大鼠脑缺血再灌注后超早期一过性过度灌注现象的病理生理学机制研究

Pathophysiological mechanisms of ultra-early transient hyperperfusion after cerebral ischemia-reperfusion in rats

目的探讨脑缺血再灌注后自发性一过性过度灌注现象的病理生理学机制。方法52只SD大鼠随机分为假手术组（A组）、缺血2h组（B组）和缺血6h组（C组），B组按再灌注时间分为0h、0．5h、1h、2h、4h、6h、24h组，C组按再灌注时间分为0h、0．5h、1h、2h、24h组，每组4只。各组动物在缺血后再灌注不同时间点行多层螺旋CT灌注成像（CT perfusion imaging，CIPI），扫描完成后立即处死大鼠行光学和电子显微镜检查。结果A组假手术区脑血流灌注参数相对值及光学和电子显微镜结果与对侧无显著差异。随着再灌注时间的延长，B组缺血核心区相对脑血流量（relative cerebral blood flow,rCBF）和相对脑血容量（relative cerebral blood volume，rCBV）逐渐上升，相对平均通过时间（relative mean transit time，rMTr）和相对达峰时间（relative time to peak，rTTP）逐渐下降，再灌注6h后与A组相比无显著差异。光学和电子显微镜显示，B组缺血核心区神经元密度降低，部分细胞体积增大呈空泡变，部分神经元胞体和胞核浓缩。C组随着再灌注时间的延长，缺血核心区rCBF仍维持在较低水平。再灌注0．5h，B组和C组在缺血核心区均出现一过性rCBF和rCBV增高现象，光学和电子显微镜显示此时缺血核心区出现大量凋亡和坏死细胞以及炎症细胞浸润。再灌注6h，B组缺血核心区电镜下可见血管密度增高，微血管怒张。结论CTPI在大鼠大脑中动脉闭塞和再灌注过程中的动态变化与病理学损伤机制具有一定相关性，大鼠脑缺血再灌注后超早期自发性一过性过度灌注现象与灌注损伤后的一过性炎性充血有关。

Objective To investigate the pathophysiological mechanisms of spontaneous transient hyperperfusion after cerebral ischemia-reperfusion in rats. Methods Fifty-two SD rats were randomly allocated into sham-operation （group A）, cerebral ischemia 2-hour （group B）, and cerebral ischemia 6-hour （group C） groups. Group B were redivided into 0-, 0.5-, 1 -, 2-, 4-, 6-, and 24-hour subgroups according to the reperfusion time; group C were redivided into 0-, 0.5-, 1 -, 2-, and 24-hour subgroups according to the reperfusion time （n = 4 in each subgroup）. Multislice spiral CT perfusion imaging （CTPI） was performed at different time points after ischemia-reperfusion in each group. After completing the scanning, the rats were sacrificed immediately for optical and electron microscopy examinations. Results In group A, compared to the contralateral sides, there were no significant differences in the relative value of the cerebral blood flow parameters and the results of optical and electron microscopy in the shamoperated regions. In group B, the relative cerebral blood flow （rCBF） and relative cerebral blood volume （rCBV） in the ischemic core area were increased gradually with the extension of reperfusion time. The relative mean transit time （rMTF） and the relative time to peak （rTIP） were decreased gradually. There were no significant differences compared to group A at 6-hour after reperfusion, The optical and electron microscopy revealed that neuronal density in the ischemic core area in group B were decreased, part of the cell volume enlarged and showed vacuolated changes, and part of the neuronal cell bodies and nuclei shrinked, rCBF in the ischemic core area still maintained lower level with the extension of reperfusion time in group C. The ischemic core area showed the increased transient rCBV and rCBV at 0.5 hour after reperfusion in group B and C. The optical and electron microscopy showed that the ischemic core area presented a large number of necrotic and apoptotic cells, and inflammatory cell infiltration. At 6 hours after reperfusion in group B, the increased blood density was observed under the electron microscope in the ischemic core area, showing capillary engorgement and increased pressure. Conclusions The dynamic changes of CTPI in the process of rat middle cerebral artery occlusion and reperfusion have a certain correlation with the pathological mechanisms of injury. The ultra-early spontaneous and transient hyperperfusion after cerebral ischemia-reperfusion in rats is associated with the transient inflammatory hyperemia after repeffusion injury.