TNF-α及sTNFRⅠ对子宫内膜异位症在位内膜基质细胞的作用

The effects of TNF-α and sTNFRⅠ on stormal cells of endometriosis

目的:探讨肿瘤坏死因子α(tumor necrosis factor,TNF-α)和可溶性肿瘤坏死因子受体(soluble TNFRI,sTNFRI)对体外培养的子宫内膜异位症(Endometriosis)患者在位内膜基质细胞的影响,为子宫内膜异位症的生物学治疗提供新思路。方法:对EMS患者的在位子宫内膜基质细胞进行体外培养,分别用不同浓度的TNF-α(0、0.1、1.0、10.0和100.0ng/ml)或者同一浓度TNF-α(1ng/ml)培养不同时间(4、8、12、24、48和72h)或者TNF-α(1ng/ml)和sTNFRⅠ(2#g/ml)对基质细胞进行刺激并收集细胞上清液,利用双抗体夹心ELISA检测细胞培养上清液中IL-6、基质金属蛋白酶-3(matrix metalloproteinases,MMP-3)的水平。结果:TNF-α可促进体外培养的EMS子宫内膜基质细胞IL-6、MMP-3的分泌,而且IL-6、MMP-3浓度与TNF-α之间存在剂量、时间依赖关系(P<0.05),而sTNFRⅠ具有抑制TNF-α的作用。结论:TNF-α在EMS的发病机制中发挥重要的作用,其对EMS患者子宫内膜基质细胞的促黏附、侵袭、增殖等作用可能是通过促进IL-6、MMP-3的分泌来完成的;sTNFRⅠ有望用于EMS生物学治疗。

Objective：To explore the effects of TNF-α and sTNFR I on cuhured eutopic endometrial stroma cells from endometriosis patients and find new biological therapy to endometriosis, nethods：Stroma cells from eutopic endometrium were cultured in vitro. TNF-α （0,0.1,1,10,and 1（30 ng/ml） was added to the medium in dose-responds experiment. TNF-alpha （1 ng/ml） was added for 0,4,8,12,24,48 and 72 hours in time-course experiment. TNF-α （0.1,1 and 10 ng/ml） and sTNFR I （2 μg/ml） were added for 12 hours. Then the supematant were collected to evaluate the productions of IL-6 and MMP-3. Results：The productions of IL-6 and MMP-3 in the supematant of stroma cells from endometriosis were promoted by TNF-alpha in a dose-dependent and timedependent manner. The productions of IL-6 and MMP-3 in the supematant of stroma cells from endometriosis were promoted by TNF- alpha were decreased by sTNFR Ⅰ . Conclusion：TNF-μ may promote the attachment and invade of stroma cells from women with endometriosis though inducing the expression of IL-6 and MMP-3 and play a central role in the pathogenesis of endometriosis, sTNFR Ⅰ may be the potential target for biological therapy to endometriosis.