rt-PA静脉溶栓与超选择性动脉溶栓治疗急性大脑中动脉脑梗死临床分析

贺新霞

巩义市人民医院神经内科，河南巩义 451200

作者简介：贺新霞，Email：hxx991231@163.com

【摘要】 目的 探讨rt-PA静脉溶栓与超选择性动脉溶栓治疗急性大脑中动脉脑梗死的临床效果。方法 分析巩义市人民医院2015-01—2018-02收治的240例急性大脑中动脉脑梗死患者的临床资料，依据治疗方式分为rt-PA静脉溶栓组210例和超选择性动脉溶栓组30例。观察2组不同时间点NIHSS评分、纤维蛋白原(FIB)、凝血酶原时间(PT)及凝血酶时间(TT)情况，对比2组血管再通率、总有效率。结果 2组溶栓前NIHSS评分、FIB、PT、TT比较，差异均无统计学意义(P＞0.05)，超选择性动脉溶栓组溶栓6 h、3 d、7 d NIHSS评分、PT、TT均低于rt-PA静脉溶栓组，FIB均高于rt-PA静脉溶栓组，超选择性动脉溶栓组血管再通率、总有效率均高于rt-PA静脉溶栓组，差异有统计学意义(P＜0.05)。结论 超选择性动脉溶栓治疗急性大脑中动脉脑梗死，患者神经功能和凝血功能改善，血管再通率、总有效率均较高。

【关键词】 急性大脑中动脉脑梗死；缺血性脑血管病；rt-PA；静脉溶栓；超选择性动脉溶栓；颈内动脉

【中图分类号】  R743.33    【文献标识码】  A    【文章编号】  1673-5110(2018)24-2749-06  DOI：10.12083/SYSJ.2018.24.572

Department of Neurology，Gongyi People's Hospital，Gongyi 451200，China

【Abstract】  Objective  To investigate the clinical effect of rt-PA intravenous thrombolysis and superselective arterial thrombolysis in the treatment of acute middle cerebral artery cerebral infarction.Methods  The clinical data of 240 patients with acute middle cerebral artery cerebral infarction admitted to Gongyi People's Hospital from January 2015 to Februay 2018 were analyzed.According to the treatment，210 patients with rt-PA intravenous thrombolysis and 30 patients with superselective arterial thrombolysis.The NIHSS score，fibrinogen (FIB)，prothrombin time (PT) and thrombin time (TT) were observed at different time points in the two groups.The revascularization rate and total effective rate of the two groups were compared.Results  There were no significant differences in NIHSS scores，FIB，PT and TT between the two groups before thrombolysis (P＞0.05)．The super-selective arterial thrombolysis group was treated with TSH for 6h，3d，7d，NIHSS score，PT，TT was lower than rt-PA intravenous thrombolysis group，FIB was higher than rt-PA intravenous thrombolysis group，and the recanalization rate and total effective rate of superselective arterial thrombolysis group were higher than that of rt-PA intravenous thrombolysis group.The difference was statistically significant (P＜0.05)．Conclusion  Superselective arterial thrombolysis is effective in the treatment of acute middle cerebral artery cerebral infarction.The neurological function and coagulation function are improved，and the recanalization rate and total effective rate are high.

【Key words】  Acute middle cerebral artery cerebral infarction；Ischemic cerebrovascular disease；rt-PA；Intravenous thrombolysis；Superselective arterial thrombolysis；Internal carotid artery

        急性大脑中动脉脑梗死属于颈内动脉系统急性脑梗死的常见类型，主要是因脑组织血容量减少诱发缺血坏死造成的，患者预后相对较差，然而动脉主干闭塞患者的病死率更加高^[1-6]。脑梗死的缺血区域可以分为中心区和周边区，中心区缺血发生的短时间内会诱发神经细胞死亡^[7-12]。溶栓治疗是临床常用的治疗方法，主要包括静脉溶栓和动脉溶栓两种^[13-18]。静脉溶栓操作较简单，临床应用较广泛，但其使用药物量较大。动脉溶栓主要是促进闭塞血管再通，在降低药物应用量的同时提高临床治疗效果，获得更好的脑组织血液循环。本研究通过分析巩义市人民医院2015-01—2018-02收治的240例急性大脑中动脉脑梗死患者的临床资料，拟探讨rt-PA静脉溶栓与超选择性动脉溶栓治疗急性大脑中动脉脑梗死的临床效果。

1．1  临床资料 选取巩义市人民医院2015-01—2018-02收治的240例急性大脑中动脉脑梗死患者，依据治疗方式分组，rt-PA静脉溶栓组210例，男131例，女79例，年龄50～66(55.8±6.8)岁，发病时间1～7(3.9±0.6)h；超选择性动脉溶栓组30例，男19例，女11例，年龄51～65(56.3±6.2)岁，发病时间1～7(3.7±0.5)h。纳入标准：(1)符合《中国急性缺血性脑卒中诊治指南2014》对急性大脑中动脉脑梗死的诊断标准^[7]；(2)年龄30～80岁；(3)发病到溶栓时间＜6 h；(4)参照NIHSS评分标准，评分4～24分。排除标准：(1)溶栓前通过影像学检查发现出血性病灶；(2)发病早期有癫痫发作者；(3)既往有动脉炎、蛛网膜下腔出血及脑出血史者；(4)很难控制的高血压、高血糖；(5)合并严重的心、肾、肝功能障碍，恶性肿瘤和造血功能障碍者；(6)溶栓前有凝血功能障碍、血常规异常者；(7)近1个月有严重的外伤、外科手术和器官活检者；(8)6个月内有胃肠道出血、泌尿系统大出血、消化性溃疡、动静脉畸形、颅内动脉瘤及出血性视网膜病变者。本研究经院道德伦理委员会批准，患者对本次研究知情同意。2组一般资料比较差异无统计学意义(P＞0.05)，具有可比性。

1．2  方法 rt-PA静脉溶栓组：设定rt-PA(德国勃林格殷格翰公司)剂量0.9 mg/kg，静滴总剂量的10%，时间1 min，然后将剩余90%的rt-PA＋100 mL 0.9%氯化钠注射液静滴，时间1 h，溶栓后24 h通过头颅CT对颅内出血情况进行复查，阿司匹林200 mg/d口服。超选择性动脉溶栓组：采用2%利多卡因局部麻醉，然后通过改良Seldinger法经右侧股动脉穿刺，放置5F股动脉鞘，直到颈动脉内。采用5 000 U肝素静脉注射，全身肝素化，采用全脑数字减影血管造影(DSA)对闭塞血管进行确认，放置溶栓微导管，一直到达血栓处，首次采用UK 20万IU，通过1万U·min^-1的速度持续性泵入，结束观察10～15 min进行复查DSA，如果血管恢复后再通，停止溶栓治疗。如果未恢复再通，再次以2.5万U·min^-1的速度逐步泵入，UK总量30万IU，直到恢复再通，总用量＜100万IU。溶栓结束后，对肝素进行中和，溶栓结束后4 h，将动脉鞘管拔除，压迫30 min止血，再给予绷带加压，右侧下肢给予制动处理，手术后8 d内保持卧床休息。2组溶栓24 h内不进行抗凝治疗和抗血小板治疗，24 h后给予抗血小板治疗、神经保护治疗和改善微循环治疗。

1．3.1  NIHSS评分情况：观察溶栓前、溶栓 6 h、3 d、7 d 的NIHSS评分。NIHSS评分标准^[19]：主要观察患者的意识水平、凝视、视野、面瘫、上下肢运动、肢体共济失调、感觉、语言、构音障碍、忽视，总分0～42分，分数越高提示患者的神经功能缺损越严重。

1．3.2  凝血指标情况：观察2组溶栓前、溶栓6 h、3 d、7 d时的凝血指标情况，主要包括纤维蛋白原(FIB)、凝血酶原时间(PT)及凝血酶时间(TT)。

1．3.3  血管再通率情况：根据DSA观察血管再通情况，分为三级^[20-21]。完全再通：血管闭塞，局部周围无责任血管，通过血管显影显示清楚；部分再通：血管闭塞，血管远端部分显影，血管显影相对浅淡或显示不清楚；未再通：闭塞的血管远端完全未显影。再通率＝(完全再通＋部分再通)/总例数×100%。

1．3.4  临床疗效：参照《中国急性缺血性脑卒中诊治指南2014》进行效果评价^[7]，临床治愈：患者临床症状、体征均消失，NIHSS评分降低＞90%，肢体病残程度评价为0；显效：患者临床症状获得明显改善，NIHSS评分降低46%～90%，肢体病残程度评价为1～3 级；有效：患者临床症状、体征稍有改善，NIHSS评分降低18%～45%；无效：临床症状、体征均没有明显改善，甚至有恶化倾向，NIHSS评分降低＜18%，甚至有升高趋势。总有效率＝(临床治愈＋显效＋有效)/总例数×100%。

1．4  统计学分析 采用统计学软件SPSS 19.0处理数据，计量资料采用均数±标准差表示，采取t检验，计数资料通过百分率表示，采取卡方检验，P＜0.05为差异有统计学意义。

2．1  2组不同时间点NIHSS评分情况  2组溶栓前NIHSS评分比较，差异无统计学意义(P＞0.05)，超选择性动脉溶栓组溶栓6 h、3 d、7 d NIHSS评分均低于rt-PA静脉溶栓组，差异有统计学意义(P＜0.05)。见表1。

2．2  2组溶栓前、溶栓6 h、3 d、7 d时凝血指标情况  2组溶栓前FIB、PT、TT比较，差异均无统计学意义(P＞0.05)，超选择性动脉溶栓组溶栓6 h、3 d、7 d FIB均高于rt-PA静脉溶栓组，PT、TT均低于rt-PA静脉溶栓组，差异有统计学意义(P＜0.05)。见表2。

2．3  2组血管再通情况 超选择性动脉溶栓组再通率高于rt-PA静脉溶栓组，差异有统计学意义(P＜0.05)。见表3。

2．4  2组临床疗效比较 超选择性动脉溶栓组总有效率高于rt-PA静脉溶栓组，差异有统计学意义(P＜0.05)。见表4。

表1  2组不同时间点NIHSS评分比较  (x±s，分)

Table 1 Comparison of NIHSS scores at different time points in 2 groups  (x±s，scores) 

表2  2组溶栓前、溶栓6 h、3 d、7 d时凝血指标比较  (x±s)

Table 2 Comparison of coagulation indicators before thrombolysis，6h，3d，7d after thrombolysis of 2 groups  (x±s)

组别	n	溶栓前	溶栓6 h	溶栓3 d	溶栓7 d
rt-PA静脉溶栓组	210
FIB		3.8±0.6	1.5±0.5	2.6±0.4	3.7±0.5
PT		11.6±1.2	14.8±1.6	13.3±1.5	12.4±0.9
TT		15.2±1.6	30.2±7.5	20.2±4.1	17.7±1.1
超选择性动脉溶栓组	30
FIB		3.7±0.5	3.1±0.4#	3.4±0.5#	3.9±0.4#
PT		11.7±1.3	12.6±1.3#	11.7±1.0#	11.2±0.8#
TT		15.4±1.5	20.6±4.4#	16.4±2.8#	15.2±1.3#

              注：与rt-PA静脉溶栓组比较，^#P＜0.05 

表3  2组血管再通情况比较  [n(%)]

Table 3 Comparison of blood vessel recanalization of two groups  [n(%)]

组别	n	完全再通	部分再通	部分再通	再通率/%
rt-PA静脉溶栓组	210	80(38.1)	75(35.7)	55(26.2)	73.8
超选择性动脉溶栓组	30	23(76.7)	4(13.3)	3(10)	90
χ2值					19.63
P值					＜0.05

表4  2组临床疗效比较  [n(%)]

Table 4 Comparison of clinical efficacy of 2 groups  [n(%)]

组别	n	临床治愈	显效	有效	无效	总有效率/%
rt-PA静脉溶栓组	210	65(31.0)	60(28.6)	30(14.3)	55(26.2)	73.8
超选择性动脉溶栓组	30	18(60)	6(20)	3(10)	3(10)	90
χ2值						19.63
P值						＜0.05

        急性大脑中动脉脑梗死属于急性脑梗死较为严重的类型，是临床治疗工作的重点和难点^[22-26]。急性大脑中动脉脑梗死时间窗较短，给予及时的针对性治疗，对于提高患者预后具有重要的意义^[27-35]。目前急性大脑中动脉脑梗死多采用溶栓治疗，通过溶解血栓，促进缺血组织血液灌注，提高临床治疗效果。溶栓方法分为静脉溶栓和动脉溶栓。

        本研究中对照组采用rt-PA静脉溶栓，静脉溶栓主要通过静滴溶栓药物，促使血栓溶解和血管再通，操作简便易行，通过静滴药物造成的继发性创伤较小^[36-38]，但用药量较大，并发症相对较多。观察组采用超选择性动脉溶栓治疗，动脉溶栓促进血栓和药物接触，降低了药物的应用量。超选择性动脉溶栓是一种介入方法，通过微导管将溶栓药物直接作用在梗死的病灶^[39-40]，可以更好地改善患者的神经功能，由于超选择性动脉溶栓用药剂量低于rt-PA静脉溶栓，对于凝血功能的影响相对较小^[41-42]；另外，超选择性动脉溶栓在局部病灶的药物浓度更高^[42]，因而可以提高血管再通效率和临床疗效。

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(收稿2018-11-10 修回2018-12-06)

本文责编：关慧

本文引用信息：贺新霞．rt-PA静脉溶栓与超选择性动脉溶栓治疗急性大脑中动脉脑梗死临床分析[J]．中国实用神经疾病杂志，2018，21(24)：2749-2754.DOI：10.12083/SYSJ.2018.24.572