子痫前期患者的胎盘环状RNA表达谱及与病情的相关性

doi:10.11958/20221313

天津医药 ›› 2023, Vol. 51 ›› Issue (5): 513-517.doi: 10.11958/20221313

子痫前期患者的胎盘环状RNA表达谱及与病情的相关性

韩贞艳(), 关红琼^△()

海南医学院第二附属医院产科（邮编570311）

收稿日期:2022-08-22 修回日期:2022-12-05 出版日期:2023-05-15 发布日期:2023-05-05
通讯作者: △E-mail:guanhq1962@163.com
作者简介:韩贞艳（1980），女，副主任医师，主要从事产科疾病的诊治方面研究。E-mail：dashingt@163.com
基金资助:
海南省卫生健康行业科研项目(20A200470)

The expression profile of circular RNA in placenta of patients with preeclampsia and its correlation with the patient’s condition

HAN Zhenyan(), GUAN Hongqiong^△()

Department of Obstetrics, Second Affiliated Hospital of Hainan Medical College, Haikou 570311, China

Received:2022-08-22 Revised:2022-12-05 Published:2023-05-15 Online:2023-05-05
Contact: △E-mail:guanhq1962@163.com

韩贞艳, 关红琼. 子痫前期患者的胎盘环状RNA表达谱及与病情的相关性[J]. 天津医药, 2023, 51(5): 513-517.

HAN Zhenyan, GUAN Hongqiong. The expression profile of circular RNA in placenta of patients with preeclampsia and its correlation with the patient’s condition[J]. Tianjin Medical Journal, 2023, 51(5): 513-517.

摘要/Abstract

摘要：

目的分析子痫前期患者胎盘环状RNA（circRNA）表达谱基因表达情况及其与患者病情的相关性。方法选取子痫前期患者（子痫前期组）15例，重度子痫前期患者（重度子痫前期组）25例及正常妊娠女性（对照组）30例。收集患者临床资料，检测各组24 h尿蛋白定量；采用酶联免疫吸附试验检测血清中的STOX1蛋白、血清可溶性血管内皮生长因子受体1（sFlt-1）、胎盘生长因子（PLGF）及血管内皮生长因子（VEGF）水平。于胎盘娩出后收集胎盘组织，检测胎盘circRNA表达情况，选取上调及下调基因各自差异表达水平由高到低排名前3位的基因进行分析；分析孕妇差异表达基因与24 h尿蛋白定量、平均动脉压、STOX1、sFlt-1、PLGF和VEGF的相关性；采用多元线性回归模型分析影响孕妇24 h尿蛋白定量的相关因素。结果与对照组比较，子痫前期组及重度子痫前期组的孕前体质量指数和平均动脉压升高（P<0.05）；对照组、子痫前期组及重度子痫前期组24 h尿蛋白定量、STOX1、sFlt-1、胎盘hsa_circ_0014736、hsa_circ_0015383及hsa_circ_0004904表达水平依次升高，而hsa_circ_0063517、hsa_circ_0007121及hsa_circ_0003171表达水平依次降低（P<0.05）；子痫前期组及重度子痫前期组hsa_circ_0014736、hsa_circ_0015383及hsa_circ_0004904分别与BMI、平均动脉压、24 h尿蛋白定量、STOX1、sFlt-1呈正相关，与VEGF、PLGF呈负相关（P<0.05），而hsa_circ_0063517、hsa_circ_0007121及hsa_circ_0003171与临床特征的相关性与此相反（P<0.05）。多元线性回归分析显示，hsa_circ_0015383与孕妇24 h尿蛋白定量呈正向线性相关，hsa_circ_0063517及hsa_circ_0007121与孕妇24 h尿蛋白定量呈负向线性相关（P<0.05）。结论子痫前期孕妇胎盘中hsa_circ_0063517及hsa_circ_0007121表达水平下调，hsa_circ_0015383表达水平上调，与患者病情密切相关。

关键词: 先兆子痫, 胎盘, RNA,环状, 血管内皮生长因子受体-1, 胎盘生长因子, 血管内皮生长因子, 24 h尿蛋白定量

Abstract:

Objective To analyze expression profile of circular RNA (circRNA) in placenta of patients with preeclampsia and its correlation with the patients' condition. Methods A total of 15 patients with preeclampsia (the preeclampsia group), 25 patients with severe preeclampsia (the severe preeclampsia group), and 30 normal pregnant women (the control group) were selected. Clinical data of patients were collected. 24 h urinary protein levels were detected in each group. Serum STOX1 protein, serum soluble vascular endothelial growth factor receptor 1 (sFlt-1), placental growth factor (PLGF) and vascular endothelial growth factor (VEGF) were detected by enzyme-linked immunosorbent assay. The placental samples were collected after delivery, and the expression of circRNA in placenta was detected. The top three genes with differentially expressed levels of up-regulated and down-regulated genes from high to low were selected for analysis. The correlation of differentially expressed genes with 24 h urinary protein, mean arterial pressure, STOX1, sFlt-1, PLGF and VEGF in pregnant women was analyzed. Multiple linear regression model was used to analyze factors affecting the quantitative level of 24 h urine protein in pregnant women. Results Compared with the control group, there were higher prepregnancy body mass index and mean arterial pressure in the preeclampsia group and the severe preeclampsia group (P<0.05). The 24 h urinary protein quantity, STOX1, sFlt-1, hsa_circ_0014736, hsa_circ_0015383 and hsa_circ_0004904 expression levels in placenta were increased gradually in the control group, the preeclampsia group and the severe preeclampsia group. The expression levels of hsa_circ_0063517, hsa_circ_0007121 and hsa_circ_0003171 were decreased gradually (P<0.05). Values of hsa_circ_0014736, hsa_circ_0015383 and hsa_circ_0004904 were positively correlated with mean arterial pressure, 24 h urinary protein quantity, STOX1 and sFlt-1 in the preeclampsia group and the severe preeclampsia group respectively. They were negatively correlated with VEGF and PLGF (P<0.05), while hsa_circ_0063517, hsa_circ_0007121 and hsa_circ_0003171 were negatively correlated with clinical features (P<0.05). Multiple linear regression analysis showed that hsa_circ_0015383 had positive linear correlation with 24 h urinary protein quantification in pregnant women, and hsa_circ_0063517 and hsa_circ_0007121 had negative linear correlation with 24 h urinary protein quantification in pregnant women (P<0.05). Conclusion The expression levels of hsa_circ_0063517 and hsa_circ_0007121 in placenta are down-regulated in preeclampsia pregnant women, and expression levels of hsa_circ_0015383 are up-regulated, which is closely related to the patient's condition.

Key words: pre-eclampsia, placenta, RNA, circular, vascular endothelial growth factor receptor-1, placenta growth factor, vascular endothelial growth factors, 24 h urine protein quantification

中图分类号:

R446.8

图/表 5

参考文献 18

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组别	n	年龄（岁）	孕次（次）	产次		孕周（周）	BMI （kg/m²）	平均动脉压（mmHg）
组别	n	年龄（岁）	孕次（次）	初产妇	经产妇	孕周（周）	BMI （kg/m²）	平均动脉压（mmHg）
对照组	30	28.01±4.53	1.28±0.37	13	17	33.91±3.25	23.78±2.36	95.01±3.76
子痫前期组	15	28.68±4.98	1.45±0.36	4	11	32.98±2.97	25.36±2.54^a	100.83±6.72^a
重度子痫前期组	25	27.39±4.45	1.43±0.41	9	16	33.14±3.02	25.89±3.36^a	106.78±8.46^ab
F或χ²		0.376	1.464	1.212		0.622	4.181^＊	22.961^＊＊

组别	n	年龄（岁）	孕次（次）	产次		孕周（周）	BMI （kg/m²）	平均动脉压（mmHg）
组别	n	年龄（岁）	孕次（次）	初产妇	经产妇	孕周（周）	BMI （kg/m²）	平均动脉压（mmHg）
对照组	30	28.01±4.53	1.28±0.37	13	17	33.91±3.25	23.78±2.36	95.01±3.76
子痫前期组	15	28.68±4.98	1.45±0.36	4	11	32.98±2.97	25.36±2.54^a	100.83±6.72^a
重度子痫前期组	25	27.39±4.45	1.43±0.41	9	16	33.14±3.02	25.89±3.36^a	106.78±8.46^ab
F或χ²		0.376	1.464	1.212		0.622	4.181^＊	22.961^＊＊

组别	n	24 h尿蛋白定量（g）	STOX1（ng/L）	sFlt-1（ng/L）	VEGF（ng/L）	PLGF（pg/L）
对照组	30	0.09±0.01	40.67±5.13	203.54±65.28	232.73±25.76	511.23±79.21
子痫前期组	15	1.28±0.33^a	44.39±6.28^a	255.82±71.34^a	187.12±20.89^a	461.54±62.79^a
重度子痫前期组	25	4.43±1.21^ab	49.41±7.39^ab	298.42±79.48^ab	151.37±18.26^ab	413.64±53.02^ab
F		241.269^＊＊	13.298^＊＊	11.966^＊＊	91.537^＊＊	14.319^＊＊

组别	n	24 h尿蛋白定量（g）	STOX1（ng/L）	sFlt-1（ng/L）	VEGF（ng/L）	PLGF（pg/L）
对照组	30	0.09±0.01	40.67±5.13	203.54±65.28	232.73±25.76	511.23±79.21
子痫前期组	15	1.28±0.33^a	44.39±6.28^a	255.82±71.34^a	187.12±20.89^a	461.54±62.79^a
重度子痫前期组	25	4.43±1.21^ab	49.41±7.39^ab	298.42±79.48^ab	151.37±18.26^ab	413.64±53.02^ab
F		241.269^＊＊	13.298^＊＊	11.966^＊＊	91.537^＊＊	14.319^＊＊

组别	n	hsa_circ_0014736	hsa_circ_0015383	hsa_circ_0004904	hsa_circ_0063517	hsa_circ_0007121	hsa_circ_0003171
对照组	30	0.81±0.15	0.83±0.17	0.87±0.23	1.07±0.23	1.21±0.19	1.19±0.23
子痫前期组	15	1.13±0.17^a	1.02±0.19^a	1.12±0.27^a	0.87±0.16^a	0.76±0.15^a	1.01±0.18^a
重度子痫前期组	25	1.53±0.19^ab	1.48±0.23^ab	1.33±0.34^ab	0.72±0.11^ab	0.43±0.12^ab	0.89±0.17^ab
F		123.127^＊＊	75.541^＊＊	18.263^＊＊	25.938^＊＊	164.876^＊＊	15.614^＊＊

子痫前期患者的胎盘环状RNA表达谱及与病情的相关性

The expression profile of circular RNA in placenta of patients with preeclampsia and its correlation with the patient’s condition

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因素	B	SE	β	t	P
BMI	-0.008	0.039	-0.011	-0.207	0.837
平均动脉压	-0.002	0.017	-0.007	-0.102	0.919
sFlt-1	0.033	0.017	0.111	1.969	0.055
STOX1	0.002	0.001	0.063	1.081	0.285
VEGF	0.005	0.005	0.076	1.118	0.269
PLGF	0.002	0.002	0.060	1.033	0.307
hsa_circ_0063517	-1.334	0.513	-0.183	-2.599	0.012
hsa_circ_0007121	-1.468	0.626	-0.267	-2.346	0.023
hsa_circ_0003171	-0.481	0.536	-0.060	-0.897	0.374
hsa_circ_0014736	0.580	0.576	0.107	1.006	0.320
hsa_circ_0015383	2.057	0.393	0.406	5.233	<0.001
hsa_circ_0004904	0.529	0.341	0.094	1.552	0.127
常数项	-2.113	3.339	-	-0.633	0.530

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