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miR-3064-5p和miR-4745-5p通过调节抗凝血酶III(AT-III)和凝血因子X的mRNA水平影响心脏手术患者的肝素敏感性。

miR-3064-5p and miR-4745-5p affect heparin sensitivity in patients undergoing cardiac surgery by regulating AT-III and factor X mRNA levels.

作者信息

Ma Hai-Ping, Fu Min, Masula Maisitanguli, Xing Chang-Shuang, Zhou Qiang, Tan Jing-Tong, Wang Jiang

机构信息

The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

出版信息

Front Physiol. 2022 Aug 12;13:914333. doi: 10.3389/fphys.2022.914333. eCollection 2022.

Abstract

Perioperative regulation of coagulation function through heparin in patients undergoing cardiac surgery with cardiopulmonary bypass is an important part of performing cardiac surgery, and postoperative bleeding due to abnormal coagulation function caused by differences in heparin sensitivity in different individuals is an independent risk factor for postoperative complications and death. Using an online database, 10 miRNAs interacting with AT-III and FX genes were predicted. Patients were divided into three groups according to the difference in activated clotting time (ACT) after the first dose of heparin (2.5 mg kg): group A: hyposensitive group (ACT < 480 s); group B: sensitive group (480 s ≤ ACT ≤ 760 s); and group C: hypersensitive group (ACT > 760 s). Perioperative and 24 h postoperative blood loss and other clinical data of patients in the three groups were recorded. Blood samples were collected before surgery, and RT-PCR was used to detect the levels of AT-III and FX gene mRNA and the levels of predicted 10 miRNAs. Heparin sensitivity was positively correlated with AT-III mRNA levels and negatively correlated with FX gene mRNA levels in the three groups, and the blood loss in group B was significantly lower than that in groups A and C, which was statistically significant ( < 0.05). miR-3064-5p and miR-4745-5p expression levels were significantly different among group A, group B, and group C ( < 0.05) and were closely correlated with AT-III and FX gene mRNA expression levels, respectively. Differences in heparin sensitivity in patients undergoing cardiac surgery were associated with the mRNA expression of AT-III and FX genes, and the expression levels of miR-3064-5p and miR-4745-5p were found to be closely related to the AT-III and FX gene mRNA, respectively, indicating that miR-3064-5p and miR-4745-5p affect the differences in heparin sensitivity among different individuals by regulating the mRNA expression levels of AT-III and FX genes. http://www.chictr.org.cn/abouten.aspx, identifier registration number: ChiCTR-2100047348.

摘要

在接受体外循环心脏手术的患者中,通过肝素进行围手术期凝血功能调节是心脏手术操作的重要组成部分,并且由于不同个体肝素敏感性差异导致的凝血功能异常引起的术后出血是术后并发症和死亡的独立危险因素。利用在线数据库,预测了10种与抗凝血酶III(AT-III)和凝血因子X(FX)基因相互作用的微小RNA(miRNA)。根据首次给予肝素(2.5mg/kg)后活化凝血时间(ACT)的差异将患者分为三组:A组:低敏组(ACT<480秒);B组:敏感组(480秒≤ACT≤760秒);C组:高敏组(ACT>760秒)。记录三组患者围手术期及术后24小时的失血量等临床资料。术前采集血样,采用逆转录-聚合酶链反应(RT-PCR)检测AT-III和FX基因mRNA水平以及预测的10种miRNA的水平。三组中肝素敏感性与AT-III mRNA水平呈正相关,与FX基因mRNA水平呈负相关,且B组失血量显著低于A组和C组,差异有统计学意义(P<0.05)。A组、B组和C组之间miR-3064-5p和miR-4745-5p表达水平差异有统计学意义(P<0.05),且分别与AT-III和FX基因mRNA表达水平密切相关。心脏手术患者肝素敏感性的差异与AT-III和FX基因的mRNA表达有关,且发现miR-3064-5p和miR-4745-5p的表达水平分别与AT-III和FX基因mRNA密切相关,表明miR-3064-5p和miR-4745-5p通过调节AT-III和FX基因的mRNA表达水平影响不同个体之间肝素敏感性的差异。http://www.chictr.org.cn/abouten.aspx,标识符注册号:ChiCTR-2100047348。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c3/9412912/4bd6ca483c30/fphys-13-914333-g001.jpg

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