慢性脑缺血小鼠脑血管形态学变化的活体动态观察

In Vivo Morphological Observation of Cortical Vessel in Mice after Chronic Cerebral Hypoperfusion

目的通过建立慢性脑缺血模型,活体动态观察慢性脑缺血后小鼠脑血管形态学变化。方法 Tie2-GFP转基因小鼠7只,左侧颈总动脉永久性结扎结合右侧颈总动脉短暂结扎方法制备慢性脑缺血模型,分别在脑缺血前(D0)和脑缺血后7 d(D7),利用颅窗和激光共聚焦显微镜活体观察小鼠脑缺血前后皮层毛细血管、细动脉及细静脉的变化情况。结果 1缺血前和脑缺血后7 d毛细血管直径分别是(6.62±0.75)μm和(12.50±3.29)μm,脑缺血后毛细血管直径较缺血前扩张(P<0.001);2脑缺血前和脑缺血后7 d毛细血管密度分别为每感兴趣区域(region of interest,ROI)(11.67±1.72)个和每ROI(11.08±2.06)个,差异无显著性(P=0.0583);3脑缺血前和脑缺血后7 d分支毛细血管、网状毛细血管、集合毛细血管及细动静脉直通支直径分别为(6.33±0.94)μm vs(12.36±3.20)μm,(6.87±1.10)μm vs(12.37±2.78)μm,(6.37±0.52)μm vs(11.41±3.10)μm及(6.35±0.92)μm vs(13.91±6.17)μm,脑缺血后均扩张(P分别为<0.01,<0.01,<0.01及<0.05),其中细动静脉直通支扩张最显著;4细静脉直径在D0和D7时分别为(19.59±8.74)μm和(24.81±6.25)μm,脑缺血后细静脉显著扩张(P=0.0054);而细动脉直径在D0和D7时分别是(12.71±2.10)μm和(13.20±3.09)μm,无显著性改变(P=0.2947);5可见细动静脉迂曲、吻合支开放及毛细血管走行改变等血管重构现象。结论慢性脑缺血后皮层血管发生毛细血管扩张、细静脉扩张等改变,这些改变可能有助于调节脑血流量。

Objective To dynamically observe the morphological changes of the cortical vessel in mice after chronic cerebral hypoperfusion through a cranial window.Methods The left common carotid artery ligation and transient right common carotid artery ligation operations were performed on 7 Tie2-GFP transgenic mice.The cortical vessels were observed using confocol microscopy through a cranial window before brain ischemia（DO） and 7days after brain ischemia（D7）.The diameter and density of capillaries,along with the diameter and morphological change of arterioles and venules,were analyzed.Results ①The diameters of capillary before and 7 days after the brain ischemia were（6.62±0.75）μm and（12.50±3.29）μm,which increased significantly after brain ischemia（P〈0.001）.②The capillary densities before and 7 days after the brain ischemia were（11.67±1.72） segments per region of interest（ROI） and（11.08±2.06） segments per ROI.The difference was not significant（P=0.0583）.③The diameters of the precapillary arteriole,post capillary venule,true capillary and thoroughfare channel before and 7 days after the brain ischemia were（6.33±0.94）μm vs（12.36±3.20）μm,（6.87±1.10）μm vs（12.37±2.78）μm,（6.37±0.52）μm vs（11.41±3.10）μm and（6.35±0.92）μm vs（13.91±6.17）μm,respectively,all increased significantly after brain ischemia（P〈0.01,〈0.01,〈0.01,and 〈0.05,respectively）.The most significant dilation was observed in thoroughfare channel.④The diameters of venules on DO and D7 were（19.59±8.74）μm and（24.81±6.25）μm,which increased significantly after brain ischemia（P=0.0054）.However,the diameters of arterioles on DO and D7 were（12.71±2.10）μm and（13.20±3.09）μm,the difference was not significant（P=0.2947）;⑤Capillary remodeling,tortuosity and new anastomosis between venules were observed after brain ischemia.Conclusion The dilation of capillaries and venules were observed after brain ischemia.These changes may contribute to the regulation of cerebral blood flow after chronic cerebral hypoperfusion.