重组人促红细胞生成素对脑梗死患者的脑保护作用

Cerebral protective effect of erythropoietin on patients with cerebral infarction

目的观察重组人促红细胞生成素(rHu-EPO)治疗脑梗死的疗效。方法根据发病时间,将217例脑梗死患者分为急性期组(发病≤48 h)113例和亚急性期组(发病>48 h至5 d)104例。每组又按抽签法随机分为2个亚组,A1组(急性期对照组)50例,A2组(急性期治疗组)63例;B1组(亚急性期对照组)50例,B2组(亚急性期治疗组)54例。各组患者均接受基础治疗,A2组和B2组辅助rHu-EPO治疗,3000 U/次,皮下注射,1次/3 d,共2次。治疗前和治疗后第1、6个月时,采用改良爱丁堡+斯堪的那维亚评分(MESSS)评价神经功能缺损状况,检测治疗后14 d时血清神经元特异性烯醇化酶(NSE)水平,并观察血清一氧化氮(NO)变化。结果①治疗后第1、6个月A2组患者MESSS分别为16±6、10±7,A1组分别为21±8、14±4,两组间第1、6个月比较,差异均有统计学意义(P<0.01);治疗后14d,A2组NSE为(10.0±3.6)μg/L,NO为(41±6)μmol/L,A1组NSE为(12.4±5.8)μg/L,NO为(47±10)μmol/L,两组比较,P<0.05和P<0.01。②第1、6个月B2组与B1组间MESSS差异无统计学意义(均P>0.05);14 d时两组间NO水平相近(P>0.05),但两组间NSE比较[(12.0±5.1)、(14.3±4.8)μg/L],差异有统计学意义(P<0.05)。③第1、6个月A2组与B2组间MESSS比较,差异有统计学意义(均P<0.001)。结论 EPO能改善脑梗死急性期患者的近期预后,具有脑保护作用;但对亚急性期患者的预后,未显示有改善作用。短期应用rHu-EPO,无明显不良反应。其治疗机制之一可能是抑制了NO过量生成。

Objective To observe the efficacy of recombinant human crythropoietin （rHu-EPO） in the treatment of cerebral infarction. Methods Two hundred seventeen patients with cerebral infarction were divided into an acute phase group （onset time ≤ 48 hours; n = 113 ） and a subacute phase group （onset time from 〉 48 hours to 5 days; n = 104） according to the time of onset, Each group was randomly redivided into 2 subgroups according to drawing lots： A1 group （acute phase control group） 50 patients; A2 group （acute phase treatment group） 63 patients; B1 group （subacute phase control group） 50 patients; B2 group （subacute phase treatment group） 54 patients. The patients in all groups received the basic therapy, A2 and B2 groups also received the adjuvant therapy with rHu-EPO. The modified Edinburgh-Scandinavia stroke scale （MESSS） before the treatment and at 1 and 6 months after the treatment, and the serum neuron specific enolase （NSE） levels at day 14 were evaluated. The changes of serum nitric oxide （NO） were also observed. Results （1） MESSS in the acute phase treatment group at 1 and 6 months were 16 ± 6 and 10 ± 7, respectively; in the acute phase control group were 21 ± 8 and 14 ± 4, respectively. There were significant differences between the two groups at 1 and 6 months （P 〈 0.01 ）. NSE and NO levels at day 14 in the treatment group were 10.0 ± 3.6 μg/L and 41 ± 6 μmol/L, respectively; the NSE and NO levels in the control group were 12.4 ±5.8 μg/L and 47 ± 10 μmol/L, respectively. The treatment group compared with the control group（P 〈0.05 and P 〈0.01 ）. （2）There was no significant differences in MESSS between the subacute treatment group and the control group at 1 and 6 months （P 〉 0.05 all） ; the NO levels in both groups at the 14 day were similar （P 〉 0.05）, however, there was significant difference in NSE between the two groups （ 12.0 ± 5.1,14.3 ± 4.8 μg/L, P 〈 0. 05 ）. （3）There were significant differences in MESSS between the acute phase treatment group and the subacute phase treatment group at 1 and 6 months （P 〈 0. 001 all）. Conclusion EPO has cerebral protective effect. It can improve the short-term prognosis of patients with acute cerebral infarction, however, it does not show any effect on the prognosis of patients with subacute cerebral infarction. There is no significant adverse reaction for short-tern application of rHuEPO. One of its therapeutic mechanisms may be the inhibition of NO over production.