复发性流产中人巨细胞病毒感染对滋养细胞增殖、侵袭的调控及机制研究

Regulation and Mechanism of Human Cytomegalovirus Infection on Trophoblast Proliferation and Invasion in Recurrent Spontaneous Abortion

为了研究复发性流产(Recurrent spontaneous abortion,RSA)中人巨细胞病毒(Human cytomegalovirus,HCMV)感染对滋养细胞增殖、侵袭的调控及机制,收集RSA患者的绒毛组织,分为HCMV阳性和阴性的绒毛组织,检测过氧化物酶体增殖物激活受体γ(Peroxisome proliferators-activated receptorsγ,PPARγ)的表达水平;培养绒毛滋养细胞株HTR8/SVneo,感染HCMV,用5μmol/L PPARγ拮抗剂GW9662处理,检测细胞增殖活力A490、侵袭数目及细胞周期蛋白D(Cyclin D1)、B淋巴细胞瘤-2基因(B-cell lymphoma-2,bcl-2)、基质金属蛋白酶2(Matrix metalloproteinase 2,MMP2)、锌指转录因子(Slug)的表达水平。结果显示:HCMV阳性的RSA绒毛组织中PPARγ的表达水平高于HCMV阴性的RSA绒毛组织(P<0.05),PPARα、PPARβ的表达水平与HCMV阴性的RSA绒毛组织比较无显著性差异(P>0.05);HCMV组人绒毛膜滋养层细胞(HTR8/SVneo)中PPARγ的表达水平高于对照组(P<0.05),PPARα、PPARβ的表达水平与对照组比较无显著性差异(P>0.05),A490、侵袭数目及CyclinD1、bcl-2、MMP2、Slug的表达水平低于对照组(P<0.05);HCMV+GW9662组HTR8/SVneo细胞中PPARγ的表达水平低于HCMV组,A490、侵袭数目及CyclinD1、bcl-2、MMP2、Slug表达水平高于HCMV组(P<0.05)。从而得出结论:RSA绒毛组织中HCMV感染可能通过增加PPARγ表达抑制滋养细胞的增殖和侵袭。

To investigate the regulation and mechanism of human cytomegalovirus(HCMV)infection on trophoblast proliferation and invasion in recurrent spontaneous abortion(RSA).The chorionic tissues of RSA patients were collected and divided into HCMV positive and negative chorionic tissues.The expression of peroxisome proliferator activated receptorsγ(PPARγ)were detected.Human chorionic trophoblast cell line HTR8/SVneo was cultured,and infected with HCMV.One group was treated with 5μmol/L PPARγantagonist GW9662.Then the cell proliferation activity read at A_(490),invasion number and the expression levels of Cyclin D1,bcl-2,MMP2 and Slug were detected.Results showed that the expression level of PPARγin HCMV positive chorionic tissues were higher than that in HCMV negative chorionic tissues(P<0.05).The expression levels of PPARαand PPARβshowed no significant difference with HCMV negative chorionic tissues(P>0.05).The expression level of PPARγin HTR8/SVneo cells of HCMV group was higher than that in control group(P<0.05).The expression levels of PPARαand PPARβshowed no significant difference with control group(P>0.05),and the A_(490),the number of invasions and the expression levels of CyclinD1,bcl-2,MMP2,Slug were lower than those in the control group(P<0.05).The expression level of PPARγin HTR8/SVneo cells of HCMV+GW9662 group was lower than that in HCMV group(P<0.05),and the A_(490),the number of invasions and the expression levels of CyclinD1,bcl-2,MMP2,Slug were higher than those in the HCMV group(P<0.05).The conclusion is that HCMV infection in chorionic tissue of RSA may inhibit the proliferation and invasion of trophoblasts by increasing the expression of PPARγ.