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目的研究转化生长因子(TGF)-β1与TGF-β2在环孢素A(CsA)诱导滋养细胞活力、侵袭与迁移能力中的调节作用。方法收集人早孕期绒毛组织,原代分离滋养细胞,采用酶联免疫吸附试验(ELISA)检测CsA处理后滋养细胞的TGF-β1和TGF-β2分泌水平。四唑盐(MTT)法测定滋养细胞存活和生长。Transwell侵袭与迁移试验检测滋养细胞侵袭与迁移能力。结果 CsA剂量依赖性地抑制人早孕期滋养细胞分泌TGF-β2,但不影响TGF-β1的分泌。外源性加入人重组的TGF-β1与TGF-β2抑制基础的和CsA诱导的滋养细胞侵袭、迁移、活力的增强作用;相反,加入TGF-β1或TGF-β2的中和性抗体,则进一步加强CsA诱导的滋养细胞侵袭、迁移与活力的增强作用。结论 CsA通过下调TGF-β2而不是TGF-β1促进人早孕期滋养细胞的体外侵袭性生长。
Objective To investigate the regulatory effect of transforming growth factor-β1 and TGF-β2 on the ability of cyclosporin A (CsA) -induced trophoblast cell viability, invasion and migration. Methods Human chorionic villi were collected from the first trimester of pregnancy. Trophoblasts were isolated from primary culture. The secretion of TGF-β1 and TGF-β2 in trophoblast cells was detected by enzyme linked immunosorbent assay (ELISA). Tetrazolium salt (MTT) assay for trophoblast survival and growth. Transwell Invasion and Migration Assay to Detect Trophoblast Invasion and Migration. Results CsA dose-dependently inhibited the secretion of TGF-β2 by trophoblasts in early pregnancy, but did not affect the secretion of TGF-β1. Exogenous addition of human recombinant TGF-β1 and TGF-β2 inhibition and CsA-induced trophoblast invasion, migration, increased vitality; the contrary, the addition of TGF-β1 or TGF-β2 neutralizing antibodies, then further Enhance CsA-induced trophoblast invasion, migration and enhance the role of vitality. Conclusion CsA can promote the invasive growth of trophoblasts in human early pregnancy by down-regulating TGF-β2 but not TGF-β1.