阿司匹林对缺氧诱导人HTR-8/SVneo滋养细胞凋亡及sFlt-1、HIF-1α表达的影响  

Effects of aspirin on the apoptosis induced by hypoxia of human HTR-8/SVneo trophoblast cells, the expression of soluble fms-like tyrosine kinase receptor, and hypoxia-inducible factor-1α in the cells

作　　者：徐洁 沈玉叶 徐晖 XU Jie;SHEN Yuye;XU Hui(Xianning Central Hospital,The First Affilated Hospital of Hubei university of Scienc and Technology,437000)

机构地区：[1]湖北省咸宁市中心医院,湖北科技学院附属第一医院,437000

出　　处：《中国计划生育学杂志》2023年第2期240-245,485,共7页Chinese Journal of Family Planning

基　　金：咸宁市中心医院科研项目(2021XYB020)。

摘　　要：目的:探讨阿司匹林对缺氧诱导人HTR-8/SVneo滋养细胞凋亡及可溶性类fms酪氨酸激酶-1(sFLT-1)、低氧诱导因子1α(HIF-1α)表达的影响。方法:人HTR-8/SVneo滋养细胞分为正常对照组、缺氧模型组(2%O_(2)、5%CO_(2)、93%N_(2))、阿司匹林低(0.05mmol/L)、中(0.1mmol/L)、高剂量组(0.2mmol/L);培养结束后,MTT法测定细胞活力,流式细胞仪测定细胞凋亡水平及细胞周期,血清培养基基质胶培养测定细胞血管形成能力,RT-PCR法及蛋白印记法测定细胞sFlt-1、HIF-1α水平。结果:缺氧模型组OD值、存活率、血管形成能力、HIF-1α mRNA和蛋白表达均低于正常对照组及阿司匹林各剂量组,但随着阿司匹林剂量增上述各指标逐渐降低;缺氧模型组凋亡率、G1期、sFlt-1 mRNA和蛋白表达均高于正常对照组和阿司匹林各剂量组,但随着阿司匹林剂量增加凋亡率、G1期、sFlt-1 mRNA和蛋白表达逐渐升高(均P<0.05)。结论:低剂量阿司匹林可促进缺氧环境下HTR-8/SVneo细胞增殖、血管形成,抑制细胞凋亡。其机制可能与低剂量阿司匹林能抑制缺氧环境下HTR-8/SVneo细胞sFlt-1表达,促进HIF-1α表达有关。Objective: To explore the effects of aspirin on the apoptosis induced by hypoxia of human HTR-8/SVneo trophoblast cells, the expressions of soluble fms-like tyrosine kinase receptor-1(sFlt), and hypoxia-inducible factor-1α(HIF-1α) in the cells. Methods: The human HTR-8/SVneo trophoblasts cells were divided into normal control group and hypoxia model group(the cells were given 2% O_(2), 5% CO_(2), and 93% N_(2)). The cells in the two groups were treated by low-dose aspirin(0.05 mmol/L), medium-dose aspirin(0.1 mmol/L), or high-dose aspirin(0.2 mmol/L). After culture, MTT method was used to measure the cell viability, flow cytometry was used to measure cell apoptosis level and cell cycle, serum medium Matrigel culture was used to measure the cell angiogenesis ability, and the levels of sFlt-1 and HIF-1α in cells were detected by RT-PCR and Western blotting method. Results: The OD value, the survival rate, the angiogenesis ability, and the HIF-1α mRNA and protein expressions of the cells in the hypoxia model group were significantly lower than those of the cells in the normal control group, and which of the cells after treated by low aspirin, medium-dose, and high-dose of aspirin had decrease gradudally. The apoptosis rate, the G1 phase rate, and the sFlt-1 mRNA and protein expressions of the cells in the hypoxia model group were significantly higher than those of the cells in the normal control group, and which of the cells after treated by low aspirin, medium-dose, and high-dose of aspirin had increase gradudally(all P<0.05). Conclusion: The low dose of aspirin can promote the proliferation,angiogenesis,and inhibit apoptosis of HTR-8/SVneo cells under hypoxia.The mechanism is related to the low dose of aspirin inhibiting the expression of sFlt-1and promoting the expression of HIF-1αof the HTR-8/SVneo cells under hypoxia.

关 键 词：先兆子痫 不同剂量阿司匹林 缺氧 人HTR-8/SVneo滋养细胞 可溶性类fms酪氨酸激酶-1 低氧诱导因子1Α 

分 类 号：R965[医药卫生—药理学]