脑蛋白水解物治疗急性缺血性脑卒中疗效及安全性的meta分析

Efficacy and safety of cerebroprotein hydrolysate in the treatment of acute ischaemic stroke: a meta-analysis

目的:系统评价脑蛋白水解物治疗急性缺血性脑卒中的有效性和安全性。方法:系统检索Pubmed、Sino Med、知网、维普和万方数据库中脑蛋白水解物治疗脑梗死相关临床随机对照试验(RCT)研究文献,2位研究者独立评价纳入研究方法学水平,筛选并提取文献资料数据后,使用Revman5.3和Stata 12.0软件对提取数据进行合并处理。结果:共纳入31个RCT(3203例患者)进行meta分析。结果显示,脑蛋白水解物可用于脑梗死的治疗。(1)临床有效率:与空白对照比较,脑蛋白水解物可提高临床有效率,RR=1.22,95%CI[1.17,1.28];与依达拉奉比较,脑蛋白水解物未提高临床有效率,RR=0.75,95%CI[0.67,0.84];与胞二磷胆碱比较,脑蛋白水解物可提高临床有效率,RR=1.21,95%CI[1.10,1.32]。(2)神经功能缺损评分:与空白对照比较,用药2周能显著改善神经功能缺损,降低MESSS评分,WMD=-4.44,95%CI[-6.55,-2.34];降低NIHSS评分,WMD=-2.21,95%CI[-3.56,-0.85]。(3)日常生活能力评分:与空白组比较,用药4周改善患者日常生活能力,提高BI评分,WMD=4.34,95%CI[3.15,5.53];(4)血液流变学指标:与空白对照比较,能显著降低血液黏度(高、低切变率)、纤维蛋白原含量,分别为MD=-0.66,95%CI[-0.89,-0.43],MD=-1.28,95%CI[-1.86,-0.69],MD=-0.75,95%CI[-1.19,-0.31]。安全评价:7个RCT报告患者使用脑蛋白水解物的不良反应事件,均为轻度不良反应,可自行缓解,提示脑蛋白水解物良好的安全性。结论:使用脑蛋白水解物治疗脑梗死(急性缺血性脑卒中)患者,具有提高临床疗效、促进神经功能恢复、改善血液高凝状态的治疗效果,且用药安全性良好。本次meta研究结论受纳入研究数量和原始研究本身偏倚影响,应随着更多高质量临床研究结果的纳入,不断更新meta分析结果以增加评价结果的稳健性。

Objective： To systematically review the efficacy and safety of cerebroprotein hydrolysate for patients with cerebral infarction. Methods： We systematically searched several databases, including Pub Med, Sino Med, CNKI, VIP and Wan Fang databases for randomized controlled trials（RCTs） of cerebroprotein hydrolysate administered for patients with cerebral infarction. 2 reviewers assessed methodology level independently,screened and extracted the datafrom the literature, and then Revman 5.3 and Stata 12.0 software were adopted to merge application of extraction data.Results：31 RCTs involving 3203 patients with cerebral infarction were included.The results of the meta-analysis of cerebroprotein hydrolysate administered in patients with cerebral infarction showed that, compared with the blank control group, cerebroprotein hydrolysate could significantly increase the efficacy rate, RR=1.22, 95%CI（1.17 to 1.28）. Compared with the edaravone group, the efficacy rate was significantly lower in the cerebroprotein group, RR=0.75, 95%CI（0.67 to 0.84）. Compared with the citicoline group, the efficacy rate was significantly higher, RR=1.21, 95%CI（1.10 to 1.32）. Compared with the blank control group, cerebroprotein hydrolysate used for 2 weeks could significantly decrease the MESSS and NIHSS average scores（both were neurological deficit scores）, MESSS WMD=-4.44, 95%CI（-6.55 to-2.34） and NIHSS score WMD=-2.21, 95%CI（-3.56 to-0.85）. Compared with the blank control group, cerebroprotein hydrolysate used for 4 weeks could significantly increase the BI score（A scale of the ability of daily life）, BI WMD=4.34, 95%CI（3.15 to 5.53）.In terms of hemorheological indexes, compared with the blank control group, the blood viscosity（high and low shear rates） and the fibrinogen content of cerebroprotein hydrolysate group is significantly lower, high shear rates： MD=-0.66, 95%CI（-0.89 to-0.43）, low shear rates：MD=-1.28,95%CI（-1.86 to-0.69））, fibrinogen： MD=-0.75, 95%CI（-1.19 to-0.31）. In terms of safety, 7 trials reported adverse reaction incidences in cerebroprotein hydrolysate group, however all symptoms were mild and relieved spontaneously,indicating adequate safety.Conclusion： Cerebroprotein hydrolysate could significantly improve the clinical efficacy, the recovery of nerve function and hypercoagulable state of blood of patients suffered from cerebral infarction（acute ischaemic stroke） with sufficient safety. However, this conclusion is limited by the quantity and methodological quality of the included studies,more high-quality clinical trials should be included to gradually obtain the more reliable evaluation results.