目的 探讨阿加曲班联合尤瑞克林治疗急性缺血性脑卒中的临床效果及对神经损伤标志物的影响。方法 前瞻性选择2018年10月—2021年1月邢台市第三医院收治的202例急性缺血性脑卒中患者，随机将患者分成对照组和试验组，每组各101例，对照组患者在基础治疗的同时加用注射用尤瑞克林，应用100 mL 0.9%氯化钠注射液稀释0.15 PNA注射用尤瑞克林，静脉滴注，每日1次，疗程为30 d。试验组患者在对照组的基础上应用阿加曲班注射液，治疗前2 d，使用60 mg阿加曲班，稀释液为1 500 mL 0.9%氯化钠注射液，静脉滴注24 h；从第3天开始，阿加曲班剂量更改为10 mg，100 mL 0.9%氯化钠注射液稀释，静脉滴注持续3 h，每日1次，阿加曲班和尤瑞克林均持续用药30 d。比较两组患者神经功能、日常生活能力、生活质量、临床疗效、炎性因子、血液流变学、神经损伤标志物、安全性及预后等指标。结果 治疗后，两组反映患者神经功能的美国国立卫生研究院卒中量表（NIHSS）评分较治疗前均显著降低（P＜0.05），反映患者日常生活能力的改良版Barthel指数（MBI）评分和反映患者生活质量的世界卫生组织生存质量测定量表（WHOQOL-100）评分均显著升高（P＜0.05）。治疗后，试验组NIHSS评分明显低于对照组（P＜0.01），且MBI评分和WHOQOL-100评分明显高于对照组（P＜0.01）。试验组患者临床总有效率（88.12%）明显高于对照组（68.32%），经χ²检验，差异具有统计学意义（P＜0.01）。治疗后，试验组患者血清炎性因子C反应蛋白（CRP）、白细胞介素-2（IL-2）水平及血小板聚集率、纤维蛋白原、红细胞比容、血浆黏度等血液流变学指标均显著低于对照组（P＜0.01），试验组血清谷氨酸、S100β蛋白、神经元特异性烯醇化酶等神经损伤标志物水平均显著低于对照组（P＜0.01）。试验组患者不良反应发生率与对照组比较，差异不显著（P＞0.05）。试验组患者预后良好率（60.00%）显著高于对照组（41.41%），差异具有统计学意义（P＜0.01）。结论 阿加曲班联合尤瑞克林治疗急性缺血性脑卒中，可有效改善患者神经功能，增强日常生活能力，提高生活质量，消除炎症反应，改善血液流变学指标，降低神经损伤标志物的水平，临床应用有效。

Objective To investigate the clinical effect of argatroban combined with urinary kallindinogenase in treatment of acute ischemic stroke and its effect on nerve injury markers. Methods A total of 202 patients with acute ischemic stroke treated in Xingtai Third Hospital from October 2018 to January 2021 were prospectively selected. The patients were randomly divided into control group and experimental group, with 101 patients in each group. The patients in the control group were treated with Urinary Kallindinogenase for Injection while basic treatment, diluted with 100 mL of 0.9% Sodium Chloride Injection for 0.15 PNA, intravenous drip once a day, the course of treatment was 30 d. The patients in the experimental group were treated with Argatroban Injection on the basis of the control group. Two days before treatment, 60 mg Argatroban Injection was used, and the diluent was 1 500 mL of 0.9% Sodium Chloride Injection, intravenous drip for 24 h, from the third day, the dose of Argatroban Injection was changed to 10 mg, 100 mL of 0.9% Sodium Chloride Injection was diluted, intravenous drip lasted for three hours, once a day, and argatroban and urinary kallindinogenase were used for 30 d. The neurological function, activities of daily living, quality of life, clinical efficacy, inflammatory factors, hemorheology, markers of nerve injury, safety and prognosis were compared between the two groups. Results After treatment, the NIHSS score reflecting the neurological function of the patients in the two groups was significantly lower than that before treatment (P < 0.05), and the modified Barthel Index (MBI) score reflecting the ability of daily living and the WHO quality of life scale (WHOQOL-100) score reflecting the quality of life of the patients were significantly higher (P < 0.05). After treatment, the NIHSS score in the experimental group was significantly lower than that in the control group (P < 0.01), and MBI score and the WHOQOL-100 score were significantly higher than those in the control group (P < 0.01). The total clinical effective rate of the experimental group (88.12%) was significantly higher than that of the control group (68.32%), χ² test, the difference was statistically significant (P < 0.01). After treatment, the levels of serum inflammatory factor C-reactive protein (CRP), interleukin-2 (IL-2) and hemorheological indexes such as platelet aggregation rate, fibrinogen, hematocrit and plasma viscosity in the experimental group were significantly lower than those in the control group (P < 0.01). Markers of nerve injury such as glutamic acid, S100β protein, and neuron specific enolaseand were significantly lower than those in the control group (P < 0.01). The total incidence of adverse reactions in the two groups was not statistically significant (P > 0.05). The rate of good prognosis in the experimental group (60.00%) was significantly higher than that in the control group (41.41%). The difference was statistically significant (P < 0.01). Conclusion Argatroban combined with urinary kallindinogenase in treatment of acute ischemic stroke can effectively improve the neurological function, enhance the ability of daily living, improve the quality of life, eliminate inflammatory reaction, improve hemorheological indexes and reduce the level of nerve injury markers.The clinical application is effective.

R971

邢台市重点研发计划项目（2020ZC185）