实验性脑出血周围组织脑血流变化与脑水肿形成的相关研究

Relationship between alternation of cerebral blood flow and formation of brain edema around the hematoma after experimental intracerebral hemorrhage

目的探讨血肿周围组织脑水肿形成机制及其与局部脑血流变化间的关系,为脑出血临床救治提供实验基础。方法雄性大鼠70只,随机数字抽样法分为注血组和对照组,分别将40μl新鲜自体血或生理盐水通过微量注射泵注入大鼠脑右侧尾状核制备脑出血模型,利用CT灌注成像对大鼠脑出血模型进行动态增强扫描,通过计算机辅助脑灌注成像软件制作大鼠脑CT灌注参数图,对血肿周围局部脑血流量(regional cerebral blood flow,rCBF)、局部脑血容量(regional cerebral bloodvolume,rCBV)和对比剂平均通过时间(mean transit time,MTT)脑灌注参数进行相对值(病侧/健侧)测量,并与血肿周围脑组织水含量进行相关性分析。结果大鼠脑注血后血肿周围组织存在低灌注梯度,血肿周围rCBF呈波动性改变,注血后1h rCBF降至最低,以后逐渐回升,分别于注血后6h和24h2次回升至峰值,并随后再度下降;血肿周围rCBV在注血后1h降至最低,随后逐渐增加,并于注血后24h增加至峰值;血肿周围脑组织水含量在注血后24h最高,并延续至72h;血肿周围脑组织水含量与血肿边缘区rCBV具有明显相关性,r=0.372(单侧),P<0.05。结论血肿周围组织脑水肿的形成是血脑屏障破坏、细胞毒性水肿及渗透性活性物质共同作用的结果,脑出血早期rCBF下降以及rCBV代偿性增加在脑出血血管源性脑水肿形成中发挥着重要作用,CT灌注成像是活体下研究血肿周围脑血流变化与脑水肿形成机制较为理想的方法。

Objective To investigate the mechanism of brain edema formation around the hematoma and the relationship between the formation of brain edema and the changes of regional cerebral blood flow after intracerebral hemorrhage （ICH） in rats, and to provide experimental basis for the clinical treatment of ICH. Methods Seventy male Sprague-Dawley rats were randomly divided into ICH groups and shamoperated groups. ICH was produced by microinjection of 40 ul fresh autologous blood or saline into the right caudatum. Dynamic CT perfusion imaging was performed, and the parameters of regional cerebral blood flow （rCBF） , regional cerebral blood volume （ rCBV）, and mean transit time （MTT） around the hematoma were calculated respectively. Then the rats were sacrificed, and the water content, sodium, potassium, and calcium concentrations were measured respectively. The correlative study between the water content and rCBF and rCBV were carried out. Results The gradient of perihematomal hypoperfusion was revealed on CT perfusion maps in ICH groups. The alternation of rCBF around the hematomas were fluctuated, and rCBF reduction was most pronounced at 1 hour afer ICH, then the rCBF gradually returned, reaching the peaks at 6 hours and 24 hours after ICH, respectively. In the meantime, rCBV reduction around the hematoma was most pronounced at 1 hour after ICH. Then the rCBV gradually increased, and reaching the peak at 24 hours. The water contents were gradually increased in the ipsilateral basal ganglia in the animals sacrificed at 6, 24, and 72 hours. The accumulation of water was at its peak at 24 hours, and remained in the animals sacrificed at the 72 hours. The perihemorrhagic water contents correlated significantly with rCBV surrounding hematomas, r = 0.372 （ one-tailed）, P 〈 0.05. Conclusion The perihemorrhagic brain edema results from the common effects of the blood-brain-barrier disruption, cytotoxic edema, and the accumulation of osmotically active substances. The rCBF reduction occured in the early stage of ICH and the rCBV compensatory increase play important roles in producing vasogenic edema. Perfusion CT and its parameter analysis is a suitable method in the study of the relationship between the formation of brain edema and the changes of regional cerebral blood flow after intracerebral hemorrhage in vivo.