粒细胞集落刺激因子治疗急性脑梗死的疗效及安全性研究

Granulocyte Colony-stimulating Factors in Acute Ischemic Stroke:A Study of Effect and Safety

背景脑梗死除了超早期溶栓外尚无其他特效疗法,近年有研究发现粒细胞集落刺激因子(G-CSF)可改善脑梗死的预后,但有关其剂量、疗程、用药时机及安全性等众多问题仍需探索。目的探讨G-CSF治疗急性脑梗死的有效性和安全性。方法选择2011—2012年在我院神经内科住院的脑梗死患者,采用前瞻性研究方法,将发病7 d内且梗死体积>15 ml的脑梗死患者按随机数字表法分成两组:试验组(G-CSF组)皮下注射G-CSF 300μg/次,2次/d,共5 d;对照组皮下注射0.9%氯化钠溶液2 ml/次,2次/d。比较两组患者入组时及入组1、2、3个月时美国国立卫生研究院卒中量表(NIHSS)评分和日常生活能力评定量表(Barthel指数)评分。G-CSF组第1～8天监测CD+34细胞数、血小板计数、凝血功能、肝肾功能等指标,观察G-CSF对上述指标的影响。结果 G-CSF组最终纳入统计40例,对照组纳入统计42例。G-CSF组内重复测量的方差分析显示,第1～8天各时间点CD+34细胞数和白细胞计数(WBC)间差异有统计学意义(F=83.25、395.72,P=0.00),第6天均达到高峰,停用G-CSF后(第7、8天)较第6天下降(P<0.05)。第6天时丙氨酸氨基转移酶(ALT)水平达到高峰,但仍在参考范围内(<50 U/L),停用G-CSF后(第7、8天)较第6天下降(P<0.05)。第6天时D-二聚体水平较第1天升高,停用G-CSF后(第7、8天)仍较第6天升高(P<0.05)。入组2、3个月时两组NIHSS评分间差异有统计学意义(P<0.05),两组不同时间点Barthel指数评分分级间差异均无统计学意义(P>0.05)。G-CSF组19例发生胃肠道反应,15例发生骨骼肌肉疼痛,12发热,1例患者在住院第26天时发生左腋静脉堵塞导致左上肢肿胀。对照组没有发生血栓性栓塞事件。结论发病7 d内且梗死体积>15 ml的脑梗死患者皮下注射G-CSF(300μg/次,2次/d)能改善短期预后,但可能增加血栓栓塞事件的风险。

Background For cerebral infarction （CI）, there is no effective therapy except ultra- early thronlbolysis yet. Recent studies have found that granulocyte colony- stimulating factors （G- CSF） can improve CI prognosis, but problems such as its dose, duration, timing of medication and safety still need to be explored. Objective To explore the efficacy of G - CSF on acute CI and its safety. Methods A total of 82 CI patients, from 2011-2012, with infarct volume 〉 15 ml starting within 7d were divided randomly into groups G - CSF （ subcutaneous injection of G - CSF, 300 μg/time, 2 twice/d, 5 d） , control （subcutaneous injection of O. 9% sodium chloride solution, 2 ml/time, 2 times/d）. Scores of US National Institutes of Health Stroke Scale （NIHSS） and Rating Scale of Activity of Daily Living （Barthel Index） were compared between 2 groups in months 1, 2, 3. CD34＋ cell count and platelet count, coagulation function, liver and kidney functions and other indicators were monitored in G - CSF group on days 1 - 8 and the effect of G - CSF on the above indicators observed. Results There were 40 cases finally inclued in G - CSF group, 42 cases in control group. By analysis of variance, there was significant difference in CD34＋, WBC between each time point of days 1 - 8 in G - CSF group （ F = 83.25, 395.72, respectively, P = 0.00） , reaching the peak on days 6 and descending rapidly after stopping G - CSF （ on days 7, 8 ） （ P 〈 O. 05 ）. ALT got to the peak on days 6, but within the normal range （ 〈 50 U/L） , and were lower after stopping G - CSF （ on days 7, 8 ） than on days 6 （ P 〈 O. 05 ）. D - dimer level was higher on days 6 than on day 1, and higher than after stopping G - CSF （ on days 7, 8 ） （ P 〈 0. 05 ）.There was significant difference in NIHSS scores between 2 groups in months 2, 3 （P 〈 0. 05 ）, but no in Barthel Index score level at varying time points （P 〉0. 05 ）. In G - CSF group, 19 had gastrointestinal reactions, 15 had musculoskeletal pains. Conclusion G - CSF can improve the short - term prognosis of CI patients with infarct volume 〉 15 ml starting within 7 d, but may increase the risk of thromboembolic events.