慢性脑低灌注后失交感神经支配对脑动脉生成的影响

Sympathetic denervation impairs cerebral arteriogenesis after chronic cerebral hypoperfusion in rats

目的探讨在慢性脑低灌注情况下,失交感神经支配对脑动脉生成的影响。方法通过结扎右侧颈总动脉8周建立慢性脑低灌注模型,外科手术法去除同侧颈上交感神经节。将84只健康的成年雄性SD大鼠用随机数字表法分为动脉结扎+去神经组(联合组)、动脉结扎组、去神经组和假手术组(每组21只)。术后8周,将每组动物随机分成A、B、C 3个亚组(每组7只),分别行乳胶灌注、大脑中动脉永久性阻塞以及免疫组化染色。结果联合组右侧软脑膜吻合支直径明显小于动脉结扎组,大于去神经组和假手术组(P<0.05);联合组右侧Willis动脉环直径明显小于动脉结扎组(P<0.05);免疫组化染色结果显示,联合组右侧软脑膜吻合支管壁厚度小于动脉结扎组(P<0.05);8周后行永久性大脑中动脉阻塞实验,联合组显示大脑中动脉区的脑血流值与基线值的比值小于动脉结扎组(P<0.05);神经行为学评分结果显示联合组评分高于动脉结扎组(P<0.05);同时TTC染色显示联合组脑梗死体积百分率大于动脉结扎组(P<0.05)。结论脑血管失交感神经支配损害了慢性脑低灌注时的脑动脉生成。

Objective To determine the effect of sympathetic denervation on cerebral arteriogenesis in rat model of chronic cerebral hypoperfusion and investigate the underlying possible mechanism. Methods The SD rat model of chronic cerebral hypoperfusion was established by right common carotid artery ligation for8 weeks,while denervation was performed by surgical removal of the ipsilateral superior cervical sympathetic ganglion. A total of 84 healthy adult male SD rats were randomly divided into 4 groups,that is,model and denervation group（ n = 21）,artery ligation group（ n = 21）,denervation group（ n = 21） and sham-operation group（ n = 21）. In 8 weeks after surgery,the rats in each group were further randomly assigned into 3 subgroups,that is,sub-group A（ n = 7）,sub-group B（ n = 7）,and sub-group C（ n = 7）. The diameter of leptomeningeal collateral vessels and Willis circle artery were observed in sub-group A after latex perfusion;the rats in sub-group B were subjected to permanent right middle cerebral artery occlusion. Cortical cerebral blood flow was measured. Cerebral infarct volume was tested by TTC staining in 24 h post-operatively.Immunohistochemical staining was carried out in sub-group C to observe the structural changes of the right leptomeningeal collateral vessels. Results The diameters of right leptomeningeal collateral vessels and Willis circle artery were both significantly smaller in the model and denervation group than the artery ligation group（ P 〈 0. 05）,and obviously larger than in the denervation group（ P 〈 0. 05） and sham-operation group（ P 〈0. 05）. Immunohistochemical staining showed the thickness of right leptomeningeal collateral vessels was obviously decreased in the model and denervation group compared with the artery ligation group（ P 〈 0. 05）,but remarkably increased than the denervation group（ P 〈 0. 05） and the sham-operation group（ P 〈 0. 05）.In 8 weeks after permanent right middle cerebral artery occlusion,the ratio of cerebral blood flow to basic level was significantly lower in the model and denervation group than the artery ligation group（ P 〈 0. 05）,but markedly higher than in the denervation group（ P 〈 0. 05） and the sham-operation group（ P 〈 0. 05）.Neurological function scoring indicated that scores were significantly higher in the model and denervation group than the artery ligation group（ P 〈 0. 05）,but obviously lower than in the denervation group（ P 〈 0. 05） and the sham-operation group（ P 〈 0. 05）. TTC staining showed the cerebral infarct volume was significantly larger in the model and denervation group than the artery ligation group（ P 〈 0. 05）,and remarkably smaller than in the denervation group（ P 〈 0. 05） and the sham-operation group（ P 〈 0. 05）. Conclusion Sympathetic denervation impairs the cerebral arteriogenesis in rats with chronic cerebral hypoperfusion.