低分子量肝素对滋养层细胞MMP-2、TIMP-2表达及侵袭力的影响  

Effects of low-molecular weight heparin on MMP-2,TIMP-2 expression and invasiveness of cytotrophoblastic cells

作　　者：马小静[1] 徐永萍[1] 邓新超[1] 徐晖[1] 马丽娜[1] 

机构地区：[1]山东大学第二医院妇产科,山东济南250033

出　　处：《中国病理生理杂志》2010年第3期554-557,共4页Chinese Journal of Pathophysiology

摘　　要：目的:探讨低分子量肝素对体外培养人早孕绒毛滋养层细胞MMP-2、TIMP-2表达及侵袭力的影响。方法:将经胰蛋白酶/DNA酶Ⅰ联合消化,通过Percoll细胞分离液纯化得到的绒毛滋养层细胞进行体外培养。采用不同浓度低分子量肝素干预培养24h后,ELISA法测定细胞上清液中MMP-2、TIMP-2的浓度;采用Tr-answell小室观察滋养层细胞的侵袭能力。结果:不同浓度的低分子量肝素(1.0×102IU/L,1.0×103IU/L,1.0×104IU/L)干预人早孕绒毛滋养层细胞后,与对照组相比,MMP-2的表达上调,滋养层细胞侵袭力增强,在1.0×103IU/L时MMP-2表达最高,滋养层细胞侵袭力最强(P<0.05)。TIMP-2的表达随着低分子量肝素浓度的增加而逐渐下降,与对照组比较,在1.0×103IU/L、1.0×104IU/L组明显降低(P<0.05),但1.0×103IU/L组与1.0×104IU/L组之间TIMP-2的表达无差异(P>0.05)。结论:低分子量肝素可能直接通过影响绒毛滋养层细胞MMP-2、TIMP-2的表达进而影响绒毛滋养层细胞的侵袭能力。AIM： To investigate the hypothesis that low-molecular weight heparin （LMWH） regulates in vitro cytotrophoblast invasiveness and production of metalloproteinases-2 （MMP-2）, tissue inhibitor of metalloproteinas-2 （TIMP-2）. METHODS： Chorionic villi tissue of normal 6-8 weeks pregnancy was obtained. Trophoblastic cells were collected by trypsin-collagenase digestion and Percoll gradient centrifugation. The cytotrophoblastic cells were cultured for 24 h and divided into 4 groups according to the concentrations （1.0×102 IU/L, 1.0×103 IU/L or 1.0×104 IU/L） of LMWH adding into the medium. The contents of MMP-2 and TIMP-2 in cell culture supernatants were measured by the method of ELISA. Cytotrophoblast invasiveness was determined by Transwell chamber assay. RESULTS： With the increasing concentrations of LMWH, the invasion activity of cytotrophoblastic cells and MMP-2 secretion were increased. At concentration of 1.0×103IU/L, LMWH greatly enhanced cytotrophoblast invasiveness and the expression of MMP-2 （P〈0.05）. The levels of TIMP-2 were decreased after intervention with LMWH. At concentration of 1.0×103IU/L or 1.0×104 IU/L, LMWH induced a significant decrease in TIMP-2 expression. No significant difference between group 1×103IU/L and group 1.0×104 IU/L was observed （P〉0.05）. CONCLUSION： LMWH might regulate cytotrophoblast invasiveness in vitro by influencing the expression of MMP-2 and TIMP-2 in cytotrophoblastic cells.

关 键 词：流产 肝素 低分子量 滋养细胞 基质金属蛋白酶 

分 类 号：R711[医药卫生—妇产科学]