丁苯酞对时间窗3~4.5 h急性脑梗死rt-PA静脉溶栓后出血性转化的影响

目的:观察丁苯酞对时间窗3~4.5 h急性脑梗死(ACI)重组组织型纤溶酶原激活物(rt-PA)静脉溶栓后出血性转化(HT)的影响。方法:164例发病3~4.5 h ACI患者随机分为对照组(82例)和观察组(82例)。对照组于影像检查确诊后即刻给予rt-PA静脉溶栓及常规治疗,观察组在对照组的基础上加用丁苯酞氯化钠注射液25 mg/100 mL,于影像检查确诊后即刻静脉滴注,bid。2组均连续治疗14 d。于治疗前和治疗14 d后分别检测2组患者的炎症反应指标[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)]、氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)]和血管内皮功能指标[一氧化氮(NO)、内皮素-1(ET-1)],HT相关指标[基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)、神经元特异性烯醇化酶(NSE)及血浆细胞纤维连接蛋白(c-Fn)],评定神经功能缺损评分(NIHSS)和日常生活能力Barthel指数量表评分(MBI),监测药物的不良反应。结果:治疗14 d后,观察组的临床疗效优于对照组(Z=-1.977,P=0.048);观察组的总有效率高于对照组(χ^2=4.432,P=0.035);治疗14 d内,观察组患者HT发生率低于对照组(χ^2=4.571,P=0.033);治疗14 d后,2组患者的TNF-α、IL-6、MDA、ET-1、MMP-9、c-FN、NSE水平及NIHSS评分均较治疗前显著降低(均P<0.01),SOD、NO、VEGF水平及MBI评分较治疗前显著升高(均P<0.01),而观察组较对照组改善更显著(P<0.01或P<0.05)。2组不良反应发生率比较差异无显著性(χ^2=0.084,P=0.773)。结论:丁苯酞对时间窗3~4.5 h的ACI患者安全有效,可降低HT发生率,改善预后,抗炎、抑制氧化应激损伤及改善血管内皮功能可能为其作用机制。

Effects of butylphthalide pretreatment on hemorrhagic transformation after intravenous thrombolysis of rt-PA in acute cerebral infarction with time window of 3-4.5 h

OBJECTIVE To observe the effect of butylphthalide on hemorrhagic transformation (HT) after intravenous thrombolysis of recombinant tissue plasminogen activator(rt-PA) in acute cerebral infarction(ACI) within the time window of 3-4.5 h.METHODS 164 patients with ACI at 3-4.5 h onset were randomly divided into control group (82 cases) and observation group (82 cases). The patients of the control group were given rt-PA intravenous thrombolysis and routine treatment immediately after diagnosis by imaging. The patients observation group were added with 25 mg/100 mL butylphthalide and sodium chloride injection based on the control group and intravenously infused twice a day immediately after the diagnosis by imaging examination. Both groups were continuously treated for 14 days. Inflammatory response indicators[tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)], oxidative stress index[malondialdehyde(MDA), superoxide dismutase(SOD)] and endothelial function index[nitric oxide(NO) and endothelin-1(ET-1)], HT related index[matrix metalloproteinases-9(MMP-9) and vascular endothelial growth factor(VEGF), neuron specific enolase(NSE) and plasma cellular fibronectin (c-Fn)].Neurological impairment score(NIHSS) and Barthel index scale score(MBI) of the two groups were measured before and 14 days after treatment. The adverse drug reactions were monitored.RESULTS After 14 days of treatment, the clinical efficacy of the observation group was better than that of the control group (Z=-1.977, P=0.048). The total effective rate of observation group was higher than control group (χ²=4.432, P=0.035); The incidence of HT in the observation group was lower than that in the control group within 14 days of treatment (χ²=4.571, P=0.033). After 14 days of treatment, the levels of TNF-α, Il-6, MDA, ET-1, MMP-9, c-Fn, NSE and NIHSS of two groups were significantly lower than those before treatment (all P < 0.01). SOD, NO, VEGF levels and MBI scores were significantly increased compared with those before treatment(all P < 0.01).The improvement in the observation group was more significant than that in the control group(P < 0.01 or P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups(χ²=0.084, P=0.773). CONCLUSION Butylphthalide is safe and effective for ACI patients within the time window of 3-4.5 h, which can reduce the incidence of HT and improve the prognosis. Anti-inflammatory, inhibition of oxidative stress injury and improvement of vascular endothelial function may be involved in its mechanism.