重度子痫前期患者孕期子宫动脉血流动力学指标与产后胎盘组织中PARP-1和TNF-α表达的相关性研究

Correlation between uterine artery hemodynamic parameters during pregnancy and the expression of PARP-1 and TNF-α in postpartum placental tissue in patients with severe preeclampsia

摘要

目的 探讨重度子痫前期(PE)患者孕期子宫动脉血流动力学指标与产后胎盘组织中多聚ADP核糖转移酶(PARP-1)和肿瘤坏死因子-α(TNF-α)表达的相关性。方法 选取2021年1月至2023年1月唐山市妇幼保健院收治的72例PE患者为研究对象(PE组),根据病情严重程度将其分为轻度PE组(37例)与重度PE组(35例),选取同期在院分娩的41例正常孕妇为对照组,比较重度PE组、轻度PE组、对照组孕期子宫动脉血流动力学指标[血流速度峰谷比(S/D)、阻力指数(RI)、搏动指数(PI)];比较重度PE组与轻度PE组患者的临床资料;采用多因素Logistic回归分析发生重度PE的影响因素;采用实时荧光定量PCR(qRT-PCR)法检测各组患者产后胎盘组织中PARP-1 mRNA和TNF-α mRNA的表达水平;采用Pearson法分析重度PE患者孕期子宫动脉血流动力学指标与产后胎盘组织中PARP-1和TNF-α表达的相关性。结果 重度PE组、轻度PE组、对照组的孕期子宫动脉血流动力学指标PI、RI及S/D比较,差异均有统计学意义(F值分别为69.993、25.111、16.369,P<0.05);重度PE组与对照组(t值分别为16.624、9.988、8.080)、轻度PE组与对照组(t值分别为6.085、3.942、4.157)、重度PE组与轻度PE组(t值分别为10.373、5.958、3.889)的孕期子宫动脉血流动力学指标PI、RI及S/D比较,差异均有统计学意义(P<0.05)。重度PE组患者的收缩压、舒张压及尿蛋白均明显高于轻度PE组,经比较差异均有统计学意义(t值分别为4.881、5.605、3.075,P<0.05)。多因素Logistic回归分析显示,尿蛋白(OR=2.231,95%CI:1.410~3.529)、PI(OR=1.973,95%CI:1.344~2.897)、RI(OR=2.157,95%CI:1.440~3.230)、S/D(OR=1.952,95%CI:1.283~2.969)均为影响重度PE发生的独立危险因素(P<0.05)。重度PE组、轻度PE组、对照组的产后胎盘组织中PARP-1 mRNA、TNF-α mRNA表达水平比较,差异均有统计学意义(F值分别为47.129、48.561,P<0.05);重度PE组与对照组(t值分别为13.653、13.523)、轻度PE组与对照组(t值分别为5.094、9.302)、重度PE组与轻度PE组(t值分别为8.426、4.253)的产后胎盘组织中PARP-1 mRNA、TNF-α mRNA表达水平比较,差异均有统计学意义(P<0.05)。Pearson法进行相关性分析,结果显示,重度PE组患者孕期子宫动脉血流动力学指标PI、RI及S/D与产后胎盘组织中PARP-1、TNF-α表达均呈正相关(r=0.513~0.662,P<0.05)。结论 重度PE患者孕期子宫动脉血流动力学指标及产后胎盘组织中PARP-1 mRNA和TNF-α mRNA表达水平均较高,且孕期子宫动脉血流动力学指标与胎盘组织中PARP-1、TNF-α的表达均呈正相关,两者均与病情的发生及发展密切相关。

Abstract

Objective To explore the correlation between the hemodynamic indicators of uterine artery blood flow during pregnancy in patients with severe preeclampsia (PE) and the expression of poly (ADP-ribose) polymerase-1 (PARP-1) and tumor necrosis factor-α (TNF-α) in postpartum placental tissue. Methods 72 PE patients admitted to Tangshan Maternal and Child Health Hospital from January 2021 to January 2023 were selected as the PE group. Based on the severity of the condition, the patients were divided into a mild PE group (37 cases) and a severe PE group (35 cases), with 41 normal pregnant women who delivered in the same period serving as the control group. To compare the hemodynamic parameters of uterine artery blood flow during pregnancy among the severe PE group, mild PE group, and control group, including the peak-to-end diastolic flow velocity ratio (S/D), resistance index (RI), and pulsatility index (PI). To compare the clinical data of patients in the severe PE group and the mild PE group. Multivariate logistic regression was used to analyze the factors affecting the occurrence of severe PE, and qRT-PCR method was used to detect the expression of PARP-1 mRNA and TNF-α mRNA in postpartum placental tissue of three groups. Pearson method was used to analyze the correlation between uterine artery hemodynamic parameters during pregnancy and the expression of PARP-1 and TNF-α in postpartum placental tissue in severe PE patients. Results The differences in PI, RI and S/D of uterine artery hemodynamic parameters during pregnancy were statistically significant in the comparison of patients in the severe PE group, mild PE group and control group (F-values were 69.993, 25.111, and 16.369, respectively, P<0.05); the differences in uterine artery hemodynamic parameters (PI, RI, and S/D) between the severe PE group and the control group (t-values were 16.624, 9.988 and 8.080, respectively), the mild PE group and the control group (t-values were 6.085, 3.942 and 4.157, respectively), and the severe PE group and the mild PE group (t-values were 10.373, 5.958 and 3.889, respectively) were statistically significant (P<0.05). The systolic blood pressure, diastolic blood pressure and urinary protein of patients in the severe PE group were significantly higher than those in the mild PE group, and the differences were all statistically significant (t-values were 4.881, 5.605 and 3.075, respectively, P<0.05). Multivariate logistic regression analysis showed that urinary protein (OR=2.231, 95%CI: 1.410-3.529), PI (OR=1.973, 95%CI: 1.344-2.897), RI (OR=2.157, 95%CI: 1.440-3.230), S/D (OR=1.952, 95%CI: 1.283-2.969) were all independent risk factors influencing the occurrence of severe PE (P<0.05). The differences in PARP-1 mRNA and TNF-α mRNA expression levels were statistically significant in the comparison of patients in the severe PE group, mild PE group and control group (F-values were 47.129, and 48.561, respectively, P<0.05). The differences in PARP-1 mRNA and TNF-α mRNA expression levels in postpartum placental tissue between the severe PE group and the control group (t-values were 13.653 and 13.523, respectively), the mild PE group and the control group (t-values were 5.094 and 9.302, respectively), and the severe PE group and the mild PE group (t-values were 8.426 and 4.253, respectively) were statistically significant (P<0.05). Pearson correlation showed a positive correlation between the uterine artery hemodynamic parameters including PI, RI, and S/D during pregnancy in severe PE patients and the expression of PARP-1 and TNF-α in postpartum placental tissue (r=0.513-0.662, P<0.05). Conclusion Patients with severe PE have higher uterine artery hemodynamic parameters during pregnancy and the expression of PARP-1 and TNF-α in postpartum placental tissue, and there was a positive correlation between uterine artery hemodynamic parameters during pregnancy and the expression of PARP-1 and TNF-α in postpartum placental tissue, both factors are closely related to the occurrence and development of disease.

关键词

子痫前期 / 多聚ADP核糖转移酶 / 肿瘤坏死因子-α / 子宫动脉血流动力学

Key words

preeclampsia / poly(ADP-ribose)polymerase / tumor necrosis factor-α / uterine artery hemodynamics

参考文献

[1] Helmo F R, Lopes A M M, Carneiro A C D M, et al. Angiogenic and antiangiogenic factors in preeclampsia[J]. Pathol Res Pract, 2018, 214(1): 7-14.

[2] Nirupama R, Divyashree S, Janhavi P, et al. Preeclampsia: pathophysiology and management[J]. J Gynecol Obstet Hum Reprod, 2021, 50(2): 101975.

[3] Lee S, Shin J, Kim J S, et al. Targeting TBK1 attenuates LPS-induced NLRP3 inflammasome activation by regulating of mTORC1 pathways in trophoblasts[J]. Front Immunol, 2021, 12: 743700.

[4] 颜露春, 朱广源, 李小林, 等. 子痫前期孕妇外周血sFlt-1、PIGF、PP-13、sEng的表达及其与子宫动脉血流的相关性研究[J]. 中国生育健康杂志, 2019, 30(3): 237-240.

[5] Edwards A D, Marecki J C, Byrd A K, et al. G-Quadruplex loops regulate PARP-1 enzymatic activation[J]. Nucleic Acids Res, 2021, 49(1): 416-431.

[6] Pazzaglia S, Pioli C. Multifaceted role of PARP-1 in DNA repair and inflammation: pathological and therapeutic implications in cancer and non-cancer diseases[J]. Cells, 2019, 9(1): 41.

[7] Song Y, Jo S, Chung J Y, et al. RNA interference-mediated suppression of TNF-α converting enzyme as an alternative anti-TNF-α therapy for rheumatoid arthritis[J]. J Control Release, 2021, 330: 1300-1312.

[8] Koper-Lenkiewicz O M, Sutkowska K, Wawrusiewicz-Kurylonek N, et al. Proinflammatory cytokines (IL-1, -6, -8, -15, -17, -18, -23, TNF-α) single nucleotide polymorphisms in rheumatoid arthritis-a literature review[J]. Int J Mol Sci, 2022, 23(4): 2106.

[9] 中华医学会妇产科学分会妊娠期高血压疾病学组. 妊娠期高血压疾病诊治指南(2020)[J]. 中华妇产科杂志, 2020, 55(4): 227-238.

[10] 杨怡珂, 漆洪波. 美国妇产科医师学会(ACOG)“妊娠期高血压和子痫前期指南2019版”要点解读(第一部分)[J]. 中国实用妇科与产科杂志, 2019, 35(8): 895-899.

[11] 王小凤, 韩程成, 康瑛, 等. CircPAPPA、miR-3127-5p表达与子痫前期妊娠结局的相关性分析[J]. 中国妇幼健康研究, 2023, 34(3): 35-40.

[12] Chen H, Meng T, Liu X, et al. Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells[J]. Int J Clin Exp Pathol, 2015, 8(10): 12718-12727.

[13] Jin J, Gao L, Zou X, et al. Gut dysbiosis promotes preeclampsia by regulating macrophages and trophoblasts[J]. Circ Res, 2022, 131(6): 492-506.

[14] Yu N, Cui H, Chen X, et al. First trimester maternal serum analytes and second trimester uterine artery Doppler in the prediction of preeclampsia and fetal growth restriction[J]. Taiwan J Obstet Gynecol, 2017, 56(3): 358-361.

[15] Wang Y, Luo W, Wang Y. PARP-1 and its associated nucleases in DNA damage response[J]. DNA Repair (Amst), 2019, 81: 102651.

[16] Gao Y, Bai L, Zhou W, et al. PARP-1-regulated TNF-α expression in the dorsal root ganglia and spinal dorsal horn contributes to the pathogenesis of neuropathic pain in rats[J]. Brain Behav Immun, 2020, 88: 482-496.

[17] Li K, Qiu H, Yan J, et al. The involvement of TNF-α and TNF-β as proinflammatory cytokines in lymphocyte-mediated adaptive immunity of Nile tilapia by initiating apoptosis[J]. Dev Comp Immunol, 2021, 115: 103884.

[18] Woznicki J A, Saini N, Flood P, et al. TNF-α synergises with IFN-γ to induce caspase-8-JAK1/2-STAT1-dependent death of intestinal epithelial cells[J]. Cell Death Dis, 2021, 12(10): 864.

[19] 朱宇, 王素萍, 史彦涛, 等. TNF-α、COX-2及CXCL12在子痫前期患者胎盘组织中的表达及意义[J]. 中国妇幼保健, 2019, 34(11): 2608-2611.

[20] Zhang D, Hu X, Li J, et al. DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD+ depletion in experimental atrial fibrillation[J]. Nat Commun, 2019, 10(1): 1307.

[21] 庄万祝, 戚怀钻, 张果, 等. 早发重度子痫前期患者子宫动脉血流动态监测对胎儿生长受限的预测效能[J]. 中国妇产科临床杂志, 2023, 24(5): 526-527.

基金资助

河北省医学科学研究课题计划项目(20221770)