miRNA-223-3p在不明原因复发性流产患者绒毛组织中表达以及在血管生成中的作用

Expressions of miRNA-223-3p in villi of unexplained recurrent spontaneous abortion and the role in angiogenesis

目的探讨miRNA-223-3p在不明原因复发性流产患者绒毛组织中表达以及在血管生成中的作用及可能机制。方法选取57例不明原因复发性流产患者,其中,流产2~3次36例,≥4次21例,同期,选取正常早孕行人工流产术患者42例作为对照组,利用实时荧光定量PCR技术检测绒毛组织中miRNA-223-3p、Rps6kb1、缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)表达,免疫组化法检测绒毛组织中微血管密度(MVD)。结果不明原因复发性流产患者绒毛组织中miRNA-223-3p表达量高于对照组,而Rps6kb1 mRNA、HIF-1αmRNA和VEGF mRNA表达量均低于对照组,≥4次不明原因复发性流产患者miRNA-223-3p表达量高于2~3次和对照组,而Rps6kb1 mRNA、HIF-1αmRNA和VEGF mRNA表达量低于2~3次和对照组,均差异有统计学意义(P<0.05);免疫组化结果显示,不明原因复发性流产患者绒毛组织中MVD为(23.3±6.1)个,远低于对照组的(41.6±5.3)个,≥4次不明原因复发性流产患者绒毛组织中MVD低于2~3次,均差异有统计学意义(P<0.05);Pearson相关分析显示,不明原因复发性流产患者绒毛组织中miRNA-223-3p表达量与HIF-1αmRNA和VEGF mRNA表达量及MVD均呈负相关(r=-0.496、-0.638和-0.597,P<0.001),HIF-1αmRNA表达量与VEGF mRNA表达量和MVD均呈正相关(r=0.584、0.439,P<0.001);VEGF mRNA表达量与MVD呈正相关(r=0.600,P<0.001)。结论 miRNA-223-3p在不明原因复发性流产患者绒毛组织中表达上调,可能与Rps6kb1/HIF-1α信号通路有关。

Objective To investigate the expressions of miRNA-223-3 p in villi of unexplained recurrent spontaneous abortion and the role in angiogenesis and possible mechanisms. Methods 57 cases of unexplained recurrent spontaneous abortion were selected, among which,abortion 2 or 3 times were 36 cases and ≥4 times were 21 cases. Over the same period,42 cases of normal pregnancy induced abortion seemed as control group were selected. The expressions of miRNA-223-3 p,Rps6 kbl,HIF-1α and VEGF in villi were detected by using real-time PCR technology. The MVD in villi were tested by using immunohistochemistry. Results The expression levels of miRNA-223-3 p in villi of unexplained recurrent spontaneous abortion were higher than the control group,while the expression levels of Rps6 kbl mRNA,HIF-1α mRNA and VEGF mRNA were lower than the control group,the expression levels of miRNA-223-3 p in villi of≥4 times were higher than the 2 to 3 times and the control group,while the expression levels of Rps6 kb1 mRNA,HIF-la mRNA and VEGF mRNA were lower than the 2 or 3 times and the control group, the differences were statistically significant(P < 0.05). Immunohistochemistry results showed that the MVD in villi of unexplained recurrent spontaneous abortion patients was(23. 3 ±6. 1),which was much lower than the control group,which was(41.6 ±5.3),the MVD in villi of ≥4 times of unexplained recurrent spontaneous abortion was less than 2 or 3 times,the differences were statistically significant(P <0.05). Pearson correlation analysis showed that the expression levels of miRNA-223-3 p in villi of unexplained recurrent spontaneous abortion were negatively correlated with the expression levels of HIF-1α mRNA and VEGF mRNA(r=-0.496,-0.638 and-0.597,P<0.001),the expression levels of HIF-1α mRNA were positively correlated with the expression levels of VEGF mRNA and MVD(r=0.584 and 0.439, P < 0.001), and the expression levels of VEGF mRNA was positively correlated with MVD( r = 0. 600,P < 0.001). Conclusion The expression of miRNA-223-3 p was upregulated in villi of unexplained recurrent spontaneous abortion. It might be related with the Rps6 kb1/HIF-1α signaling pathway.