SHH信号通路对子痫前期患者滋养细胞凋亡和侵袭的影响及其机制

doi:10.13481/j.1671-587x.20180310

摘要/Abstract

摘要： 目的：探讨激活SHH信号通路对子痫前期（PE）患者滋养细胞凋亡和侵袭的影响，并阐明其作用机制。方法：将HTR8/SVneo细胞分为正常对照组、缺氧/复氧（H/R）处理组和purmorphamine+H/R处理组。Western blotting法检测PE胎盘组织和正常妊娠晚期胎盘组织及各组HTR8/SVneo细胞中SHH信号通路相关蛋白SHH、Ptch1、Smo、Gli1和Gli3蛋白表达水平，流式细胞术（FCM）检测各组HTR8/SVneo细胞的凋亡率，Transwell小室法检测各组HTR8/SVneo细胞的穿膜细胞数，Western blotting法检测各组HTR8/SVneo细胞中基质金属蛋白酶2（MMP-2）和基质金属蛋白酶9（MMP-9）蛋白表达水平。结果：PE胎盘组织HTR8/SVneo细胞中SHH、Ptch1、Smo、Gli1和Gli3蛋白表达水平均明显低于正常妊娠晚期胎盘组织（P<0.05）；H/R处理组HTR8/SVneo细胞中SHH、Ptch1、Smo、Gli1、Gli3、MMP-2和MMP-9蛋白表达水平及穿膜细胞数均明显低于正常对照组，细胞凋亡率明显高于正常对照组（P<0.05）；purmorphamine+H/R处理组HTR8/SVneo细胞中SHH、Ptch1、Smo、Gli1、Gli3、MMP-2和MMP-9蛋白表达水平及穿膜细胞数均明显高于H/R处理组（P<0.05），细胞凋亡率明显低于H/R处理组（P<0.05）。结论：激活SHH信号通路可减少PE患者胎盘组织中HTR8/SVneo细胞凋亡，并通过上调MMP-2和MMP-9表达提高细胞的侵袭能力。

关键词: 子痫前期, 滋养细胞, 细胞凋亡, 胎盘组织, SHH信号通路

Abstract: Objective: To investigate the effect of activation of SHH signaling pathway on the apoptosis and invasion of the trophoblast cells in the preeclampsia(PE) patients,and to clarify its mechanism. Methods: The HTR8/SVneo cells were divided into normal control group,hypoxia/reoxygenation(H/R) treatment group and purmorphamine+H/R treatment group. The expression levels of SHH signaling pathway related proteins SHH,Ptch1,Smo,Gli1,and Gli3 in the placenta tissues of PE and late trimester of normal pregnancy were detected by Western blotting method;the apoptotic rates of HTR8/SVneo cells in various groups were detected by flow cytometry(FCM); Transwell assay was used to detect the number of transmembrane cells; the expression levels of matrix metalloproteinase-2(MMP-2) and metalloproteinase-9(MMP-9) proteins in the HTR8/SVneo cells in various groups were detected by Western blotting method. Results: The expression levels of SHH,Ptch1,Smo,Gli1 and Gli3 proteins in the placenta tissue of PE were significantly lower than those in normal pregnancy placenta tissue (P<0.05);the expression levels of SHH,Ptch1,Smo,Gli1,Gli3,MMP-2,and MMP-9 proteins and the number of transmembrane cells in H/R treatment group were significantly lower than those in normal control group(P<0.05),and the apoptotic rate was significantly higher than that in normal control group (P<0.05); the expression levels of SHH,Ptch1,Smo,Gli1,Gli3,MMP-2,and MMP-9 proteins and the number of transmembrane cells in purmorphamine+H/R treatment group were significantly higher than those in H/R treatment group(P<0.05),and the apoptotic rate was significantly lower than that in H/R treatment group (P<0.05). Conclusion: The activation of SHH signaling pathway can reduce the apoptosis of HTR8/SVneo cells in the placental tissue of the PE patients and promote the cell invasion by up-regulating the expressions of MMP-2 and MMP-9.

Key words: preeclampsia, apoptosis, trophoblast cells, SHH signaling pathway, placental tissue

中图分类号:

R742.1

任艳芳, 姜永杰, 张秀玲, 姜姗, 王玉红. SHH信号通路对子痫前期患者滋养细胞凋亡和侵袭的影响及其机制[J]. 吉林大学学报(医学版), 2018, 44(03): 510-515.

REN Yanfang, JIANG Yongjie, ZHANG Xiuling, JIANG Shan, WANG Yuhong. Effect of SHH signaling pathway on apoptosis and invasion of trophoblast cells in preeclampsia patientsand its mechanism[J]. Journal of Jilin University Medicine Edition, 2018, 44(03): 510-515.

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