correlated with the expression levels of VEGF mRNA and MVD(r=-0.452 and-0.433,P<0.05),and were positively correlated with the expression levels of sFlt-1 mRNA(r=0.539,P<0.05).Conclusion miR-455 was highly expressed in villus tissues of URSA patients,and was positive correlated with the expression of sFlt-1while negatively correlated with the expressions of VEGF and MVD.Suggestingthat it may inhibit the VEGF signaling pathway activity by promotings sFlt-1 expression,thereby inhibiting angiogenesis in villi tissues.