血清miR-181b及miR-210在妊娠期高血压疾病中表达及与炎性细胞因子的相关性
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摘要
目的探讨妊娠期高血压疾病(hypertensive disorders in pregnancy, HDP)患者血清miR-181b、miR-210表达变化,分析其与白细胞介素(interleukin, IL)-1β、IL-6及肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)的关系。方法 HDP患者226例,其中妊娠期高血压(gestational hypertension, GH)60例(GH组)、轻度子痫前期(mild preeclampsia, MP)90例(MP组)、重度子痫前期(servere preeclampsia, SP)76例(SP组),同期健康孕妇60例为对照组。检测4组血清miR-181b mRNA、miR-210 mRNA相对表达量及IL-1β、IL-6及TNF-α水平;Pearson相关分析HDP患者血清miR-181b mRNA、miR-210 mRNA相对表达量与IL-1β、IL-6及TNF-α的相关性。结果对照组、GH、MP、SP组血清miR-181b mRNA相对表达量(1.42±0.65、5.73±1.60、10.94±4.28、17.13±8.16)、miR-210 mRNA相对表达量(0.84±0.13、3.62±1.05、4.74±1.36、7.92±2.17),IL-1β[(2.60±0.84)、(11.26±2.53)、(17.65±6.24)、(23.92±9.16)ng/L]、IL-6[(90.26±27.45)、(106.35±33.74)、(128.42±36.18)、(151.46±40.27)ng/L]及TNF-α[(12.40±2.28)、(19.25±4.42)、(35.84±6.53)、(64.73±9.50)ng/L]水平依次增高(P<0.05);HDP患者血清miR-181b mRNA相对表达量与IL-1β、IL-6、TNF-α呈正相关(r=0.694,P<0.001;r=0.735,P<0.001;r=0.846,P<0.001)、miR-210 mRNA相对表达量与IL-1β、IL-6、TNF-α呈正相关(r=0.548,P=0.003;r=0.718,P<0.001;r=0.815,P<0.001)。结论 HDP患者miR-181b及miR-210表达上调,且上调程度与HDP病情严重程度及IL-1β、IL-6、TNF-α水平变化相关,可能参与HDP的发生、发展。
Objective To investigate the expressions of serum miR-181b and miR-210 in patients with hypertensive disorders in pregnancy(HDP), and their correlations with interleukin(IL)-1β, IL-6 and tumor necrosis factor-α(TNF-α). Methods Totally 226 patients with HDP were divided into 60 patients with gestational hypertension(GH group), 90 patients with mild preeclampsia(MP group) and 76 patients with severe preeclampsia(SP group), and another 60 healthy pregnant women in the same period were selected as control group. The relative expressions of serum miR-181b mRNA and miR-210 mRNA as well as the levels of IL-1β, IL-6 and TNF-α were detected in four groups. Pearson correlation method was used to analyze the correlation of serum miR-181b mRNA and miR-210 mRNA levels with IL-1β, IL-6 and TNF-α in HDP patients. Results The relative expressions of serum miR-181b mRNA(1.42±0.65, 5.73±1.60, 10.94±4.28, 17.13±8.16), miR-210 mRNA(0.84±0.13, 3.62±1.05, 4.74±1.36, 7.92±2.17), IL-1β((2.60±0.84),(11.26±2.53),(17.65±6.24),(23.92±9.16) ng/L), IL-6((90.26±27.45),(106.35±33.74),(128.42±36.18),(151.46±40.27) ng/L) and TNF-α((12.40±2.28),(19.25±4.42),(35.84±6.53),(64.73±9.50) ng/L) increased gradually in control group, GH group, MP group and SP group in turns(P<0.05). The relative expression of serum miR-181b mRNA was positively correlated with IL-1β, IL-6 and TNF-α in HDP patients(r=0.694, P<0.001; r=0.735, P<0.001; r=0.846, P<0.001), and the relative expression of miR-210 mRNA was positively correlated with IL-1β,IL-6 and TNF-α(r=0.548,P=0.003;r=0.718,P<0.001;r=0.815,P<0.001).Conclusion The expressions of serum miR-181b and miR-210 are up-regulated in HDP patients along with the severity of HDP as well as the changes of IL-1β,IL-6 and TNF-αlevels,and might be involved in the occurrence and development of HDP.
Objective To investigate the expressions of serum miR-181b and miR-210 in patients with hypertensive disorders in pregnancy(HDP), and their correlations with interleukin(IL)-1β, IL-6 and tumor necrosis factor-α(TNF-α). Methods Totally 226 patients with HDP were divided into 60 patients with gestational hypertension(GH group), 90 patients with mild preeclampsia(MP group) and 76 patients with severe preeclampsia(SP group), and another 60 healthy pregnant women in the same period were selected as control group. The relative expressions of serum miR-181b mRNA and miR-210 mRNA as well as the levels of IL-1β, IL-6 and TNF-α were detected in four groups. Pearson correlation method was used to analyze the correlation of serum miR-181b mRNA and miR-210 mRNA levels with IL-1β, IL-6 and TNF-α in HDP patients. Results The relative expressions of serum miR-181b mRNA(1.42±0.65, 5.73±1.60, 10.94±4.28, 17.13±8.16), miR-210 mRNA(0.84±0.13, 3.62±1.05, 4.74±1.36, 7.92±2.17), IL-1β((2.60±0.84),(11.26±2.53),(17.65±6.24),(23.92±9.16) ng/L), IL-6((90.26±27.45),(106.35±33.74),(128.42±36.18),(151.46±40.27) ng/L) and TNF-α((12.40±2.28),(19.25±4.42),(35.84±6.53),(64.73±9.50) ng/L) increased gradually in control group, GH group, MP group and SP group in turns(P<0.05). The relative expression of serum miR-181b mRNA was positively correlated with IL-1β, IL-6 and TNF-α in HDP patients(r=0.694, P<0.001; r=0.735, P<0.001; r=0.846, P<0.001), and the relative expression of miR-210 mRNA was positively correlated with IL-1β,IL-6 and TNF-α(r=0.548,P=0.003;r=0.718,P<0.001;r=0.815,P<0.001).Conclusion The expressions of serum miR-181b and miR-210 are up-regulated in HDP patients along with the severity of HDP as well as the changes of IL-1β,IL-6 and TNF-αlevels,and might be involved in the occurrence and development of HDP.
引文
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[14] LI W, CUI N, MAZZUCA M Q, et al. Increased vascular and uteroplacental matrix metalloproteinase-1 and -7 levels and collagen type I deposition in hypertension in pregnancy: role of TNF-α[J]. Am J Physiol Heart Circ Physiol,2017,313(3):H491-H507.
[15] 叶海琼,傅晓冬.microRNA-19a在妊娠期高血压疾病孕妇外周血中的表达[J].中国计划生育和妇产科,2016,8(6):17-20.
[16] KALINDERIS M, PAPANIKOLAOU A, KALINDERI K, et al. Elevated serum levels of interleukin-6, interleukin-1β and human chorionic gonadotropin in pre-eclampsia[J]. Am J Reprod Immunol,2011,66(6):468-475.
[17] OZKAN Z S, SIMSEK M, ILHAN F, et al. Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia, and their relation with severity of disease[J]. J Matern Fetal Neonatal Med,2014,27(15):1513-1517.
[2] 柴玉琼,洪亮.妊娠高血压疾病母亲其新生儿发生脑损伤的高危因素[J].中华实用诊断与治疗杂志,2018,32(6):612-614.
[3] TAVAKKOL AFSHARI Z, RAHIMI H R, et al. Tumor necrosis factor-α and interleukin-1β polymorphisms in pre-eclampsia[J]. Iran J Immunol,2016,13(4):309-316.
[4] MOHSENI Z, SPAANDERMAN MEA, OBEN J, et al. Cardiac remodeling and pre-eclampsia: an overview of microRNA expression patterns[J]. Ultrasound Obstet Gynecol,2018,52(3):310-317.
[5] MUNAUT C, TEBACHE L, BLACHER S, et al. Dysregulated circulating miRNAs in preeclampsia[J]. Biomed Rep,2016,5(6):686-692.
[6] 谢幸,苟文丽.妇产科学[M].8版.北京:人民卫生出版社,2013:64-71.
[7] 余丹.miRNA在自闭症中研究进展[J].中华实用诊断与治疗杂志,2017,31(6):613-615.
[8] HERSHKOVITZ-ROKAH, GEVA P, SALMON-DIVON M, et al. Network analysis of microRNAs, genes and their regulation in diffuse and follicular B-cell lymphomas[J]. Oncotarget,2018,9(8):7928-7941.
[9] GU X, JIN R, MAO X, et al. Prognostic value of miRNA-181a/b in colorectal cancer: a meta-analysis[J]. Biomark Med,2018,12(3):299-308.
[10] QU Y, HUANG W. Effects of miR-210 on the diagnosis and treatment of prostate cancer[J]. Mol Med Rep,2018,18(2):1740-1744.
[11] MURPHY M S, TAYADE C, SMITH G N. Maternal circulating microRNAs and pre-eclampsia: challenges for diagnostic potential[J]. Mol Diagn Ther,2017,21(1):23-30.
[12] 李付军,李玉山.子痫前期患者血清中IL-6、TNF-α的表达[J].医药论坛杂志,2006,1(11):44-45.
[13] YOUNGSTEIN T, HOFFMANN P, GüL A, et al. International multi-centre study of pregnancy outcomes with interleukin-1 inhibitors[J]. Rheumatology (Oxford),2017,56(12):2102-2108.
[14] LI W, CUI N, MAZZUCA M Q, et al. Increased vascular and uteroplacental matrix metalloproteinase-1 and -7 levels and collagen type I deposition in hypertension in pregnancy: role of TNF-α[J]. Am J Physiol Heart Circ Physiol,2017,313(3):H491-H507.
[15] 叶海琼,傅晓冬.microRNA-19a在妊娠期高血压疾病孕妇外周血中的表达[J].中国计划生育和妇产科,2016,8(6):17-20.
[16] KALINDERIS M, PAPANIKOLAOU A, KALINDERI K, et al. Elevated serum levels of interleukin-6, interleukin-1β and human chorionic gonadotropin in pre-eclampsia[J]. Am J Reprod Immunol,2011,66(6):468-475.
[17] OZKAN Z S, SIMSEK M, ILHAN F, et al. Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia, and their relation with severity of disease[J]. J Matern Fetal Neonatal Med,2014,27(15):1513-1517.