论文部分内容阅读
目的:研究低分子肝素(LMWH)对不同氧浓度下早孕绒毛滋养层细胞侵袭力的影响。方法:取妊娠8~10周正常绒毛组织,酶消化法分离人早孕绒毛滋养层细胞,分别置2%和20%O_2分压的细胞培养箱培养。用不同浓度LMWH(0、0.1、5、10IU/ml)处理滋养细胞,观察滋养层细胞侵袭力的改变,检测细胞中HIF-1α、MMP-2、MMP-9、TIMP-2、TIMP-3表达。结果:低氧浓度下,早孕绒毛滋养层细胞的侵袭能力随着LMWH浓度(0,0.1,5IU/ml)升高而增强,但高浓度的LMWH(10IU/ml)对其有抑制作用;随着LMWH浓度增加,HIF-1α和MMP-2表达呈先上升后下降的趋势;TIMP-2、TIMP-3表达改变的趋势与MMP-2相同。正常氧浓度下的滋养层细胞,其侵袭能力未见显著增强,各细胞因子的表达无上调。结论:低氧环境下,一定浓度的LMWH可提高早孕绒毛滋养层细胞的侵袭能力,其发生机制可能是通过诱导、增强滋养层细胞HIF-1α和MMP-2基因表达。
AIM: To investigate the effect of low molecular weight heparin (LMWH) on invasiveness of trophoblast cells in early pregnancy of villus under different oxygen concentrations. Methods: Normal chorionic villi were collected from 8 to 10 weeks of gestation, and the trophoblast cells of human chorionic villi were isolated by enzymatic digestion. The cells were cultured in 2% and 20% O2 partial pressure cell culture incubator. Trophoblast cells were treated with different concentrations of LMWH (0, 0.1, 5 and 10 IU / ml) to observe the change of invasiveness of trophoblast cells. The expressions of HIF-1α, MMP-2, MMP-9, TIMP-2 and TIMP- expression. Results: The invasive ability of trophoblast cells in early pregnancy was enhanced with the increase of LMWH concentration (0,0.1,5 IU / ml), but was inhibited by high concentration of LMWH (10 IU / ml) With the increase of LMWH concentration, the expression of HIF-1α and MMP-2 first increased and then decreased; the trend of TIMP-2 and TIMP-3 expression changed the same as that of MMP-2. Trophoblast cells under normal oxygen concentration showed no significant enhancement of invasion ability, and no up-regulation of the expression of various cytokines. CONCLUSION: Under hypoxia, a certain concentration of LMWH can enhance the invasion ability of trophoblast cells in early pregnancy, and its mechanism may be through the induction and enhancement of gene expression of HIF-1α and MMP-2 in trophoblastic cells.