Huang Y, Zeng C, Wu P L, Zhou Y, Peng C, Xue Q, Zhou Y F
Department of Obstetric and Gynecology, Peking University First Hospital, Beijing 100034, China.
Zhonghua Fu Chan Ke Za Zhi. 2019 May 25;54(5):324-329. doi: 10.3760/cma.j.issn.0529-567x.2019.05.007.
To compare the expression of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in tissue and fluid samples from patients with endometriosis, and investigate whether LIF and IL-6 regulate VEGF in human endometriotic stromal cells (ESC). The levels of VEGF, LIF, IL-6 in serum, peritoneal fluid of patients with and without endometriosis were measured by ELISA. The mRNA of these three factors in the ectopic and eutopic endometrial tissue and stromal cells were measured by real-time PCR. ESC derived from ovarian endometriomas were cultured using the method of primary cell culture with LIF and IL-6, and the level of VEGF mRNA and protein were measured by the method of real-time PCR and ELISA respectively. VEGF and IL-6 concentration were 1.2 and 1.3 times higher in the serum of patients with endometriosis than in the control group [(94±19) versus (78±17) ng/L; (45±14) versus (35±9) ng/L; all 0.05]. VEGF and IL-6 concentration were 1.2 and 1.4 times higher in the peritoneal fluid of patients with endometriosis than in the control group [(110±25) versus (91±21) ng/L; (69±20) versus (49±15) ng/L; all 0.05]. VEGF and IL-6 concentrations in peritoneal fluid of patients with endometriosis were 1.2 and 1.5 times higher than in serum (all 0.01). VEGF, LIF and IL-6 mRNA expression were 2.2, 8.6, 44.7 times higher in ESC compared with the matching eutopic endometrial stromal cells (all 0.01). LIF and IL-6 mRNA were 2.0 and 64.8 times higher in ectopic endometrial tissue than the matching eutopic endometrial tissue (all 0.05).ESC cultured with LIF, IL-6 and LIF+IL-6 induce VEGF protein secretion [(106±18), (124±30), (140±27) ng/L] by 1.3, 1.5 and 1.7 times (all 0.05). Overexpression of LIF and IL-6 may synergistically contribute to upregulation of VEGF in ESC and promote development of endometriosis.
比较子宫内膜异位症患者组织和体液样本中白血病抑制因子(LIF)、白细胞介素-6(IL-6)和血管内皮生长因子(VEGF)的表达,并研究LIF和IL-6是否在人子宫内膜异位症基质细胞(ESC)中调节VEGF。采用酶联免疫吸附测定法(ELISA)检测有或无子宫内膜异位症患者血清、腹腔液中VEGF、LIF、IL-6的水平。采用实时荧光定量聚合酶链反应(real-time PCR)检测异位和在位子宫内膜组织及基质细胞中这三种因子的mRNA。采用原代细胞培养方法培养来源于卵巢子宫内膜异位囊肿的ESC,分别用实时荧光定量聚合酶链反应和ELISA法检测VEGF mRNA和蛋白水平。子宫内膜异位症患者血清中VEGF和IL-6浓度分别比对照组高1.2倍和1.3倍[(94±19)对(78±17)ng/L;(45±14)对(35±9)ng/L;均P<0.05]。子宫内膜异位症患者腹腔液中VEGF和IL-6浓度分别比对照组高1.2倍和1.4倍[(110±25)对(91±21)ng/L;(69±20)对(49±15)ng/L;均P<0.05]。子宫内膜异位症患者腹腔液中VEGF和IL-6浓度分别比血清高1.2倍和1.5倍(均P<0.01)。与配对的在位子宫内膜基质细胞相比,ESC中VEGF、LIF和IL-6 mRNA表达分别高2.2倍、8.6倍、44.7倍(均P<0.01)。异位子宫内膜组织中LIF和IL-6 mRNA分别比配对的在位子宫内膜组织高2.0倍和64.8倍(均P<0.05)。用LIF、IL-6和LIF+IL-6培养的ESC诱导VEGF蛋白分泌[(106±18)、(124±30)、(140±27)ng/L]分别增加1.3倍、1.5倍和1.7倍(均P<0.05)。LIF和IL-6的过表达可能协同促进ESC中VEGF的上调并促进子宫内膜异位症的发展。