子宫腺肌病组织及原代细胞中PARP-1、HIF-1α的表达及临床意义

doi:10.6040/j.issn.1671-7554.0.2021.0472

摘要/Abstract

摘要： 目的探讨聚腺苷二磷酸核糖聚合酶-1(PARP-1)、缺氧诱导因子-1α(HIF-1α)在子宫腺肌病(AM)组织中及原代内膜间质细胞中的表达及临床意义。方法利用免疫组织化学法检测PARP-1及HIF-1α在AM在位、异位内膜组织腺体中的表达并分析其相关性;提取原代细胞, PARP-1抑制剂处理后利用Western blotting测定PARP-1表达降低对HIF-1α表达量的影响。结果免疫组织化学结果显示,PARP-1在AM在位(26/31 vs 4/10,P=0.006)及异位(24/31 vs 4/10, P=0.027)内膜组织中的表达量增高,差异有统计学意义;HIF-1α在AM在位(24/31 vs 3/10, P=0.006)及异位(23/31 vs 3/10, P=0.012)内膜组织中的表达量增高,差异有统计学意义;二者表达量呈中度正相关(AM在位内膜中r=0.357,P=0.038;AM异位内膜中r=0.519,P=0.002),但PARP-1(P=0.052)、HIF-1α(P=0.767)在AM在位及异位内膜腺体组织中的表达差异均无统计学意义。Western blotting结果显示,PARP-1在AM异位内膜间质细胞中的表达量(1.016±0.051)高于在位内膜间质细胞(0.869±0.144),差异有统计学意义(P=0.025),且AM内膜间质细胞中PARP-1的表达量均较正常子宫内膜间质细胞增高(P<0.001),3组数据满足方差齐性(Levence=3.196,P=0.065)。使用PARP-1抑制剂后,PARP-1在正常子宫内膜(t=5.740,P=0.001)、AM在位子宫内膜(t=4.786,P=0.003)、异位子宫内膜(t=9.458,P<0.001)中的表达量均降低,且以AM异位内膜间质细胞降低最为明显。HIF-1α在AM在位及异位内膜间质细胞中的表达差异无统计学意义(P=0.896),而AM内膜间质细胞(P<0.001)中的表达量均高于正常子宫内膜间质细胞中的表达,3组数据符合方差齐性(Levence=2.233,P=0.150)。使用PARP-1抑制剂降低PARP-1的表达后,HIF-1α在正常子宫内膜(t=4.2215,P=0.014)、AM在位内膜(t=15.768,P<0.001)、异位内膜细胞(t=3.459,P=0.025)3组间质细胞中的表达量均较前降低。结论 PARP-1和HIF-1α在AM组织及细胞中高表达,且 PARP-1表达量的变化可能影响HIF-1α的表达。

关键词: 子宫腺肌病, 聚腺苷二磷酸核糖聚合酶-1, 缺氧诱导因子-1α, 聚腺苷二磷酸核糖聚合酶-1抑制剂, 在位、异位子宫内膜

Abstract: Objective To explore the expressions and significance of poly(ADP-ribose)polymerase-1(PARP-1)and hypoxia inducible factor-1(HIF-1α)in adenomyosis(AM)tissues and normal endometrial tissues. Methods The expressions of PARP-1 and HIF-1α in the eutopic and ectopic endometria of women with AM and in normal endometria were detected with immunohistochemistry. The primary interstitial cells were extracted from the eutopic and ectopic endometria of patients with AM. After the expression of PARP-1 was knocked down, the change of HIF-1α expression was measured. Results Immunohistochemistry results showed that the expression of PARP-1 was higher in the eutopic(26/31 vs 4/10, P=0.006)and ectopic(24/31 vs 4/10, P=0.027)endometria of AM than in normal endometria; the expression of HIF-1α was higher in the eutopic(24/31 vs 3/10, P=0.006)and ectopic(23/31 vs 3/10, P=0.012)endometria of AM than in normal endometria. There was a positive correlation(r=0.357, P=0.038 in eutopic endometrial tissues; r=0.519, P=0.002 in ectopic endometrial tissues)between expressions of PARP-1 and HIF-1α, but there was no significant difference in the expressions of PARP-1(P=0.052)and HIF-1α(P=0.767)in the eutopic and ectopic endometria of adenomyosis. Western blotting results showed that the expression of PARP-1 in ectopic endometrial interstitial cells of AM was higher than that in eutopic endometrial interstitial cells(P=0.025), and PARP-1 was highly expressed in eutopic(P<0.001)and ectopic(P<0.001)endometrial interstitial cells of AM compared with normal endometrial interstitial cells. After PARP-1 knockdown, the expressionin eutopic endometria(t=4.786, P=0.003), ectopic endometria(t=9.458, P<0.001), and normal endometria(t=5.740, P=0.001)was significantly reduced, and the reduction of ectopic endometrial interstitial cells in AM was the most obvious. There was no significant difference in the expression of HIF-1α in eutopic and ectopic endometrial interstitial cells of AM(P=0.896), and the expression of HIF-1α in eutopic endometrial stromal cells(P<0.001)and ectopic endometrial stromal cells(P<0.001)was higher than that in normal endometrium interstitial cells. After PARP-1 knockdown, the expression of HIF-1α in eutopic endometria of AM(t=15.768, P<0.001), ectopic endometrial cells(t=3.459, P=0.025), and normal endometria(t=4.221 5, P=0.014)was significantly lower than before. Conclusion Both PARP-1 and HIF-1α may be involved in the development of AM, and the expression of PARP-1 may affect the expression of HIF-1α.

Key words: Adenomyosis, Poly(ADP-ribose)polymerase-1, Hypoxia inducible factor-1α, Poly(ADP-ribose)polymerase-1 inhibitor, Eutopic and ectopic endometria

中图分类号:

R711.71

徐歌,李青,张灿灿,田永杰. 子宫腺肌病组织及原代细胞中PARP-1、HIF-1α的表达及临床意义[J]. 山东大学学报 (医学版), 2022, 60(4): 55-61.

XU Ge, LI Qing, ZHANG Cancan, TIAN Yongjie. Expressions and clinical significance of PARP-1 and HIF-1α in adenomyosis tissues and primary cells[J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 55-61.

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