摘要目的 探讨人尿激肽原酶(human urinary kallidinogenase,HUK)对超过溶栓治疗时间窗的急性缺血性卒中患者脑灌注、炎症标志物水平、神经功能缺损以及短期临床转归的影响.方法 回顾性纳入2016年6月至2018年3月期间在南通大学第二附属医院神经内科接受治疗的超过溶栓治疗时间窗,且在入院后第1天和第14天进行磁共振灌注成像的急性缺血性卒中患者,按是否接受HUK治疗分为HUK和对照组.所有患者在入院后第1天和第14天进行磁共振灌注成像及血清炎症标志物测定.比较两组治疗前后美国国立卫生院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、脑灌注水平及血清炎症标志物水平.在入院后14d时根据改良Rankin量表(modified Rankin Scale,mRS)评分进行转归判定,0～2分定义为转归良好,＞2分定义为转归不良.采用多变量logistic回归分析确定转归的独立影响因素.结果 共纳入62例超过溶栓治疗时间窗的急性缺血性卒中患者,其中HUK组37例,对照组25例.除基线NIHSS评分差异有统计学意义(P =0.049)外,HUK组人口统计学和其他基线资料与对照组差异均无统计学意义.HUK组治疗后NIHSS评分降幅较非HUK组更为显著(P＜0.01).HUK组血清高敏C反应蛋白水平在治疗后显著下降(P＜0.01),血浆脂蛋白相关磷脂酶A2也出现下降的趋势.在灌注成像参数方面,HUK组治疗后相对脑血流量显著升高,相对平均通过时间和相对达峰时间均显著下降,上述增幅和降幅与对照组相比差异均有统计学意义(P均＜0.05).入院14 d时mRS评分显示,51例转归良好,11例转归不良.多变量logistic 回归分析显示,基线NIHSS评分[优势比(odds ratio,OR)2.545,95％可信区间(confidence interval,CI)1.124～5.541;P=0.024]、心房颤动(OR 5.712,95％ CI 1.737 ～24.685;P=0.039)以及心源性栓塞(OR 4.485,95％ CI1.148 ～ 18.262;P=0.040)是转归不良的独立危险因素,而是否应用HUK与转归无显著相关性,可能与随访时间较短有关.结论 对于超过溶栓治疗时间窗的急性缺血性卒中患者,HUK可改善脑灌注,减轻炎症反应,改善患者神经功能缺损,但并不能改善神经功能转归.

abstractsObjective To investigate the effects of human urinary kallidinogenase (HUK) on cerebral perfusion,inflammatory marker level,neurological deficits,and short-term clinical outcomes in patients with acute ischemic stroke who exceeded the time window of thrombolytic therapy.Methods Patients with acute ischemic stroke exceeded the time window of thrombolytic therapy and treated in the Department of Neurology,the Second Affiliated Hospital of Nantong University from June 2016 to March 2018,and performed magnetic resonance perfusion imaging on the 1st and 14th d after admission were enrolled retrospectively.Patients were divided into HUK and control groups according to whether they received HUK treatment or not.All patients underwent magnetic resonance perfusion imaging and serum inflammatory markers measurement on the 1st and 14th d after admission.The National Institute of Health Stroke Scale (NIHSS) scores,cerebral perfusion levels,and serum inflammatory marker levels were compared between the 2 groups.On the 14thd after admission,the outcome was determined according to the modifiel Rankin Scale (mRS) scores.0-2 was defined as good outcome and ＞2 was defined as poor outcome.Multivariate logistic regression analysis was used to determine the independent influencing factors of outcome.Results A total of 62 patients with acute ischemic stroke exceeded the time window of thrombolytic therapy were enrolled,including 37 patients in the HUK group and 25 in the control group.There were no significant differences in the demographic and other baseline data between the HUK group and the control group,except for baseline NIHSS score (P =0.049).The reduction of NIHSS score after treatment in the HUK group was more significant than that in the control group (P ＜0.01).Serum high-sensitivity C-reactive protein level in the HUK group decreased significantly after treatment (P ＜ 0.01),and plasma lipoprotein-associated phospholipase A2 also showed a downward trend.In terms of perfusion imaging parameters,the relative cerebral blood flow was significantly increased after treatment in the HUK group,and the relative mean transit time and relative peak time were significantly decreased.The above increase and decrease were statistically significant compared with the control group (all P＜0.05).On the 14th d after admission,the mRS score showed that 51 patients had a good outcome and 11 had a poor outcome.Multivariate logistic regression analysis showed baseline NIHSS scores (odd ratio [OR] 2.545,95％ confilence interval [CI]1.124-5.541;P=0.024),atrial fibrillation (OR 5.712,95％ CI 1.737-24.685;P=0.039),and cardiogenic embolism (OR 4.485,95％ CI 1.148-18.262;P =0.040) were the independent risk factors for poor outcomes,and whether using HUK was not significantly associated with the outcomes.Conclusion For patients with acute ischemic stroke that exceeds the time window for thrombolysis,HUK improves cerebral perfusion,reduces inflammation,and improves neurological deficits in patients,but does not improve short-term neurological outcomes.