罂粟碱明胶微球对脑血管痉挛的治疗作用

Efficacy of papaverine-gelatin microspheres treatment on vasospasm following subarachnoid hemorrhage in vivo

目的:尽管治疗蛛网膜下腔出血后脑血管痉挛方法有扩容、升压、血液稀释以及罂粟碱扩血管,但有些患者难以耐受或无效。需要较少副作用的治疗措施。尤其是局部靶向用药。文中在术中将罂粟碱明胶微球植入痉挛的脑血管周围,明确罂粟碱控释系统对脑血管壁的保护机制。方法:制备兔的2次注血的蛛网膜下腔出血(SAH)模型,使用罂粟碱明胶微球注入兔的自体枕大池注血模型,以7 d时在DSA造影下基底动脉血管直径变化和透射电镜下血管壁病理改变为观察指标,判断治疗效果。结果:A组(对照组)、B组(SAH模型组)、C组(空白明胶微球组)及D组(治疗组)。基底动脉血管直径分别为(1.06±0.11)、(0.52±0.24)、(0.46±0.16)和(0.92±0.25)mm。D与B、C组间差别有统计学意义(P<0.05)。同时,透射电镜下,A、D组血管壁无明显病理变化。结论:在蛛网膜下腔早期鞘内注入罂粟碱缓释明胶微球即对实验性血管痉挛有治疗效果又对血管壁有保护作用。

Objective： Although subarachnoid hemorrhage （SAH）-induced cerebral vasospasm can be treated by intravascular volume expansion, hemodilution, hypertension induction and the use of papaverine, some of the patients can not tolerate these therapies or fail to respond. More alternatives are now needed for the treatment of the disease, particularly those that are less invasive and specifically target the dilation of cerebral vessels. We have developed papaverine-gelatin microspheres that can be implanted intracranially at the time of surgery for aneurysm clipping, and confirmed that controlled releasing of papaverine is appropriate for the prevention of the vessel wall following subarachnoid hemorrhage. Methods： Papaverine-gelatin microspheres were injected into the magna cistern of rabbits by injecting their own artery blood into the cistern. The basilar artery diameters and vessel walls of the rabbits were observed under the transmission electron microscope 7 days after hemorrhage to evaluate the efficacy of papaverine-gelatin microspheres in preventing cerebral vasospasm. Results： The treatment with papaverine-gelatin microspheres resulted in a significant decrease in basilar artery vasospsasm as compared with the untreated group （ [ 0.92 ± 0.25 ] mm versus [ 0.52 ± 0.24 ] mm, P 〈 0.05） or the blank gelatin microsphere group （ [ 0.92 ±0.25 ] mm versus [ 0.46 ± 0. 16 ] mm, P 〈 0.05 ）. The vessel wall exhibited no significant pathological changes in the treatment group. Conclusion ： Intrathecal injection of papaverine-gelatin microspheres was a safe and effective strategy for both the treatment of SAH-indueed cerebral vasospasm and the prevention of the vessel wall in vivo.