目的 探讨肿瘤坏死因子受体1在绒毛组织中的表达及其与不明原因早期自然流产的关系.方法 采用共聚焦激光显微镜和免疫组化技术,对31例妊娠6～10周不明原因早期自然流产患者(流产组)和30例同期妊娠的健康妇女(对照组)绒毛组织中肿瘤坏死因子受体1的表达进行半定量和定位检测.结果 共聚焦显微镜观察结果为:流产组绒毛间质、血管内皮、细胞滋养层、合体滋养层细胞肿瘤坏死因子受体1表达荧光强度分别为35.99±6.35、44.11±11.89、51.40±15.26和50.76±15.74,对照组分别为32.64±5.01、42.82±8.13、49.67±10.19和48.70±10.40.流产组绒毛间质肿瘤坏死因子受体1表达荧光强度高于对照组,有显著性差异(t=2.208,P<0.05),血管内皮、细胞滋养层、合体滋养层细胞的两组差异均无显著性(t分别为0.474、0.585、0.503,均P>0.05).免疫组化结果为:流产组绒毛间质、血管内皮、细胞滋养层及合体滋养层细胞肿瘤坏死因子受体1表达率分别为100.00%(31/31)、80.65%(25/31)、100.00%(31/31)和90.32%(28/31),对照组分别为75.00%(18/24)、58.33%(14/24)、100.00%(24/24)和95.83%(23/24),流产组绒毛间质肿瘤坏死因子受体1阳性表达率明显高于对照组,经Fisher's精确概率法检验,差异具有显著性(P=0.001).免疫组化还显示:流产组中,与合体滋养层接触的细胞滋养层和血管内皮细胞肿瘤坏死因子受体1阳性表达增强.结论 绒毛间质细胞肿瘤坏死因子受体1表达水平的升高,可能通过调节肿瘤坏死因子-α的效应,导致胎儿界面局部绒毛组织间质细胞的功能改变或损害;部分细胞滋养层及血管内皮细胞肿瘤坏死因子受体1表达水平的升高加速了细胞滋养层细胞的程序性死亡,使细胞滋养层生长受限制,可能与不明原因早期自然流产的发生有关.%Objective To investigate expression of tumor necrosis factor receptor 1 (TNFR1) in chorionic villi of pregnant women with unexplained early spontaneous abortion(UESA) and relationship of the expression with UESA. Methods 31 pregnant women with UESA at 6~10 weeks of gestation were included in abortion group and 30 normal pregnant women were included in the control group. Chorionic villous specimen in the two groups were taken at the time of abortion. Confocal laser scanning microscope (CLSM) and immunohistochemistry were used to conduct a semi-quantitative detection and location detection of expression of TNFR1 in chorionic villous tissues of all women. Results The fluorescence intensity of expression of TNFR1 in villous stromal cells, vascular endothelial cells, cytotrophoblast and syncytiotrophoblast cells of women in the abortion group determined by CLSM were 35.99±6.35, 44.11±11.89, 51.40±15.26 and 50.76±15.74 respectively, and those of women in the control group were 32.64±5.01, 42.82±8.13, 49.67±10.19 and 48.70±10.40 respectively. The fluorescence intensity of expression of TNFR1 in villous stromal cells in the abortion group was greater than that in the control group(t=2.208, P<0.05). While, in expression intensity of TNFR1 in villous vascular endothelial cells, cytotrophoblast and syncytiotrophoblast cells, there were no significant differences between the two groups (t=0.474, 0.585, 0.503 respectively, all P>0.05). The expression rates of TNFR1 in villous stromal cells, vascular endothelial cells, cytotrophoblast and syncytiotrophoblast cells of women in the abortion group determined by immunohistochemistry were 100.00% (31/31), 80.65% (25/31), 100.00% (31/31) and 90.32% (28/31) respectively, and those in the control group were 75.00% (18/24), 58.33% (14/24), 100.00% (24/24) and 95.83% (23/24) respectively. Of which, the expression rate of TNFR1 in villous stromal cells of women in the abortion group was higher than that in the control group and the difference was significant by Fisher's accuracy probability test (100.00% vs 75%, P=0.001). Immunohistochemistry results also revealed that expression rates of TNFR1 in both villous cytotrophoblast and vascular endothelial cells that contact with syncytiotrophoblast were stronger than that in the control group. Conclusion The increased expression of TNFR1 in villous stromal cells, possibly through regulating effects of TNF-α, causes pathological changes or tissue damage in local chorionic villi, and increased TNFR1 expression in parts of cytotrophoblast cells and vascular endothelial cells accelerates programmed cell death of cytotrophoblasts and then limits their growth, which maybe lead to development of UESA.
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