蛛网膜下腔出血脑脊液不对称二甲基精氨酸水平与脑血管痉挛的相关性研究

Correlation of cerebral spinal fluid ADMA with subarachnoid hemorrhage and cerebral vasospasm in rabbits

目的观察蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后脑脊液中不对称二甲基精氨酸(ADMA)和NO水平的动态变化,探讨ADMA含量与脑血管痉挛(cerebral vasospasm,CVS)的关系。方法采用枕大池二次注血法建立SAH后脑血管痉挛动物模型,分别于术前,术后1、4、7d行经颅多普勒超声(transcranial Doppler sonography,TCD)检查测定基底动脉脑血流速度,应用酶联免疫分析法(ELISA)和硝酸还原酶法测定不同时间脑脊液中ADMA和NO含量。结果①SAH后脑脊液中ADMA浓度显著高于注血前正常水平(P<0.01),术后4d达到峰值后逐渐下降,而脑脊液中NO水平注血后4d逐渐下降至最低值(P<0.01);②SAH后血管痉挛程度逐渐加重,动脉血流第4天达到最大值后逐渐缓解,与ADMA水平时相表达一致;③SAH后脑脊液中ADMA浓度变化趋势与基底动脉血流速度相应,SAH后第4天脑脊液中ADMA浓度与NO水平呈显著负相关(r=-0.950,P<0.01),与基底动脉血流速度呈显著正相关(r=0.953,P<0.01)。结论SAH后脑血管痉挛程度与脑脊液中ADMA表达含量密切相关,SAH后脑脊液中ADMA可能通过调控NO生成水平参与了迟发性脑血管痉挛发生、发展的过程。

Objective To investigate the dynamical changes of asymmetric dimethylarginine （ADMA） and nitric oxide （NO） in the cerebral spinal fluid （CSF） after subarachnoid hemorrhage （SAH）, and access the relationship between the concentrations of ADMA and cerebral vasospasm （CVS）. Methods An experimental cerebral vasospasm model was established by twice injections of fresh autologous arterial blood into the cisterna magna of 32 white rabbits. Another 8 rabbits receiving sham operation served as sham control. The velocity of basilar artery （BA） was measured by transcranial Doppler（TCD） before the injection and on the 1st, 4th, 7th day after twice injections. At the same time, the CSF concentrations of ADMA and NO were measured by ELISA and nitrate reductase method respectively. Results The concentrations of ADMA in CSF was increased significantly after the injection than that before injection（P 〈 0. 01 ） , and was decreased gradually after reaching the highest level on the 4th day. However, the trend of NO were quite opposite （P 〈 0. 01 ）. The degrees of CVS became serious after SAH and then was relieved gradually after reaching the peak flow velocity of basilar artery on the 4th day. The change of the ADMA in the CSF was synchronal with the velocity of basilar artery. On the 4th day after twice injections, the concentrations of ADMA were correlated negatively with NO level（ r = -1. 829, P 〈0. 01 ）, but positively with the velocity of basilar artery（r =0. 863, P 〈0.01 ）. Conclusion The degree of cerebral vasospasm after subarachnoid hemorrhage is positively related to the concentration of ADMA in cerebral spinal fluid, so measuring the concentrations of ADMA in cerebral spinal fluid after subarachnoid hemorrhage may be helpful in evaluating the development of delayed cerebral vasospasm.