目的 基于核转录因子-κB （NF-κB） p65信号通路探讨阿加曲班联合阿替普酶对急性缺血性脑卒中的疗效及对患者抑郁相关指标的影响。方法 前瞻性选取邢台市第三医院2019年11月—2020年6月收治的164例发病4.5 h之内的无溶栓禁忌的急性缺血性脑卒中患者为研究对象，患者随机分为对照组和试验组，每组82例。两组患者均给予阿替普酶静脉溶栓治疗，溶栓24 h后均给予硫酸氢氯吡格雷，试验组患者在对照组基础上于溶栓24 h后给予阿加曲班静脉滴注治疗，连续治疗4周。分别于治疗前、注射用阿替普酶溶栓治疗完成即刻、溶栓治疗结束3 h、溶栓治疗结束48 h测定两组患者的活化部分凝血活酶时间（APTT）水平。采用美国国立卫生研究院卒中量表（NIHSS）、汉密尔顿抑郁量表（HAMD）、简易智力状态检查量表（MMSE）、日常生活能力量表（ADL）对两组患者进行疗效评价。分别于治疗前及治疗后采用实时荧光定量PCR（qRT-PCR）检测两组患者血清NF-κB p-p65与p65、p-IκBα与IκBα的mRNA表达。治疗期间及治疗后，观察两组患者脑出血、血红蛋白下降（＜100 g·L^-1）、APTT延长（＞53 s）等并发症发生情况。结果 治疗前，两组患者APTT比较，差异不显著（P＞0.05）；与治疗前比较，溶栓治疗结束即刻和溶栓治疗结束3 h，两组患者APTT均显著延长（P＜0.05）；与治疗前比较，溶栓治疗结束48 h试验组APTT基本恢复正常，但对照组仍显著延长（P＜0.05）；相比于对照组，试验组的总有效率更高（P＜0.05）；与对照组比较，治疗后，试验组血红蛋白下降以及APTT延长发生例数略低于对照组，但差异无统计学意义（P＞0.05）；治疗前，两组患者NIHSS、HAMD、MMSE、ADL评分比较，差异均无统计学意义（P＞0.05）；治疗1周以及4周后，对照组和试验组NIHSS、HAMD评分显著降低（P＜0.05），且试验组患者的NIHSS、HAMD评分低于对照组（P＜0.05），同时MMSE、ADL评分显著升高（P＜0.05），且试验组患者的MMSE、ADL评分高于对照组（P＜0.05）；治疗后，两组血清NF-κB p-p65、NF-κB p65、NF-κB p-IκBα、NF-κB IκBα表达水平较治疗前均显著降低（P＜0.05），且治疗后两组比较，试验组NF-κB p-p65、NF-κB p65、NF-κB p-IκBα、NF-κB IκBα表达水平明显低于对照组（P＜0.05）。结论 急性缺血性脑卒中患者应用阿替普酶静脉溶栓24 h后联合阿加曲班抗凝治疗，疗效显著，并发症少，阿加曲班通过对NF-κBp65信号通路的调控，可控地影响患者的凝血功能，改善患者的神经功能以及认知功能，减少卒中后抑郁的发生。

Objective Based on nuclear transcription factors- κB (NF- κB) p65 signaling pathway to explore the efficacy of argatroban combined with alteplase in treatment of acute ischemic stroke and its impact on depression related indicators. Methods A total of 164 patients with acute ischemic stroke without thrombolytic contraindication treated in Xingtai Third Hospital from November 2019 to June 2020 were prospectively selected as the research objects. The patients were randomly divided into control group and experimental group, with 82 cases in each group. Patients in both groups were given intravenous thrombolysis with ateplase, and Clopidogrel Bisulfate was given 24 hours after thrombolysis. Patients in the experimental group were given intravenous infusion of Argatroban Injection 24 hours after thrombolysis on the basis of the control group, and the treatment lasted for four weeks. The levels of activated partial thromboplastin time (APTT) were measured before treatment, immediately after the completion of thrombolytic therapy with ateplase for injection, three hours after the end of thrombolytic therapy, and 48 hours after the end of thrombolytic therapy. The National Institutes of Health stroke scale (NIHSS), Hamilton depression scale (HAMD), mini mental state examination scale (MMSE) and activity of daily living scale (ADL) were used to evaluate the efficacy of two groups. Serum mRNA expression of NF-κB p-p65 and p65, p-IκBα and IκBα were detected by real-time fluorescent quantitative PCR (qRTPCR) before and after treatment. During and after treatment, cerebral hemorrhage, decreased hemoglobin (< 100 g·L^-1), prolonged APTT (> 53 s) and other complications were observed in two groups. Results Before treatment, there was no significant difference in APTT between two groups (P > 0.05). Compared with before treatment, APTT was significantly prolonged in both groups immediately after the end of thrombolytic therapy and three hours after the end of thrombolytic therapy (P < 0.05). Compared with that before treatment, APTT in experimental group basically returned to normal 48 hours after thrombolytic treatment, but it was still significantly prolonged in the control group (P < 0.05). Compared with the control group, the total effective rate of the experimental group was higher (P < 0.05). Compared with the control group, the number of cases of decreased hemoglobin and prolonged APTT in experimental group was slightly lower than that in control group after treatment, but the difference was not statistically significant (P > 0.05). Before treatment, there was no significant difference in NIHSS, HAMD, MMSE and ADL scores between two groups (P > 0.05). After one and four weeks of treatment, NIHSS and HAMD score in control group and experimental group decreased significantly (P < 0.05), and NIHSS and HAMD score in experimental group were lower than those in control group (P < 0.05), while MMSE and ADL score increased significantly (P < 0.05), and MMSE and ADL score in experimental group were higher than those in control group (P < 0.05). After treatment, The expression level of serum NF-κB p-p65, NF-κB p65, NF-κB p-IκBα, NF-κB IκBα of two groups was significantly lower than that before treatment (P < 0.05), and after treatment, the expression level of NF- κB p-p65, NF-κB p65, NF-κB p-IκBα, NF-κB IκBα in experimental group was significantly lower than that in the control group (P < 0.05). Conclusion 24 hours after intravenous thrombolysis with ateplase combined with argatroban anticoagulation in patients with acute ischemic stroke, the curative effect is significant and the complications are less. Argatroban can controllably affect the coagulation function of patients, improve the neurological function and cognitive function of patients, and reduce the occurrence of post-stroke depression by regulating on NF-κB p65 signaling pathway.

R971