化疗性卵巢功能早衰动物模型及患者血清miR-21水平的变化

Changes of serum miR-21 level in animal model and patients with chemotherapy-induced premature ovarian failure

目的检测化疗性卵巢功能早衰(CIPOF)大鼠动物模型及患者血清micro RNA-21(mi R-21)的水平,探讨mi R-21与CIPOF的发生是否存在相关性。方法采用腹腔注射环磷酰胺建立CIPOF动物模型,在建模后第1、15天尾静脉采血,QT-PCR法检测血清mi R-21水平,同时检测雌二醇(E2)及卵泡刺激素(FSH)水平、卵巢结构,并行相关性分析。收集2014年1月-2015年6月就诊的CIPOF患者30例,以及健康体检的育龄女性30例作为对照,检测血清mi R-21水平,同时与其他检测指标[黄体生成素(LH)、E2、FSH、泌乳素(PRL)]进行相关性分析。结果 CIPOF动物模型及患者血清mi R-21水平分别较对照组明显降低,差异有统计学意义(t=15.467,P=0.000;t=10.197,P=0.000)。动物模型中mi R-21分别与E2,始基、初级、次级及窦状卵泡数目呈正相关(r=0.750,P=0.000;r=0.403,P=0.006;r=0.704,P=0.000;r=0.783,P=0.000;r=0.849,P=0.000),与FSH呈负相关(r=–0.801,P=0.000)。临床患者中mi R-21与E2呈正相关(r=0.817,P=0.000),与FSH、LH呈负相关(r=–0.771,P=0.000;r=–0.784,P=0.000),与PRL无相关性(r=0.204,P=0.207)。结论在CIPOF动物模型及患者血清中mi R-21水平降低,与卵巢功能下降呈正相关,提示mi R-21可能参与CIPOF的发病过程,有望成为防治CIPOF的新靶点。

Objective To investigate the correlation between miR-21 and chemotherapy-induced premature ovarian failure （CIPOF） by measuring the serum miR-21 level in animal models and patients. Methods CIPOF animal model was established by intraperitoneal injection of cyclophosphamide. Caudal vein blood samples were collected at the first and the 15th day after the models established. Serum miR-21 level was detected by QT-PCR. The correlations between miR-21 level with estradiol （E2） level, follicle-stimulating hormone （FSH） level and ovary structure were analyzed. From Jan. 2014 to Jun. 2015, 30 patients with CIPOF and 30 normal women of child-bearing age were enrolled in the study. Serum miR-21 levels of all cases were detected and the correlations between serum miR-21 levels and other laboratory indexes [luteinizing hormone （LH）, E2, FSH and prolactin （PRL）] were analyzed. Results Compared to control group, the serum miR-21 levels in CIPOF animal models and patients were obviously lower with statistical significances （t=15.467, P=0.000; t=10.197, P=0.000）. Positive correlations existed in animal models between miR-21 and Ez, primordial, primar）5 secondary and antrum follicle numbers （r=0.750, P=0.000; r=0.403, P=0.006; r=0.704, P=0.000; r=0.783, P=0.000; r=0.849, P=0.000, respectively）, and a negative correlation existed between miR-21 and FSH （r=-0.801, P=0.000）. A positive correlation existed in patients between miR-21 and E2 （r=0.817, P=0.000）, and negative correlations existed between miR-21 and FSH （r=-0.771, P=0.000） and miR-21 and LH （r=-0.784, P=0.000）. No correlation existed between miR- 21 and PILL （r=0.204, P=0.207）. Conclusion The evident decrease of serum miR-21 level in CIPOF animal models and patients suggests that miR-21 may play an important role in the process of CIPOF, and the miR-21 may be a potential prevention and therapeutic option for CIPOF.