基质金属蛋白酶及其抑制剂在异常出血子宫内膜中的表达

Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase in endometrium of abnormal uterine bleeding

目的分析子宫异常出血(AUB)患者子宫内膜中前基质金属蛋白酶2(proMMP-2)、MMP-2、基质金属蛋白酶组织抑制因子1(TIMP-1)的表达及其与性激素浓度的关系。方法收集2015年1月1日至2017年12月31日在陕西省西北妇女儿童医院与子长县妇幼保健院就诊的健康妇女和AUB患者的子宫内膜标本,标本组织由病理学专家在显微镜下评估。用明胶酶谱法检测proMMP-2、MMP-2蛋白表达水平,逆向酶谱法检测TIMP-1蛋白水平,线性回归分析其表达与组织病理学诊断及性激素浓度的相关性。结果病例组子宫内膜proMMP-2的表达与雌激素、孕激素水平、内分泌功能障碍的发生相关(P<0.05)。病例组MMP-2的表达与雌激素、孕激素水平无相关性(P>0.05),但与子宫内膜息肉、内分泌功能障碍、子宫内膜增生的发生相关(P<0.05)。病例组TIMP-1的表达与激素浓度无相关性。结论AUB患者的proMMP-2表达量低于健康女性。随着出血时间的延长,AUB患者的MMP-2表达增加,此时雌激素促进proMMP-2的表达上调,但孕激素使其表达下调。

Objective To analyze the expression of pro-matrix metalloproteinase 2(proMMP-2),MMP-2 and tissue inhibitor of matrix metalloproteinase-1(TIMP-1)in endometrium of patients with abnormal uterine bleeding(AUB)and their relationship with sex hormone concentration.Methods Endometrial specimens of healthy women and AUB patients were collected from 1 January 2015 to 31 December 2017 in Northwest Women's and Children's Hospital and Zichang County Maternal and Child Health Care Hospital.The specimens were evaluated by pathologists under a microscope.The expression levels of proMMP-2 and MMP-2 protein were detected by gelatin zymography and TIMP-1 protein by reverse zymography;linear regression analysis was used to analyze the correlation between its expression and histopathological diagnosis and sex hormone concentration.Results The expression of proMMP-2 in the endometrium of the case group was correlated with the levels of estrogen,progesterone and the occurrence of endocrine dysfunction(P<0.05).The expression of MMP-2 in the case group was not correlated with the levels of estrogen and progesterone(P>0.05),but it was correlated with the occurrence of endometrial polyps,endocrine dysfunction and endometrial hyperplasia(P<0.05).The expression of TIMP-1 in the case group was not related to hormone concentration.Conclusion The expression of proMMP-2 in AUB patients was lower than that in healthy women.With the prolongation of bleeding time,the expression of MMP-2 in AUB patients increased,while the expression of proMMP-2 was up-regulated by estrogen,but down-regulated by progesterone.