[1]张金辉,李维玲,闫 璐.子痫前期患者血清lncRNA HIF1A-AS1，CXCL9水平表达与病情程度及不良妊娠结局的关系分析[J].现代检验医学杂志,2024,39(06):73-78+140.[doi:10.3969/j.issn.1671-7414.2024.06.012]
　ZHANG Jinhui,LI Weiling,YAN Lu.Analysis of Relationship between Serum lncRNA HIF1A-AS1, CXCL9 and Disease Severity, Adverse Pregnancy Outcomes in Patients with Preeclampsia[J].Journal of Modern Laboratory Medicine,2024,39(06):73-78+140.[doi:10.3969/j.issn.1671-7414.2024.06.012]
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子痫前期患者血清lncRNA HIF1A-AS1，CXCL9水平表达与病情程度及不良妊娠结局的关系分析()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年06期
页码:
73-78+140
栏目:
论著
出版日期:
2024-11-15

文章信息/Info

Title:
Analysis of Relationship between Serum lncRNA HIF1A-AS1, CXCL9 and Disease Severity, Adverse Pregnancy Outcomes in Patients with Preeclampsia
文章编号:
1671-7414（2024）06-073-07
作者:
张金辉; 李维玲; 闫 璐
（西安高新医院妇产科，西安 710075）
Author(s):
ZHANG Jinhui;  LI Weiling;  YAN Lu
（Department of Gynaecology and Obstetrics, Xi’an Gaoxin Hospital, Xi’an 710075, China）
关键词:
子痫前期; 长链非编码RNA 缺氧诱导因子-1α- 反义链1; CXC 趋化因子配体9; 不良妊娠结局
分类号:
R714.244；R392.11
DOI:
10.3969/j.issn.1671-7414.2024.06.012
文献标志码:
A
摘要:
目的 探讨子痫前期（Preeclanpsia）患者血清长链非编码RNA 缺氧诱导因子-1α- 反义链1（lncRNA HIF1AAS1）、CXC 趋化因子配体9（CXCL9）表达与病情程度及不良妊娠结局的关系。方法 以2021 年1 月～ 2022 年12月西安高新医院收治的83 例子痫前期患者为子痫前期组，根据确诊时间对子痫前期患者进行分组, 分为早发型子痫前期组（n=39）和晚发型子痫前期组（n=44）；根据病情严重程度将子痫前期患者分为轻度子痫前期组（n=51）和重度子痫前期组（n=32）；根据妊娠结局分为正常妊娠结局组（n=56）和不良妊娠结局组（n=27）。收集同期的60 例健康妊娠孕妇为对照组。采用实时荧光定量PCR(qRT-PCR ) 检测血清lncRNA HIF1A-AS1 相对表达量，酶联免疫吸附法（ELISA）检测血清CXCL9 水平。Spearman 秩相关分析血清lncRNA HIF1A-AS1，CXCL9 与病情程度的相关性，Logistic 回归分析子痫前期患者不良妊娠结局影响因素，绘制受试者工作特征（ROC）曲线评估血清lncRNA HIF1AAS1，CXCL9 对不良妊娠结局预测价值。结果 子痫前期组血清lncRNA HIF1A-AS1 相对表达量（0.73±0.26）低于对照组（1.15±0.34），CXCL9 水平（209.34±45.34 pg/ml）高于对照组（116.80±37.76 pg/ml），差异具有统计学意义（t=8.379，12.903，均P<0.05）。早发型子痫前期组血清lncRNA HIF1A-AS1 相对表达量（0.58±0.21）低于晚发型子痫前期组（0.86±0.27），CXCL9 水平（236.60±31.02 pg/ml）高于对照组（185.18±23.63 pg/ml），差异具有统计学意义（t=5.226，8.551，均P<0.05）。重度子痫前期组血清lncRNA HIF1A-AS1 相对表达量（0.52±0.21）低于轻度子痫前期组（0.97±0.34），血清CXCL9 水平（253.38±41.20 pg/ml）高于轻度子痫前期组（159.65±40.79 pg/ml），差异具有统计学意义（t=6.409，10.152，均P<0.05）。血清lncRNA HIF1A-AS1，CXCL9 与子痫前期病情具有相关性（r=-0.627，0.651，均P<0.05）。CXCL9[OR（95%CI）：1.581（1.098 ～ 2.276）] 是子痫前期不良妊娠结局独立危险因素（P<0.05），lncRNA HIF1A-AS1[OR（95%CI）：0.806（0.673 ～ 0.965）] 是保护因素（P<0.05）；早发型子痫前期[OR（95%CI）：1.390（1.088 ～ 1.775）] 和重度子痫前期[OR（95%CI）：1.589（1.222 ～ 2.066）] 是不良妊娠结局危险因素（均P<0.05）。血清lncRNA HIF1A-AS1，CXCL9 及指标联合预测子痫前期不良妊娠结局的AUC 分别为0.770，0.767 和0.876，指标联合预测价值优于单一指标，差异具有统计学意义（Z=2.455，2.398，均P<0.05）。结论 子痫前期患者血清lncRNA HIF1A-AS1 表达下调，CXCL9 表达上调，两指标与病情严重程度及不良妊娠结局有关，早期联合检测有望成为预测子痫前期患者不良妊娠结局的标志物。
Abstract:
Objective To explore the relationship between serum long non-coding RNA hypoxia-inducible factor 1 alpha antisense RNA 1 (lncRNA HIFA1-AS1)，CXC chemokine ligand 9 (CXCL9) and disease severity, adverse pregnancy outcome in patients with preeclampsia. Methods A total of 83 patients with preeclampsia admitted to Xi'an Gaoxin Hospital January 2021 to December 2022 were taken as preeclampsia group, According to the time of diagnosis, patients with preeclampsia were divided into early onset preeclampsia group (n=39) and late onset preeclampsia group (n=44). According to the severity of the condition, patients with preeclampsia were divided into two groups: mild preeclampsia group (n=51) and severe preeclampsia group (n=32). According to pregnancy outcomes, they were divided into a normal pregnancy outcome group (n=56) and an adverse pregnancy outcome group (n=27).At the same time, 60 healthy pregnant women with pregnancy were collected as control group. Real-time fluorescence quantitative PC(qRT-PCR) was used to detect serum lncRNA HIF1A-AS1, and enzymelinked immunosorbent assay(ELISA) was used to detect serum CXCL9. Spearman rank correlation analysis was used to analyze the association between serum lncRNA HIF1A-AS1, CXCL9 and severity of disease. Logistic regression analysis was used to analyze the factors influencing the adverse pregnancy outcome in patients with preeclampsia. ROC curve was drawn to assess the predictive value of serum lncRNA HIF1A-AS1, CXCL9 for adverse pregnancy outcome. Results The relative expression of serum lncRNA HIF1A-AS1 (0.73±0.26) in preeclampsia group was lower than that (1.15±0.34) in control group, and CXCL9 level (209.34±45.34 pg/ml) higher than that (116.80±37.76 pg/ml) in control group, the differences were statistically significant (t=8.379, 12.903, all P<0.05). The relative expression of serum lncRNA HIF1A-AS1 (0.58±0.21) in early-onset preeclampsia group was lower than that in late-onset preeclampsia group (0.86±0.27), and CXCL9 level (236.60±31.02 pg/ml) higher than that in late-onset preeclampsia group (185.18±23.63 pg/ml), the differences were statistically significant (t=5.226, 8.551, all P<0.05). The relative expression of serum lncRNA HIF1A-AS1 (0.52±0.21) in severe preeclampsia group was lower than that in late-onset preeclampsia group(0.97±0.34), and CXCL9 level (253.38±41.20 pg/ml) higher than that in late-onset preeclampsia group (159.65±40.79 pg/ml), the differences were statistically significant (t=6.409, 10.152, all P<0.05). Serum lncRNA HIF1AAS1 and CXCL9 were associated with condition of preeclampsia (r =-0.627, 0.651, all P<0.05). CXCL9 [OR (95%CI): 1.581 (1.098 ～ 2.276)] was independent risk factor for adverse pregnancy outcome in patients with preeclampsia (P<0.05). LncRNA HIF1A-AS1 [OR (95%CI): 0.806 (0.673 ～ 0.965)] was a protective factor (P<0.05), and early-onset preeclampsia [OR (95%CI): 1.390(1.088 ～ 1.775)] and severe preeclampsia [OR (95%CI): 1.589 (1.222 ～ 2.066)] were risk factors for adverse pregnancy outcome (all P<0.05). Serum lncRNA HIF1A-AS1, CXCL9 and indicators combined had predictive value for adverse pregnancy outcome in patients with preeclampsia, with AUC of 0.770, 0.767 and 0.876, respectively. And the combined prediction AUC was better than single indicator , and differences were statistically significant(Z=2.455, 2.398, all P<0.05). Conclusion Serum lncRNA HIF1A-AS1 expression is down-regulated and CXCL9 expression is up-regulated in patients with preeclampsia, both indicators are associated with severity of disease and adverse pregnancy outcome. Early detection of two indicators are expected to be markers for predicting adverse pregnancy outcome in patients with preeclampsia.

参考文献/References:

[1] 王晶, 王培萍, 张婕, 等. 血清及胎盘中Siglec-6,Glycodelin-A 水平与子痫前期发病和妊娠结局的相关性[J]. 中国生育健康杂志, 2023, 34(6): 567-570, 封3. WANG Jing, WANG Peiping, ZHANG Jie, et al. Correlation between Siglec-6 and Glycodelin-A levels in serum and placenta and the onset of preeclampsia and pregnancy outcomes [J]. Chinese Journal of Reproductive Health, 2023, 34(6): 567-570, F0003.
[2] TITA A T, SZYCHOWSKI J M, BOGGESS K, et al. Treatment for mild chronic hypertension during pregnancy[J]. New England Journal of Medicine, 2022,386(19): 1781-1792.
[3] 王芬, 陈媛, 谢环. 孕妇血清Collectrin 和NEP 表达水平与子痫前期的相关性研究[J]. 现代检验医学杂志, 2022, 37(6): 183-187. WANG Fen, CHEN Yuan, XIE Huan. Correlation of serum collectrin and NEP expression levels in pregnant women with pre-eclampsia[J]. Journal of Modern Laboratory Medicine, 2022, 37(6): 183-187.
[4] DECARLO C, BOITANO L T, MOLINA R L, et al. Pregnancy and preeclampsia are associated with acute adverse peripheral arterial events[J]. Arteriosclerosis,Thrombosis, and Vascular Biology, 2021, 41(1): 526-533.
[5] SUN Ningxia, CHEN Huaiyan, MA Yan, et al. H3K4me3-mediated upregulation of lncRNA-HEIPP in preeclampsia placenta affects invasion of trophoblast cells [J]. Frontiers in Genetics, 2020, 11: 559478.
[6] 肖宁, 林玮键, 龙永福. 长链非编码RNA HIF1AAS1的研究现状与进展[J]. 现代医学与健康研究电子杂志, 2021, 5(8): 126-128. XIAO Ning, LIN Weijian, LONG Yongfu. Current status and progress of research on long-stranded noncoding RNA HIF1A-AS1[J]. Modern Medicine and Health Research, 2021, 5(8): 126-128.
[7] XUE Xiang, LUO Libo. Statment of Retraction: lncRNA HIF1A-AS1 contributes to ventricular remodeling after myocardial ischemia/reperfusion injury by adsorption of microRNA-204 to regulating SOCS2 expression[J]. Cell Cycle, 2022, 21(7): 756.
[8] PAN Minjie, WEI Xiaoshan, XIANG Xuan, et al. Targeting CXCL9/10/11-CXCR3 axis: an important component of tumor-promoting and antitumor immunity[J]. Clinical & Translational Oncology, 2023,25(8): 2306-2320.
[9] SHAMSI A, ROGHANI S A, ABDAN Z, et al. CXCL9 and its receptor CXCR3, an important link between inflammation and cardiovascular risks in RA patients[J]. Inflammation, 2023, 46(6): 2374-2385.
[10] 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. Hypertensive Disorders in Pregnancy Subgroup,Chinese Society of Obstetrics and Gynecology, Chinese Medical Association. Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China(2020)[J]. Chinese Journal of Obstetrics and Gynecology, 2020, 55(4): 227-238.
[11] JUNG E, ROMERO R, YEO L M, et al. The etiology of preeclampsia[J]. American Journal of Obstetrics and Gynecology, 2022, 226(2S): S844-S866.
[12] YANG Yingying, LE RAY I, ZHU Jing, et al. Preeclampsia prevalence, risk factors, and pregnancy outcomes in Sweden and China[J]. JAMA Netw Open,2021, 4(5): e218401.
[13] ARDISSINO M, REDDY R K, SLOB E A W, et al. Maternal hypertensive traits and adverse outcome in pregnancy: a Mendelian randomization study[J]. Journal of Hypertension, 2023, 41(9): 1438-1445.
[14] JAHAN F, VASAM G, GREEN A E , e t a l . Placental mitochondrial function and dysfunction in preeclampsia[J]. International Journal of Molecular Sciences, 2023, 24(4): 4177.
[15] MINOPOLI M, NO?L L, MERONI A, et al. Adverse pregnancy outcomes in women at increased risk of preterm pre-eclampsia on first-trimester combined screening [J]. BJOG, 2024, 131(1): 81-87.
[16] XU Xun, LIANG Yuan, GAREEV I, et al. LncRNA as potential biomarker and therapeutic target in glioma[J]. Molecular Biology Reports, 2023, 50(1): 841-851.
[17] PULIK ?, MIERZEJEWSKI B, SIBILSKA A, et al. The role of miRNA and lncRNA in heterotopic ossification pathogenesis[J]. Stem Cell Research & Therapy, 2022, 13(1): 523.
[18] YANG Yanlin, SHANG Haixia. Silencing lncRNADGCR5 increased trophoblast cell migration, invasion and tube formation, and inhibited cell apoptosis via targeting miR-454-3p/GADD45A axis[J]. Molecular and Cellular Biochemistry, 2021, 476(9): 3407-3421.
[19] 赵丹, 安杰, 刘倩, 等. LncRNA RPAIN 在子痫前期患者胎盘组织中的表达及对滋养细胞增殖和侵袭的影响[J]. 临床误诊误治, 2021, 34(12): 34-39. ZHAO Dan, AN Jie, LIU Qian, et al. Expression of long non-coding RNA RPAIN in placenta tissues of patients with preeclampsia and its effects on proliferation and invasion of trophoblast cells[J]. Clinical Misdiagnosis & Mistherapy, 2021, 34(12): 34-39.
[20] 李勤, 许娟秀, 尧旋. LncRNA HIF1A-AS2 通过抑制miR-138-5p 促进滋养层细胞的侵袭和上皮间充质转化[J]. 第三军医大学学报, 2020, 42(22): 2210-2218. LI Qin, XU Juanxiu, YAO Xuan. LncRNA HIF1AAS2 promotes trophoblast invasion and epithelialmesenchymal transformation by inhibiting miR-138-Sp[J]. Journal of Third Military Medical University,2020, 42(22): 2210-2218.
[21] 霍春霞, 谢玲, 张爱萍. 青海地区子痫前期孕妇lncRNA HIF1A-AS1 的表达及临床意义[J]. 中国优生与遗传杂志, 2023, 31(10): 2171-2174. HUO Chunxia, XIE Ling, ZHANG Aiping. Expression and clinical significance of lncRNA HIF1A-AS1 in pregnant women with preeclampsia in Qinghai area[J]. Chinese Journal of Birth Health & Heredity, 2023,31(10): 2171-2174.
[22] ZHENG Yan, ZHENG Yunfei, JIA Lingfei, et al. Integrated analysis of lncRNA-mRNA networks associated with an SLA titanium surface reveals the potential role of HIF1A-AS1 in bone remodeling[J]. RSC Advances, 2020, 10(35): 20972-20990.
[23] YANG Jin, GONG Zhiqiang, DONG Junjie, et al. Transcriptomics provides novel insights into the regulatory mechanism of lncRNA HIF1 A-AS1 on vascular smooth muscle cells[J]. Brazilian Journal Cardiovascular Surgery, 2023, 38(6): e20220260.
[24] ZHOU Huan, WANG Bin, YANG Yingxi, et al. Long noncoding RNAs in pathological cardiac remodeling: a review of the update literature [J]. BioMed Research International, 2019, 2019: 7159592.
[25] ZHOU Chenjia, GAO Ying, DING Peilun, et al. The role of CXCL family members in different diseases[J]. Cell Death Discovery, 2023, 9(1): 212.
[26] LIU Hanqing, WANG Yihui, LE Qianqian, et al. The IFN-γ-CXCL9/CXCL10-CXCR3 axis in vitiligo: pathological mechanism and treatment [J]. Immunoloy,2024,54(4):e2250281.
[27] 杨罡, 赵峻, 张云辉. CXC 型趋化因子及其受体轴在慢性阻塞性肺疾病中的研究进展[J]. 中国呼吸与危重监护杂志, 2021, 20(10): 748-752. YANG Gang, ZHAO Jun, ZHANG Yunhui. CXC-type chemokine and their receptor axis in chronic obstructive lung disease[J]. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(10): 748-752.
[28] 王芙蓉, 严谨, 贺丰杰. 子痫前期患者及其胎儿血清?胎盘组织中趋化因子的表达水平变化及意义[J].中国生育健康杂志, 2022, 33(2): 151-155. WANG Furong, YAN Jin, HE Fengjie. Changes and significance of chemokine expression level in serum and placental tissues of patients with preeclampsia and their fetuses[J]. Chinese Journal of Reproductive Health, 2022, 33(2): 151-155.

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备注/Memo

备注/Memo:
基金项目：陕西省科技计划项目（编号：2020SF-344）。
作者简介：张金辉（1987-），女，本科，主治医师，研究方向：妇产科，E-mail：zhangjhui256425@163.com。
通讯作者：闫璐（1985-），女，本科，主治医师，研究方向：妇产科，E-mail：302015496@qq.com。
更新日期/Last Update: 2024-11-15