动脉内灌注罂粟碱治疗脑血管痉挛的实验研究

The Experimental Study of Intra-arterial Papaverine Infusion for Cerebral Vasospasm

目的 研究不同时间段动脉内灌注罂粟碱 (IAP)治疗蛛网膜下腔出血 (SAH)后脑血管痉挛 (CVS)的效果 ,观察脑水肿及病理变化 ,并测定血清中IL - 6及TNF -α含量的变化。方法 经额颞开颅 ,Willis环前部 2次注血制成兔SAH模型。经DSA脑血管造影测量基底动脉 (BA)的直径来评价CVS的严重程度 ,病理检查BA的形态学变化 ;测定脑组织中水含量的变化 ;测定血清中IL - 6及TNF -α的含量。治疗分别于SAH后 3d及 7d由颈内动脉 (ICA)灌注罂粟碱 ,同时进行上述检查。结果 该模型引起的脑血管痉挛发生率达 10 0 %。脑组织中水含量在SAH后有不同程度升高 ,BA也发生不同程度病理改变。血清中IL - 6含量 3d时有明显升高 ,7d时达高峰 ,至SAH后 14d时仍维持较高水平 ;TNF -α含量在各时间段变化不明显。IAP治疗后 ,痉挛动脉有明显的扩张 ,早期治疗效果明显 ,治疗组血清中IL - 6含量较同期SAH组低 ,而TNF -α含量在各组中无明显差异。结论 IAP对治疗SAH后CVS疗效确切 ,能显著扩张血管 ,减轻缺血性脑水肿及病理变化 ,SAH后早期治疗的效果更为明显。血清中IL - 6水平与CVS程度呈正相关 ,提示免疫炎症反应与CVS的发生存在一定关系。早期联合应用免疫抑制剂 ,可望进一步提高IAP治疗CVS的疗效。

Objective To study the effectiveness of intra-arterial infusion of papaverine (IAP) for cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH), observe the changes of brain edema and histological, analyze of IL-6 and TNF-α levels in serum and study the correlation between CVS and cytokine.Methods The primary SAH model of rabbit was maded by which the blood was introduced to anteriorsite of the circle of willis by frontotemporal craniotomy for two times. The diameter of basilar artery(BA) was detected by cerebral angiography. Examined the morphologic changes of BA in lightscopy; The water content of brain was measured by the wet and dry weight method. The levels of IL-6 and TNF-α in serum were analyzed . The treatment was maded by intra-interal artery(ICA) infusion of PPV on the third and seventh day after SAH and examination conducted as previously described. Results The incidence of CVS reached 100% in this model. The histological examination demonstrated the obvious morphologic changes in the arterial wall of BA. The water content of brain is increased in different degree. On the third day after SAH, the levels of IL-6 in serum were obviously higher then that in control samples.The peak values on the seventh day ,and on the 14th day after SAH they were higher than the normal level.The level of TNF-α in serum did not changed in various periods.After treated with PPV, the spasm vascular has dilatated obviously,The level of IL-6 in the treated group is lower than that in SAH group at the same time.And there was no obvious difference in TNF-α in serum after treatment.Conclusion IAP is effective in treatment of CVS after SAH,which can dilatate vascular obviously and reduce the ischemical brain edema and histologic changes.The effectiveness of IAP is better on the third day following SAH than later.The level of IL-6 in serum positively correlated with CVS,which suggests the immuno-inflammatory response takes a role in the mechanism of CVS.It is suggested that CVS can be treated effectively with combination of intra-arterial,infusion papaverine and using immunosuppresant in the early phase.