硝酸酯类药对大鼠蛛网膜下腔出血后脑血管痉挛影响的研究

The influence of mononitrate ester healer on vasospasm and cerebral ischemia after SAH in rats

目的探讨硝酸酯类药物对蛛网膜下腔出血(SAH)大鼠脑血管平滑肌内一氧化氮含量、脑动脉痉挛以及缺血性脑损伤的影响。方法采用自体动脉血注入大鼠枕大池的方法制备SAH模型。将36只雄性Wistar大鼠随机分为4组,每组9只。A组正常组;B组SAH组;C组SAH给予尼莫地平组;D组SAH给予单硝酸异山梨酯组。利用多普勒超声观察各模型组的脑动脉血流量,检测大鼠脑动脉组织匀浆内的一氧化氮浓度,一氧化氮合酶(NOS)、环磷酸鸟苷(cGMP)含量,观察海马角神经元的超微结构及BAX、BCL2阳性细胞表达的数量。结果①单硝酸异山梨酯与尼莫地平一样,均可降低大鼠脑血管阻力,改善SAH所致的脑血管痉挛。②D组的一氧化氮含量明显高于其他组(P<0.05)。③D组大鼠的cGMP含量为(225±45)pmol/ml,B组为(108±31)pmol/ml,C组为(112±29)pmol/ml,与D组比较,均P<0.05;A组为(211±45)pmol/ml,与D组比较,差异无显著意义(P>0.05)。④BAX阳性细胞数的变化A组为0.30±0.03,D组为0.50±0.04,C组为0.57±0.07,B组为0.67±0.05。结论硝酸酯类药物通过NOcGMP血管舒张通路,以解除SAH后的脑血管痉挛,而改善脑血流量。

Objective To discuss the effect of mononitrate ester he al er on chronic cerebral vasospasm after subarachnoid hemorrhage (SAH) through inc reasing in the local availability of nitric oxide (NO). We tested the ability of the long-acting, water-soluble, NO donor-isosorbide mononitrate and observed its influence on vasospasm and cerebral ischemia after SAH. Methods SAH was induced in rats via blood injection into the cisterna magna .3 6 rats were randomly divided into four groups, normal controlled group (group A) , SAH group (group B), SAH+nimodipin group (group C),and SAH+ isosorbide mono nitrate group (group D). Doppler ultrasonography was used for monitoring the cer ebral blood flow velocities in every group after SAH. Levels of NO,NOS and cycli c guanosine monophosphate (cGMP) were measured in cerebral arteries on day 6 aft er SAH.And to observe the expression of BAX/BCL-2 protein and the ultrastructur e of hippocampus. Results ①Isosorbide mononitrate, as nimodip ine can increase cerebral blood flow velocities after SAH. ②Level of NO in grou p D was higher than other groups(P < 0.05) . ③The level of cGMP in group D (225±45) pmol/ml was higher than group B(108± 31) pmol/ml and the level of cGMP in groups C (112±29) pmol/ml groups, had no s tatistic difference compared with group A (211±45) pmol/ml. ④The expression of BAX was increased according to following order: group A 0.30±0.03,group D 0 .50±0.04, group C 0.57±0.07 and group B 0.67±0.05 (P < 0.05). Conclusion Isosorbide mononitrate i s able to alleviate chronic vasospasm after SAH via NO-cGMP mediated relaxation pathways.