稳定型高流量脑动静脉畸形动物模型的建立

Establishment of stable cerebral arteriovenous malformation model in swine

目的探讨建立稳定性、高流量的脑动静脉畸形(AVM)动物模型的方法,为人脑AVM的临床研究提供帮助。方法将实验用小型猪40头按随机数字表法随机分实验组和对照组,每组20头。以猪的颅底微血管网(RM)为畸形血管团,行左侧咽升动脉(L-APA)与左侧颈外静脉(L-EJV)的端端吻合,结扎同侧颈外动脉(L-ECA)、L-APA降支和左侧枕动脉(L-OA)降支。实验组造模前1 d及造模后即刻、造模后7、14、21和28 d股静脉注射一氧化氮合酶抑制剂L-NAME(250 mg/kg)。造模术前1 d及造模后即可、造模后21 d、28 d、2月和3月行脑血管造影检查和经颅多普勒超声(TCD)检测右侧颈总动脉(R-CCA)、右侧APA(R-APA)、右侧颈外动脉(R-ECA)、右侧颈内动脉(R-ICA)、RM、左侧颈内动脉(L-ICA)、L-APA和L-EJV端端吻合的引流静脉,测量平均峰值血流速度(APV)及峰值流速差、频谱、博动指数(PI)、脑血流量(CBF)、血流方向(BD)以及R-APA压力、L-APA-EJV压力和二者之间压力差。结果两组均造模成功,BD由右侧流向左侧。实验组APV峰值流速差、频谱、PI和CBF明显高于对照组(P<0.05),实验组R-APA压力明显增加(P<0.05),L-APA-EJV压力明显减低(P<0.0)。结论以R-CCA、R-APA、R-ECA、R-L-ICA为供血动脉、以RM为畸形血管团、以L-APA-EJV为引流静脉可成功建立稳定性、高流量脑AVM动物模型。

Objective To provide the animal model for the study of cerebral arteriovenous malformation （AVM）. Methods Forty swine were randomly divided into the experimental （n=20） and control （n=20） group. The fete mirabile of the skull base in the swine served as the malformation mass. The anastomosis of the end of left ascending pharyngeal artery （APA） and the end of the left external jugular vein （ETV） was performed in both the groups, in which the left external artery （ECA） and the descending braehes of both the left APA and occipital arteries were ligated. The injection of L-NAME （nitric oxide inhibitors, 250 mg/kg） into the femoral vein was performed group before the operation and immediately, and 7, 14, 21 and 28 days after the operation in the experimental group. The cerebral angiography was performed and the dynamics of the cerebral blood flow was determined by 3 dimensional transcranial Doppler Sonography before the operation and immediately, 21 and 28 days, and 2 and 3 months after the operation in both the groups. Results The blood pressure of right APA, ramus anatomotics, anatomosed artery and internal carotid artery （ICA）, and pressure difference between the left APA and EJV were significantly higher in the experimental group than those in the control group after the operation （P〈 0.05）. The average peak velocities of the arteries feeding to AVM and the veins draining from the AVM were significantly higher in the experimental group than those in the control group after the operation （P〈0.01）. The pulse index and cerebral blood flow of the arteries feeding to the AVM and veins draining from the AVM were significantly higher in the experimental group than those in the control group after the operation （P〈0.01）. Conclusion The cerebral AVM which was supplied with blood by the right CCA, APA and ECA and both the side of ICA and was drained from by the left APA and EJA is successfully established. The AVM model is stable and is of high blood flow.