Department of Interventional Medicine, The Affiliated Hospital of Binzhou Medical University, Binzhou, P.R. China.
Department of Vasculocardiology, The Affiliated Hospital of Binzhou Medical University, Binzhou, P.R. China.
J Cell Biochem. 2018 Jul;119(7):5262-5273. doi: 10.1002/jcb.26633. Epub 2018 Mar 12.
This study aims to elucidate the prognostic and predictive biomarker of miR-495 and Stat3 in peripheral blood in relation to lower extremity deep venous thrombosis (DVT). Patients with lower limb fractures were assigned into case and control groups. Rats were allocated into blank (normal rats), sham (normal rats), DVT, miR-495 mimic, miR-495 inhibitor, over-Stat3, and si-Stat3 groups. ELISA was used to detect levels of prothrombin time (PT), endothelin-1 (ET-1), Human Fibrinogen (FIB), D-Dimer, blood coagulation factors V and VIII, tissue type plasminogen activator (t-PA), platelet activating factor (PAF), protein C and Stat3. qRT-PCR was employed for the evaluation of the expressions of miR-495 and Stat3, while receiver operating characteristic (ROC) curve was constructed to assess the predictive value of miR-495 and Stat3 as well as the treatment outcomes of patients with lower limb fractures. Logistic regression analyses were conducted in order to correlate indexes and lower extremity DVT. miR-495 overexpression, t-PA, PAF, and protein C were confirmed to be protective factors, while Stat3 overexpression, PT, ET-1, FIB, D-Dimer, blood coagulation factor V, and VIII were all ultimately considered to be risk factors of lower extremity DVT. Stat3 was confirmed to be the target gene of miR-495. Compared with the blank group, the length and weight of the thrombus as well as the ratio between length and weight, mRNA and protein expression of Stat3 were reduced in the miR-495 mimic and si-Stat3 groups. Our findings suggest that through the suppression of Stat3 expression, miR-495 prohibits lower extremity DVT in peripheral blood.
本研究旨在阐明外周血 miR-495 和 Stat3 与下肢深静脉血栓形成（DVT）的预后和预测生物标志物。将下肢骨折患者分为病例组和对照组。将大鼠分为空白（正常大鼠）、假手术（正常大鼠）、DVT、miR-495 模拟物、miR-495 抑制剂、过表达 Stat3 和 si-Stat3 组。ELISA 用于检测凝血酶原时间（PT）、内皮素-1（ET-1）、人纤维蛋白原（FIB）、D-二聚体、凝血因子 V 和 VIII、组织型纤溶酶原激活物（t-PA）、血小板激活因子（PAF）、蛋白 C 和 Stat3 的水平。qRT-PCR 用于评估 miR-495 和 Stat3 的表达，而接收者操作特征（ROC）曲线用于评估 miR-495 和 Stat3 的预测价值以及下肢骨折患者的治疗结果。Logistic 回归分析用于关联指标和下肢 DVT。miR-495 过表达、t-PA、PAF 和蛋白 C 被证实是保护因素，而 Stat3 过表达、PT、ET-1、FIB、D-二聚体、凝血因子 V 和 VIII 最终被认为是下肢 DVT 的危险因素。Stat3 被证实是 miR-495 的靶基因。与空白组相比，miR-495 模拟物和 si-Stat3 组 Stat3 的 mRNA 和蛋白表达减少，血栓长度和重量以及长度与重量之比均降低。我们的研究结果表明，通过抑制 Stat3 表达，miR-495 可防止外周血中的下肢 DVT。
