人尿激肽原酶对大脑中动脉中重度狭窄所致急性缺血性卒中患者脑血管储备功能的影响

doi:10.3969/j.issn.1673-5765.2023.11.009

摘要/Abstract

摘要： 目的探讨人尿激肽原酶对大脑中动脉中重度狭窄所致急性缺血性卒中患者脑血管储备功能的影响。
方法前瞻性纳入2020年1月—2021年12月在郑州人民医院神经内科住院的大脑中动脉中重度狭窄所致急性缺血性卒中患者。采用随机数字表法，将入组患者分为对照组和人尿激肽原酶组。对照组进行常规治疗；人尿激肽原酶组在对照组治疗基础上，给予静脉滴注人尿激肽原酶，每次0.15 PNA单位，溶于100 mL 0.9%氯化钠注射液，静脉滴注时间不少于50 min，持续10～14 d。治疗前及治疗后3个月，采用TCD检测大脑中动脉脑血管储备功能（cerebrovascular reserve，CVR）、屏气指数（breath-holding index，BHI），临床疗效评价采用NIHSS评分和mRS评分。
结果共入组120例患者，平均年龄（63.0±6.5）岁，对照组和人尿激肽原酶组各60例。治疗前，两组的CVR和BHI差异无统计学意义；治疗后，与对照组相比，人尿激肽原酶组的CVR[（37.2%±4.1%）vs.（23.1%±3.2%），P＜0.001]和BHI[（1.64±0.40）vs.（1.14±0.34），P＜0.001]均显著增高。治疗前两组的NIHSS评分、mRS评分0～2分患者的比例差异无统计学意义；治疗3个月后，人尿激肽原酶组NIHSS评分低于对照组[4（3～5）分 vs. 5（3～6）分，P=0.022]，mRS评分0～2分患者的比例高于对照组[55.0% vs. 35.0%，P=0.028]。
结论人尿激肽原酶注射液可改善大脑中动脉中重度狭窄所致急性缺血性卒中患者的CVR，并改善患者3个月的预后。

文章导读： 本研究在单中心、小样本的随机对照试验中初步验证了人尿激肽原酶可有效改善急性缺血性卒中患者的脑血流储备，有利于患者神经功能的恢复。

关键词: 人尿激肽原酶; 缺血性卒中; 脑血管储备; 预后

Abstract: Objective To investigate the effect of human urinary kininogenase on cerebrovascular reserve in patients with acute ischemic stroke caused by moderate to severe stenosis of the middle cerebral artery.
Methods Patients with acute ischemic stroke caused by moderate to severe stenosis of the middle cerebral artery who were hospitalized in the Department of Neurology, People's Hospital of Zhengzhou from January 2020 to December 2021 were prospectively enrolled. The enrolled patients were divided into control group and human urinary kininogenase group by random number table method. The control group received conventional treatment. On the basis of the treatment of the control group, the human urinary kininogenase group was given intravenous infusion of human urinary kininogenase with 0.15 PNA units each time, dissolved in 100 mL of 0.9% sodium chloride injection, and the intravenous infusion time was not less than 50 min, lasting 10-14 days. Before treatment and 3 months after treatment, TCD was used to evaluate the cerebrovascular reserve (CVR) and breath-holding index (BHI) of the middle cerebral artery, respectively, and the clinical efficacy evaluation was carried out using NIHSS score and mRS score.
Results 120 patients with an average age of (63.0±6.5) years were enrolled, including 60 cases in the control group and 60 cases in the human urinary kininogenase group. Before treatment, there were no statistically significant differences in CVR and BHI between the two groups. After treatment, compared with the control group, the CVR [(37.2%±4.1%) vs. (23.1%±3.2%), P<0.001] and BHI [(1.64±0.40) vs. (1.14±0.34), P<0.001] in the human urinary kininogenase group were significantly increased. There was no significant difference in the proportion of patients with NIHSS score and mRS score of 0-2 between the two groups before treatment. Three months after treatment, the NIHSS score of the human urinary kininogenase group was lower than that of the control group [4 (3-5) points vs. 5 (3-6) points, P=0.022]. The proportion of mRS score of 0-2 points of the human urinary kininogenase group was higher than that of the control group [55% vs. 35%, P=0.028].
Conclusions Human urinary kininogenase injection can improve the CVR of patients with acute ischemic stroke caused by moderate to severe stenosis of the middle cerebral artery, and can improve the prognosis of patients at 3 months.

Key words: Human urinary kininogenase; Ischemic stroke; Cerebrovascular reserve; Prognosis

付胜奇, 石宝洋, 李浩然, 朱利利, 胡胜洁, 张津, 禹萌. 人尿激肽原酶对大脑中动脉中重度狭窄所致急性缺血性卒中患者脑血管储备功能的影响[J]. 中国卒中杂志, 2023, 18(11): 1277-1281.

FU Shengqi, SHI Baoyang, LI Haoran, ZHU Lili, HU Shengjie, ZHANG Jin, YU Meng. The Effect of Human Urinary Kininogenase on Cerebrovascular Reserve in Patients with Acute Ischemic Stroke due to Moderate to Severe Stenosis of the Middle Cerebral Artery [J]. Chinese Journal of Stroke, 2023, 18(11): 1277-1281.

参考文献

[1] 中华医学会神经病学分会，中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南2018[J]. 中华神经科杂志，2018，51（9）：666-682.
Chinese Society of Neurology，Chinese Stroke Society. Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018[J]. Chin J Neurol，2018，51（9）：666-682.
[2] RAO V L，PROLO L M，SANTORO J D，et al. Acetazolamide-challenged arterial spin labeling detects augmented cerebrovascular reserve after surgery for moyamoya[J]. Stroke，2022，53（4）：1354-1362.
[3] 吉林省医学会神经病学分会，吉林省卒中学会. 动态脑血流自动调节功能评估在神经系统疾病中的临床应用专家共识（2021）[J/OL]. 中华脑血管病杂志（电子版），2021，15（3）：140-152[2023-01-10].
https://zhnxgbzz.cma-cmc.com.cn/CN/10.11817/j.issn.1673-9248.2021.03.003.
Neurology Branch of Jilin Province Medical Association，Jilin Province Stroke Association. Expert consensus on the clinical application of dynamic cerebral autoregulation assessment in neurological diseases（2021）[J/OL]. Chin J Cerebrovasc Dis（Electtronic Edition），2021，15（3）：140-152[2023-01-10]. https://zhnxgbzz.cma-cmc.com.cn/CN/10.11817/j.issn.1673-9248.2021.03.003.
[4] YANG D X，LI Y，YU D，et al. Human urinary kallidinogenase combined with edaravone in treating acute ischemic stroke patients：a meta-analysis[J/OL]. Brain Behav，2021，11（12）：e2431[2023-01-01]. https://doi.org/10.1002/brb3.2431.
[5] NI J，YAO M，WANG L H，et al. Human urinary kallidinogenase in acute ischemic stroke：a single-arm，multicenter，phase IV study（RESK study）[J]. CNS Neurosci Ther，2021，27（12）：1493-1503.
[6] LINDBOHM J V，KAPRIO J，JOUSILAHTI P，et al. Sex，smoking，and risk for subarachnoid hemorrhage[J]. Stroke，2016，47（8）：1975-1981.
[7] CHIMOWITZ M I，LYNN M J，HOWLETT-SMITH H，et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis[J]. N Engl J Med，2005，352（13）：1305-1316.
[8] HAN D，CHEN X，LI D m，et al. Human urinary kallidinogenase decreases recurrence risk and promotes good recovery[J/OL]. Brain Behav，2018，8（8）：e1033[2023-01-05]. https://doi.org/10.1002/brb3.1033.
[9] DONG Y，QU J Z，ZHANG Z J，et al. Human urinary kallidinogenase in treating acute ischemic stroke patients：analyses of pooled data from a randomized double-blind placebo-controlled phase IIb and phase III clinical trial[J]. Neurol Res，2020，42（4）：286-290.
[10] WEI Z Y，LYU Y，YANG X L，et al. Therapeutic values of human urinary kallidinogenase on cerebrovascular diseases[J/OL]. Front Neurol，2018，9：403[2023-01-05]. https://doi.org/10.3389/fneur.2018.00403.
[11] 龚浠平，司丽萍，白亚秋，等. 注射用尤瑞克林对急性缺血性卒中患者脑血流储备能力的影响[J]. 中国卒中杂志，2009，4（7）：581-584.
GONG X P，SI L P，BAI Y Q，et al. Effect of urinary kallidinogenase injection on cerebrovascular reserve capacity in patients with ischemic stroke[J]. Chin J Stroke，2009，4（7）：581-584.
[12] RABILLER G，HE J W，NISHIJIMA Y，et al. Perturbation of brain oscillations after ischemic stroke：a potential biomarker for post-stroke function and therapy[J]. Int J Mol Sci，2015，16（10）：25605-25640.

[1]	吴敌, 荆京, 潘岳松, 陈绪珠, 赵性泉. 自发性颈动脉夹层相关缺血性卒中颅内缺血病灶分布特征与受累血管节段的关系研究[J]. 中国卒中杂志, 2023, 18(9): 993-1000.
[2]	程忻, 仲伟逸, 董漪, 李琦, 倪伟, 谷鸿秋, 顾宇翔, 董强, 中国卒中学会中国脑血管病临床管理指南撰写工作委员会. 中国脑血管病临床管理指南（第2版）（节选）——第6章蛛网膜下腔出血临床管理推荐意见[J]. 中国卒中杂志, 2023, 18(9): 1024-1029.
[3]	王丽佳, 时代, 刘慧慧, 曹勇军, 刘春风, 石际俊. 茎突综合征相关颈内动脉夹层致缺血性卒中1例报道[J]. 中国卒中杂志, 2023, 18(9): 1049-1053.
[4]	任晓佳, 刘关杰, 郝汶强. 金纳多治疗烟雾病所致缺血性卒中个案报道[J]. 中国卒中杂志, 2023, 18(9): 1060-1064.
[5]	陆靖, 李传发, 张大启, 陈蓉, 李其富. 急性缺血性卒中血管内治疗后出血转化的研究进展[J]. 中国卒中杂志, 2023, 18(9): 1065-1072.
[6]	周雨萌, 陈丽霞. 急性缺血性卒中机械取栓患者的血压管理研究进展[J]. 中国卒中杂志, 2023, 18(9): 1073-1078.
[7]	李超, 姜英玉, 张心邈, 杨昕, 王春娟, 谷鸿秋, 杜珂瑾, 王拥军, 李子孝. 缺血性卒中后出血转化的影响因素分析[J]. 中国卒中杂志, 2023, 18(9): 1079-1084.
[8]	霍洁, 徐玢, 张初吉, 陈必耀, 冀瑞俊, 袁靖. 血清淀粉酶升高对急性卒中患者短期死亡的预测价值[J]. 中国卒中杂志, 2023, 18(8): 873-878.
[9]	程实, 李静, 郭军平, 胡爱香, 于鑫玮, 韩玮, 梁瑛, 冀瑞俊, 张越巍. 卒中后感染对急性缺血性卒中患者出院结局的影响[J]. 中国卒中杂志, 2023, 18(8): 885-890.
[10]	刘丽萍, 周宏宇, 段婉莹, 霍晓川, 聂曦明, 刘慧慧, 李子孝, 徐蔚海, 李淑娟, 缪中荣, 王拥军, 中国卒中学会中国脑血管病临床管理指南撰写工作委员会. 中国脑血管病临床管理指南（第2版）（节选）——第4章缺血性脑血管病临床管理推荐意见[J]. 中国卒中杂志, 2023, 18(8): 910-933.
[11]	范萍, 岳奎涛, 李爱媛, 赵喆, 谢海, 吴春艳（第一作者）. 影像组学在急性缺血性卒中中的应用进展[J]. 中国卒中杂志, 2023, 18(8): 952-957.
[12]	陈义彤, 武美茹, 苗亚杰, 魏文宇, 李子孝. 定制个体化可视化健康教育在缺血性卒中患者中的应用[J]. 中国卒中杂志, 2023, 18(8): 959-965.
[13]	张磊, 王小雅, 坚雅婷, 高震, 樊洪, 范松华, 王虎清, 孙宏, 张茹, 展淑琴, 张桂莲. 症状性颈动脉漂浮血栓的血管内治疗探索[J]. 中国卒中杂志, 2023, 18(10): 1136-1142.
[14]	谷鸿秋, 杨凯璇, 姜英玉, 杜柯瑾, 饶蓁蓁, 杨昕, 王春娟, 熊云云, 荆京, 李子孝. 缺血性卒中患者卒中复发风险预测模型研究进展及展望 [J]. 中国卒中杂志, 2023, 18(07): 731-739.
[15]	王垚, 秦海强, 王安心, 张晓丽, 左颖婷, 张亚清, 杨波, 于丹丹, 魏娜, 张婧. 卒中患者入院体重指数与3个月预后的关系研究[J]. 中国卒中杂志, 2023, 18(07): 793-798.