蛛网膜下腔出血致脑深静脉痉挛的实验研究

The cerebral vasospasm is the most important factor for the prognosis of patients who suffer subarachnoid hemorrhage (SAH). Clinically, the cerebral vasospasm is treated by anti-arterial vasospasm therapy. However, the long-term outcome in these patients have not be ameliorated effectively. Our studies have confirmed that cerebral veins have smooth muscle, which denote that the cerebral venous vasospasm can be induced by SAH. The cerebral arterial vasospasm induces the cerebral ischemia, while the cerebral venous vasospasm induces the cerebral edema. Each kind of the vasospasm has its own therapy. The vasospasm of deep cerebral veins is more prone to cause cerebral edema as they are few collateral circulations. In order to prove our hypothesis, the following experiments are designed. Firstly, the rabbits models of SAH are established, and the diameter of deep cerebral veins and cerebral arteries are observed by neuroimaging before modeling and after modeling in different time-points, to find whether the vasospasm of deep cerebral veins is occur or not, and to elucidate the relation between the venous and arterial vasospasm. Secondly, the change of cerebral veins smooth muscle in different time points is observed by pathology and cell culture techniques, to clarity the mechanisms of vasospasm of deep cerebral veins induced by SAH. Finally, the radiology and clinical informations of SAH patients are collected, to identify the vasospasm of deep cerebral veins spasm which is surely occur in the clinical patients. The datas generated from this study may provide new theoretical basis for the occurrence and therapy of cerebral vasospasm after SAH.

蛛网膜下腔出血后脑血管痉挛的发生是影响患者预后的重要因素，目前临床主要针对脑动脉痉挛进行治疗，但患者的长期预后并未得到有效改善。课题组前期证实脑静脉含有平滑肌，具有痉挛发生的形态学基础，即蛛网膜下腔出血还可能导致脑静脉痉挛，此时脑血液回流受阻、引起脑水肿，这与脑动脉痉挛引起的缺血性脑梗死完全不同。脑深静脉侧枝循环少，如发生痉挛更易致脑水肿。为此，本课题拟：①建立兔蛛网膜下腔出血模型，利用影像学技术对比观测出血后不同时间点脑动脉和脑深静脉管径的变化，探明脑深静脉是否发生痉挛及其与脑动脉痉挛间的关系；②采取病理学和细胞培养技术观察出血后不同时间点脑深静脉血管平滑肌的变化规律，阐明蛛网膜下腔出血致脑深静脉痉挛发生的具体机制；③收集蛛网膜下腔出血患者的临床和影像学资料，在活体进一步验证蛛网膜下腔出血会导致脑深静脉痉挛。研究结果能够为蛛网膜下腔出血后脑血管痉挛的发生及治疗提供新的思路和理论依据。

脑血管痉挛是蛛网膜下腔出血患者的常见并发症，是影响患者预后的重要因素。以前的研究集中在脑动脉痉挛上，然而采取针对性的治疗后，患者的长期预后并未得到有效改善。本课题结合前期研究结果，提出了蛛网膜下腔出血可能导致脑深静脉痉挛的假说。与脑动脉痉挛时脑缺血、引起脑梗死不同，脑深静脉痉挛首先会出现脑血液回流受阻、引起脑水肿。. 本研究首先结合超声引导穿刺技术，建立了高效而又低死亡率的兔脑血管痉挛模型；接着利用无创性的磁共振血管成像技术，观察了出血后不同时间点脑动脉和脑深静脉管径的变化，证实兔蛛网膜下腔出血可导致脑深静脉痉挛；然后采用组织学和分子生物学技术检测了出血后不同时间点脑深静脉血管平滑肌的变化，阐明了兔脑深静脉痉挛发生的机制；最后收集活体影像学资料，阐明了正常人和蛛网膜下腔出血患者脑深静脉的变化规律，证实人蛛网膜下腔出血后同样会发生脑深静脉痉挛。. 结果显示，①采用枕大池二次注血建立脑血管痉挛模型，传统的徒手穿刺组死亡率为23%，超声引导穿刺组未见动物死亡。造模后5 d，基底动脉管径较造模前明显狭窄，超声引导穿刺组狭窄更加明显，重度狭窄的比例显著高于徒手穿刺组。8%的徒手穿刺组未发现明显血管痉挛。②与出血前相比较，出血后大脑内静脉和基底静脉显著变细，大脑大静脉管径变化不明显。出血后1~11 d不同时间点的数据显示，脑深静脉血管变细的时间与基底动脉不一致。③出血后，基底静脉出现管腔狭窄，管壁不完整等表现。与出血前相比较，出血后α-SMA蛋白含量上升、vWF蛋白含量下降，以造模后5 d变化最明显，相应基因检测结果类似。出血后，脑深静脉内的TXA2的含量上升，且高于脑动脉内含量，血管壁中的TXA2受体蛋白与基因含量上升。④无创性的CT和MR影像检查技术显示脑深静脉及相关结构效果满意。与对照组相比较，蛛网膜下腔出血的急性期，大脑内静脉和基底静脉管径显著变细，大脑大静脉管径变化不明显。. 目前，临床上脑动脉收缩痉挛主要采用增加脑灌注压和扩血管治疗，而脑静脉收缩痉挛只能选择扩血管治疗，由于其静脉回流不畅，采用增加脑灌注压的治疗措施，将导致脑水肿进一步加重。因此，课题组认为，临床在蛛网膜下腔出血患者中同时行脑动脉和脑静脉造影非常有必要。影像学检查的结果将会对于患者治疗方案的选择起着非常重要的指导意义。