摘要
目的探讨子痫前期患者外周血CD4^(+)T细胞中共刺激分子肿瘤坏死因子受体超家族4(tumor necrosis factor receptor super family-4,TNFRSF4)mRNA的表达及临床意义。方法本研究为回顾性病例对照研究,选取2021年6月至2024年4月西安高新医院产科收治的148例子痫前期患者,年龄(30.52±3.25)岁,年龄范围为27~34岁。根据子痫前期临床严重程度的分级标准分为轻度子痫组(n=73)和重度子痫组(n=75)。同期选取于西安高新医院产科进行健康检查的65名健康妊娠者纳入健康妊娠组。收集所有纳入者的临床资料,免疫磁珠法分离CD4^(+)T细胞,贴壁黏附法分离抗原呈递细胞,流式细胞仪检测辅助性T细胞1型(Th1)、辅助性T细胞2型(Th2)细胞占比情况,聚合酶链式反应检测TNFRSF4 mRNA,肿瘤坏死因子受体超家族4配体(OX40L)mRNA相对表达量;酶联免疫吸附法检测干扰素γ,转化生长因子-β(TGF-β),白细胞介素-2(IL-2)水平。Pearson相关分析子痫前期患者TNFRSF4 mRNA与免疫细胞因子的相关性,采用logistic回归分析重度子痫前期发生的影响因素。结果健康妊娠组TNFRSF4 mRNA表达量(1.03±0.02)、OX40L mRNA表达量(1.02±0.03)低于轻度子痫组[(1.31±0.07)、(1.23±0.06)]与重度子痫组[(1.59±0.09)、(1.57±0.08)],且轻度子痫组TNFRSF4、OX40L mRNA表达水平均低于重度子痫组,差异有统计学意义(P<0.05)。重度子痫组干扰素γ[(16.85±1.71)pg/ml]、IL-2[(17.01±1.61)pg/ml]、TNF-β[(350.61±33.54)pg/ml]水平高于健康妊娠组[(10.68±1.11)pg/ml、(11.84±1.24)pg/ml、(216.51±22.28)pg/ml]及轻度子痫组[(12.21±1.22)pg/ml、(12.89±1.31)pg/ml、(261.87±27.04)pg/ml],轻度子痫组患者干扰素γ、IL-2、TNF-β水平高于健康妊娠组,差异有统计学意义(P<0.05)。TNFRSF4 mRNA与OX40L mRNA、干扰素γ、IL-2、TNF-β呈正相关(r=0.711、r=0.619、r=0.767、r=0.759,P<0.05)。logistic回归分析结果显示,TNFRSF4 mRNA≥1.39(OR=1.732,95%CI:1.097~2.367)、OX40L mRNA≥1.37(OR=1.848,95%CI:1.105~2.691)、干扰素γ≥13.52 pg/ml(OR=1.670,95%CI:1.104~2.236)、IL-2≥14.37 pg/ml(OR=1.702,95%CI:1.011~2.393)为重度子痫前期发生的危险因素(P<0.05)。结论TNFRSF4 mRNA≥1.39是重度子痫前期发生的危险因素,随子痫前期严重程度增加,患者外周血CD4^(+)T细胞中TNFRSF4表达上调。
Objective To explore the expression and clinical significance of co-stimulatory molecule tumor necrosis factor receptor super family-4(TNFRSF4)mRNA in peripheral blood CD4^(+)T cells of patients with preeclampsia.Methods This study was a retrospective case-control study,a total of 148 patients with preeclampsia admitted to department of Obstetrics in Xi′an Gaoxin Hospital from June 2021 to April 2024 were selected,aged(30.52±3.25)years old,ranging from 27 to 34 years old.According to the clinical severity,they were divided into the mild eclampsia group(n=73)and the severe eclampsia group(n=75).During the same period,65 healthy pregnant women who underwent health examinations at department of Obstetrics in Xi′an Gaoxin Hospital were selected and included in the healthy pregnancy group.The clinical data of the included subjects were collected.CD4^(+)T cells were isolated by immunomagnetic bead method,antigen-presenting cells were isolated by adhesion method,the proportions of T helper cell 1(Th1)and T helper cell 2(Th2)cells were detected by flow cytometry,and TNFRSF4 mRNA was detected by polymerase chain reaction.Relative expression level of TNFRSF4 mRNA、OX40 ligand(OX40L)mRNA were detected by polymerase chain reaction.The levels of interferon-γ,transforming growth factor-β(TGF-β),and interleukin-2(IL-2)were detected by enzyme-linked immunosorbent assay.Pearson correlation analysis was used to analyze the correlation between TNFRSF4 mRNA and immune cytokines in patients with preeclampsia,and logistic regression was used to analyze the influencing factors of severe preeclampsia.Results The expression levels of TNFRSF4 mRNA(1.03±0.02)and OX40L mRNA(1.02±0.03)in the healthy pregnancy group were lower than those in the mild eclampsia group[(1.31±0.07),(1.23±0.06)]and the severe eclampsia group[(1.59±0.09),(1.57±0.08)].Moreover,the expression levels of TNFRSF4 and OX40L mRNA in the mild eclampsia group were lower than those in the severe eclampsia group,and the differences were statistically significant(P<0.05).The levels of interferon-γ[(16.85±1.71)pg/ml],IL-2[(17.01±1.61)pg/ml],and TNF-β[(350.61±33.54)pg/ml]in the severe eclampsia group were higher than those in the healthy pregnancy group[(10.68±1.11)pg/ml,(11.84±1.24)pg/ml,(216.51±22.28)pg/ml]and the mild eclampsia group[(12.21±1.22)pg/ml,(12.89±1.31)pg/ml,(261.87±27.04)pg/ml].The levels of interferon-γ,IL-2 and TNF-βin the mild eclampsia group were higher than those in the healthy pregnancy group,and the differences were statistically significant(P<0.05).TNFRSF4 mRNA was positively correlated with OX40L mRNA,interferon-γ,IL-2,and TNF-β(r=0.711,r=0.619,r=0.767,r=0.759,P<0.05).The results of logistic regression analysis showed that TNFRSF4 mRNA≥1.39(OR=1.732,95%CI:1.097 to 2.367)and OX40L mRNA≥1.37(OR=1.848,95%CI:1.105 to 2.691),interferon-γ≥13.52 pg/ml(OR=1.670,95%CI:1.104 to 2.236),IL-2≥14.37 pg/ml(OR=1.702,95%CI:1.011 to 2.393)were risk factors for the occurrence of severe preeclampsia(P<0.05).Conclusions TNFRSF4 mRNA≥1.39 is a risk factor for the occurrence of severe preeclampsia.With the increase of the severity of preeclampsia,the expression of TNFRSF4 in CD4^(+)T cells in the peripheral blood of patients is upregulated.
作者
张丽杰
姚姝
周喜英
周杰
唐乐
Zhang Lijie;Yao Shu;Zhou Xiying;Zhou Jie;Tang Le(Department of Obstetrics,Xi′an Gaoxin Hospital,Xi′an 710000,China;Department of Ultrasound,Xi′an Gaoxin Hospital,Xi′an 710000,China;Department of Obstetrics,Xi′an People′s Hospital(Xi′an Fourth Hospital),Xi′an 710004,China)
出处
《中国临床实用医学》
2025年第3期165-170,共6页
China Clinical Practical Medicine
基金
陕西省科技厅一般项目-社会发展领域(2022SF-409)。
