目的 基于核轉(zhuǎn)錄因子-κB （NF-κB） p65信號(hào)通路探討阿加曲班聯(lián)合阿替普酶對(duì)急性缺血性腦卒中的療效及對(duì)患者抑郁相關(guān)指標(biāo)的影響。方法 前瞻性選取邢臺(tái)市第三醫(yī)院2019年11月—2020年6月收治的164例發(fā)病4.5 h之內(nèi)的無(wú)溶栓禁忌的急性缺血性腦卒中患者為研究對(duì)象，患者隨機(jī)分為對(duì)照組和試驗(yàn)組，每組82例。兩組患者均給予阿替普酶靜脈溶栓治療，溶栓24 h后均給予硫酸氫氯吡格雷，試驗(yàn)組患者在對(duì)照組基礎(chǔ)上于溶栓24 h后給予阿加曲班靜脈滴注治療，連續(xù)治療4周。分別于治療前、注射用阿替普酶溶栓治療完成即刻、溶栓治療結(jié)束3 h、溶栓治療結(jié)束48 h測(cè)定兩組患者的活化部分凝血活酶時(shí)間（APTT）水平。采用美國(guó)國(guó)立衛(wèi)生研究院卒中量表（NIHSS）、漢密爾頓抑郁量表（HAMD）、簡(jiǎn)易智力狀態(tài)檢查量表（MMSE）、日常生活能力量表（ADL）對(duì)兩組患者進(jìn)行療效評(píng)價(jià)。分別于治療前及治療后采用實(shí)時(shí)熒光定量PCR（qRT-PCR）檢測(cè)兩組患者血清NF-κB p-p65與p65、p-IκBα與IκBα的mRNA表達(dá)。治療期間及治療后，觀察兩組患者腦出血、血紅蛋白下降（＜100 g·L^-1）、APTT延長(zhǎng)（＞53 s）等并發(fā)癥發(fā)生情況。結(jié)果 治療前，兩組患者APTT比較，差異不顯著（P＞0.05）；與治療前比較，溶栓治療結(jié)束即刻和溶栓治療結(jié)束3 h，兩組患者APTT均顯著延長(zhǎng)（P＜0.05）；與治療前比較，溶栓治療結(jié)束48 h試驗(yàn)組APTT基本恢復(fù)正常，但對(duì)照組仍顯著延長(zhǎng)（P＜0.05）；相比于對(duì)照組，試驗(yàn)組的總有效率更高（P＜0.05）；與對(duì)照組比較，治療后，試驗(yàn)組血紅蛋白下降以及APTT延長(zhǎng)發(fā)生例數(shù)略低于對(duì)照組，但差異無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.05）；治療前，兩組患者NIHSS、HAMD、MMSE、ADL評(píng)分比較，差異均無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.05）；治療1周以及4周后，對(duì)照組和試驗(yàn)組NIHSS、HAMD評(píng)分顯著降低（P＜0.05），且試驗(yàn)組患者的NIHSS、HAMD評(píng)分低于對(duì)照組（P＜0.05），同時(shí)MMSE、ADL評(píng)分顯著升高（P＜0.05），且試驗(yàn)組患者的MMSE、ADL評(píng)分高于對(duì)照組（P＜0.05）；治療后，兩組血清NF-κB p-p65、NF-κB p65、NF-κB p-IκBα、NF-κB IκBα表達(dá)水平較治療前均顯著降低（P＜0.05），且治療后兩組比較，試驗(yàn)組NF-κB p-p65、NF-κB p65、NF-κB p-IκBα、NF-κB IκBα表達(dá)水平明顯低于對(duì)照組（P＜0.05）。結(jié)論 急性缺血性腦卒中患者應(yīng)用阿替普酶靜脈溶栓24 h后聯(lián)合阿加曲班抗凝治療，療效顯著，并發(fā)癥少，阿加曲班通過(guò)對(duì)NF-κBp65信號(hào)通路的調(diào)控，可控地影響患者的凝血功能，改善患者的神經(jīng)功能以及認(rèn)知功能，減少卒中后抑郁的發(fā)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.

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