摘要：

目的 探讨三七总皂苷对急性缺血性卒中患者重组组织型纤溶酶原激活物（rt-PA）静脉溶栓疗效和出血性转化的影响。方法 共200 例急性（发病至入院时间< 4.50 h）缺血性卒中患者采用随机数字表法随机分为常规rt-PA 静脉溶栓组（对照组，100 例）和rt-PA 静脉溶栓联合三七总皂苷治疗组（治疗组，100 例），分别于治疗前、静脉溶栓后24 h 和14 d 检测缺血-再灌注损伤指标［丙二醛（MDA）、超氧化物歧化酶（SOD）］、出血性转化指标［基质金属蛋白酶-9（MMP-9）、纤维连接蛋白（FN）］和神经功能指标［美国国立卫生研究院卒中量表（NIHSS）、Barthel 指数（BI）］，观察静脉溶栓后14 d 药物不良反应和出血性转化发生率，评价静脉溶栓后12 个月预后（病死率和BI评分）。结果 治疗组患者血清SOD（P = 0.000）和BI 评分（P = 0.000）高于，血清MDA（P = 0.001）和MMP-9（P = 0.001）、血浆FN（P = 0.000）和NIHSS 评分（P = 0.006）低于对照组。rt-PA 静脉溶栓联合三七总皂苷治疗后24 h，血清MDA（P = 0.000）和MMP-9（P = 0.000）、BI 评分（P = 0.000）升高，NIHSS 评分降低（P = 0.000）；治疗后14 d，血清MDA（P = 0.000）和MMP-9（P = 0.000）反而降低，血清SOD（P = 0.000）和BI 评分（P = 0.000）持续升高，血浆FN（P = 0.000）和NIHSS 评分（P = 0.000）持续降低。静脉溶栓后14 d，治疗组患者出血性转化发生率低于对照组［9 例（9%）对19 例（19%）；χ² = 4.153，P = 0.042）］，药物不良反应发生率组间差异无统计学意义［14 例（14%）对11 例（11%）；χ² = 0.411，P = 0.521］。静脉溶栓后12 个月，两组病死率差异无统计学意义［5 例（5%）对1 例（1%）；χ² = 1.546，P = 0.241］，而治疗组生存患者BI 评分高于对照组（88.51 ± 11.49 对84.47 ± 9.83；t = 2.451，P = 0.015）。结论 三七总皂苷可以减轻急性缺血性卒中患者rt-PA 静脉溶栓后缺血-再灌注损伤，降低出血性转化发生率，改善患者预后，且安全性良好。

关键词: 卒中, 脑缺血, 三七皂甙, 组织型纤溶酶原激活物, 脑出血

Abstract:

Objective  To study the effect of panax notoginseng saponins (PNS) on the efficacy and hemorrhagic transformation (HT) of recombinant tissue-type plasminogen activator (rt-PA) intravenous thrombolysis in patients with acute ischemic stroke.  Methods  A total of 200 patients with early acute ischemic stroke (the length of time between attack and hospital admission < 4.50 h) were divided into 2 groups according to random number table method: treatment group (N = 100) and control group (N = 100). The control group was treated with routine rt-PA intravenous thrombolysis treatment, and the treatment group was treated with rt-PA intravenous thrombolysis plus PNS injection. The ischemia-reperfusion injury index [malondialdehyde (MDA) and superoxide dismutase (SOD)], hemorrhagic transformation prediction index [matrix metalloproteinase-9 (MMP-9) and fibronectin (FN)] and nerve function index [National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI)] were measured and compared before treatment, 24 h after thrombolysis and 14 d after thrombolysis. Adverse drug reactions and hemorrhagic transformation rate were observed 14 d after thrombolysis, and the prognosis (mortality and BI) was evaluated 12 months after thrombolysis.  Results  Compared with control group, serum SOD (P = 0.000) and BI (P = 0.000) in treatment group were significantly higher, while serum MDA (P = 0.001), MMP-9 (P = 0.001), plasma FN (P = 0.000) and NIHSS score (P = 0.006) were significantly lower. In treatment group, 24 h after rt-PA intravenous thrombolysis plus PNS injection, serum MDA (P = 0.000), MMP-9 (P = 0.000) and BI (P = 0.000) were significantly increased, while NIHSS score (P = 0.000) was significantly decreased; 14 d after treatment, serum MDA (P = 0.000) and MMP-9 (P = 0.000) were decreased, serum SOD (P = 0.000) and BI (P = 0.000) were continuously increased, plasma FN (P = 0.000) and NIHSS score (P = 0.000) were continuously decreased. On the 14th day after thrombolysis, hemorrhagic transformation rate of treatment group was lower than that of control group [9 cases (9%) vs 19 cases (19%); χ² = 4.153, P = 0.042]. There was no significant difference in the incidence of adverse drug reactions between 2 groups [14 cases (14%) vs 11 cases (11%); χ² = 0.411, P = 0.521]. Twelve months after thrombolysis, there were 5 cases of death (5% ) in control group and one case (1% ) of death in treatment group. There was no significant difference in the incidence of mortality between 2 groups (χ² = 1.546, P = 0.241). The BI of treatment group was significantly higher than that of control group (88.51 ± 11.49 vs 84.47 ± 9.83; t = 2.451, P = 0.015).  Conclusions  PNS reduces ischemia-reperfusion injury after rt-PA intravenous thrombolysis in patients with acute ischemic stroke. It can reduce the rate of hemorrhagic transformation after rt-PA intravenous thrombolysis and improve the prognosis with good safety.

Key words: Stroke, Brain ischemia, Sanchinoside, Tissue plasminogen activator, Cerebral hemorrhage