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目的:探讨粘着斑激酶(focal adhesion kinase,FAK)信号通路在环孢素A(cyclosporin A,CsA)调节人滋养细胞体外生长中的作用。方法:收集因非意愿妊娠6~9周要求行人工流产术的正常妊娠妇女的绒毛组织,体外分离培养获得滋养细胞,经CsA和/或FAK抑制剂Y15处理后,免疫荧光检测滋养细胞FAK的磷酸化水平;BrdU检测滋养细胞的增殖;Annexin V/PI检测滋养细胞的凋亡。结果:CsA可明显提高滋养细胞FAK的活化水平,FAK抑制剂Y15可阻断CsA诱导的FAK活化,阻抑CsA对细胞增殖的促进作用(P<0.05)以及对滋养细胞凋亡的抑制作用(P<0.05)。结论:CsA可通过活化FAK信号通路促进人早孕期滋养细胞的体外生长,从而有利于正常妊娠的维持。
Objective: To investigate the role of focal adhesion kinase (FAK) signaling pathway in the regulation of human trophoblast cell growth in vitro by cyclosporin A (CsA). Methods: The villi tissues of normal pregnant women who had abortion induced by unplanned pregnancy from 6 to 9 weeks were collected. Trophoblast cells were isolated and cultured in vitro. After treatment with CsA and / or FAK inhibitor Y15, immunofluorescence was used to detect the expression of FAK Phosphorylation; BrdU detection of trophoblast proliferation; Annexin V / PI detection of trophoblast apoptosis. Results: CsA significantly increased the activation of FAK in trophoblasts, FAK inhibitor Y15 blocked CsA-induced activation of FAK, inhibited the promotion of CsA on cell proliferation (P <0.05), and inhibited the apoptosis of trophoblasts ( P <0.05). Conclusion: CsA can promote the growth of human trophoblast in early pregnancy through activation of FAK signaling pathway, which is beneficial to the maintenance of normal pregnancy.