异位子宫内膜间质细胞中LIF及IL-6对VEGF的调控作用  

Vascular endothelial growth factor is up-regulated by leukemia inhibitory factor and interleukin-6 in human endometriotic stromal cells

作　　者：黄艳[1] 曾诚[1] 吴培莉[1] 周妍[1] 彭超[1] 薛晴[1] 周应芳[1] Huang Yan;Zeng Cheng;Wu Peili;Zhou Yan;Peng Chao;Xue Qing;Zhou Yingfang(Department of Obstetric and Gynecology, Peking University First Hospital, Beijing 100034, China)

机构地区：[1]北京大学第一医院妇产科,100034

出　　处：《中华妇产科杂志》2019年第5期324-329,共6页Chinese Journal of Obstetrics and Gynecology

基　　金：生殖健康及重大出生缺陷防控研究重点专项基金(2017YFC1001200).

摘　　要：目的检测白血病抑制因子(LIF)、白细胞介素6(IL-6)、血管内皮生长因子(VEGF)在子宫内膜异位症(内异症)患者血液、腹腔液、异位子宫内膜间质细胞及异位内膜组织中的表达,观察LIF、IL-6在异位子宫内膜间质细胞中对VEGF的调控作用。方法选择2014年11月至2015年2月在北京大学第一医院行腹腔镜手术的患者,以27例内异症患者为内异症组,以同期10例因卵巢畸胎瘤、卵巢浆液性囊腺瘤或子宫肌瘤而行腹腔镜手术的非内异症患者为对照组。使用ELISA方法测定内异症组及对照组患者血清、腹腔液中VEGF、LIF、IL-6的水平;通过实时PCR技术测定配对的异位内膜和在位内膜组织中、异位子宫内膜间质细胞和在位子宫内膜间质细胞中VEGF、LIF、IL-6 mRNA的表达;在原代培养的异位子宫内膜间质细胞中,予LIF、IL-6单独及联合处理后检测VEGF mRNA和蛋白的变化。结果内异症组患者血清中VEGF及IL-6的水平[分别为(94±19)、(45±14)ng/L]较对照组[分别为(78±17)、(35±9)ng/L]分别升高1.2倍和1.3倍(P均<0.05),内异症组患者腹腔液中VEGF及IL-6的水平[分别为(110±25)、(69±20)ng/L]较对照组[分别为(91±21)、(49±15)ng/L]分别升高1.2倍和1.4倍(P均<0.05),内异症组患者腹腔液中VEGF及IL-6的水平较血清中分别高1.2倍和1.5倍(P均<0.01)。异位子宫内膜间质细胞中VEGF、LIF及IL-6 mRNA的表达水平较自身对照的在位子宫内膜间质细胞分别高2.2、8.6、44.7倍(P均<0.01);在异位内膜组织中LIF及IL-6 mRNA的表达水平较自身配对的在位内膜组织分别高2.0和64.8倍(P均<0.05)。异位子宫内膜间质细胞予LIF、IL-6及LIF+IL-6处理后,VEGF的水平[分别为(106±18)、(124±30)、(140±27)ng/L]较空白对照细胞[(82±15)ng/L]分别升高1.3、1.5及1.7倍(P均<0.05)。结论LIF及IL-6可能协同作用于异位子宫内膜间质细胞,促进VEGF的分泌,可能在内异症的发病及疾病进展中起重要作用。Objective 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). Methods 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. Results 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 P<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 P<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 P<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 P<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 P<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 P<0.05). Conclusion Overexpression of LIF and IL-6 may synergistically contribute to upregulation of VEGF in ESC and promote development of endometriosis.

关 键 词：子宫内膜异位症 子宫内膜 间质细胞 白血病抑制因子 白细胞介素6 血管内皮生长因子A 

分 类 号：R711.71[医药卫生—妇产科学]