脑内出血早期血肿扩大的分子生物标志研究

目的 前瞻性动态观察脑内出血患者血肿体积的变化与外周血中分子生物标志的相关性，筛选出早期血肿扩大的预警指标，为探索脑内出血早期血肿扩大的可能机制提供理论依据。方法 本研究是一项前瞻性队列研究，连续收集发病6h内的自发性脑出血患者共67例，符合条件者54例，搜集临床资料及血标本，血标本采用酶联接免疫吸附剂测定法检测细胞纤维连接蛋白、基质金属蛋白酶-9、金属蛋白酶抑制因子-1并收集常规实验室指标如纤维蛋白原等，依据血肿扩大标准进行分组分析及早期血肿扩大的多因素分析。结果 67例患者中，发病24h共54人复查颅脑CT，16例出现血肿扩大，血肿扩大的发生率为29.63%，早期血肿扩大患者与血肿未扩大患者在纤维蛋白原水平方面差异具有统计学意义（2.3±0.7 vs 2.9±0.7g/L，P＝0.008），血肿扩大患者与血肿未扩大患者不规则血肿形态发生率方面差异具有统计学意义（50.0% vs 13.2%，P =0.011），相关因素分析显示基质金属蛋白酶-9、纤维蛋白原与脑内出血早期血肿扩大的相关性有统计学意义（OR =12.093，P =0.032；OR =0.162，P =0.041）。结论 纤维蛋白原、基质金属蛋白酶-9与脑内出血早期血肿扩大具有相关性，细胞纤维连接蛋白和金属蛋白酶抑制因子-1未发现明显的相关性。

Study On Molecular Predictive Biomarkers For Early Hematoma Growth of Intracerebral hemorrhage

Objective To study dynamic change of hematoma volume, and the correlation between molecular biological markers of peripheral blood and early hematoma growth in the patients with intracerebral hemorrhage, we aimed to identify the predictive factors of early hematoma growth, we also hope to explore the possible pathophysiologic mechanism of early hematoma growth. Methods It was an open, prospective, single-centered cohort study. 67 spontaneous cerebral hemorrhagic patients within 6 hours after onset were collected consecutively from Apr. 2007 to Dec. 2007, 54 patients were enrolled in the study based on inclusion and exclusion criteria. Clinical data and blood samples were collected. Cellular fibronectin, matrix metalloproteinase-9, tissue inhibitor of metalloproteinases-1 of spontaneous cerebral hemorrhagic 54 patients were measured with commercially available quantitative sandwich enzyme-linked immunosorbent assay kits, laboratory regular measures such as fibrinogen were collected. Patients were divide into two groups by hematoma growth criterion, Potential predictors of early hematoma growth were analyzed by univariate analysis or logistic regression. Results Among all recruited patients who were given CT scan at 24 hours after the onset of ICH, 16 cases appeared hematoma growth, thus the incidence of hematoma growth was 29.63%. Independent-Samples T Test revealed that the fibrinogen level was remarkably lower in hematoma growth patients than that of non-hematoma growth patients（2.3~0.7 vs 2.9~0.7g/L, P=0.008）, and X2 test revealed that the incidence of hematoma growth in patients with irregular-shaped hematoma on initial CT scan was higher than that of patients with a round hematoma（50.0% vs 13.2%, P=0.011）. Multivariate analysis of predictors of hematoma growth revealed that there were two independent risk factors of hematoma growth, while c-Fn was not, MMP-9（OR=12.093, P=0.032） ＆ fibrinogen level（OR=0.162, P=0.041） which may predict the growth of hematoma volume.Conclusion MMP-9 and fibrinogen level were two independent risk factors of hematoma growth, but cellular fibronectin and tissue inhibitor of metalloproteinases-1 were not related to hematoma growth.