胰岛素联合依达拉奉治疗对实验性蛛网膜下腔出血后脑血管痉挛的影响

Effect of insulin combined with Edaravone therapy on cerebral vasospasm after experimental subarachnoid hemorrhage

目的探讨胰岛素联合依达拉奉治疗对实验性蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的影响。方法健康新西兰白兔40只,随机分为假手术组(8只)、SAH组(10只)、胰岛素组(10只)、胰岛素+依达拉奉组(12只)。采用兔枕大池2次注血法建立SAH模型。第1次注血后30min,胰岛素组及胰岛素+依达拉奉组皮下注射胰岛素0.2U/kg,每日3次,共7d;同时,胰岛素+依达拉奉组经耳缘静脉推注依达拉奉注射液0.5mg/kg,每日2次,共7d。制模第7d测量各组基底动脉横截面积以评估CVS的程度,观察基底动脉的病理学变化;免疫组化染色测定血管内皮细胞胰岛素受体(InRa)的表达。结果胰岛素+依达拉奉组基底动脉横截面积[(0.46±0.3)mm2]与假手术组[(0.48±0.4)mm2]比较差异无统计学意义;SAH组[(0.25±0.3)mm2]及胰岛素组[(0.30±0.3)mm2]明显小于假手术组(均P<0.05);与假手术组比较,血管内皮细胞InRa在SAH组和胰岛素组的表达明显下调(均P<0.05);胰岛素+依达拉奉组与假手术组比较差异无统计学意义。病理学观察显示:假手术组内皮细胞光滑,血管壁无增厚;SAH组及胰岛素组血管壁明显增厚,内皮细胞皱缩;胰岛素+依达拉奉组管壁稍厚,内皮细胞舒展无皱缩。结论胰岛素与依达拉奉联合运用可有效缓解兔实验性SAH后的CVS。

Objective To investigate the effect of insulin combined with Edaravone therapy on delayed cerebral vasospasm （CVS） ＇after experimental subarachnoid hemorrhage （SAH）. Methods 40 New Zealand white rabbits were randomly separated into sham-operated group （n = 8）, SAH group （n = 10）, insulin group （n = 10） and insulin ± Edaravone group（n = 12）. SAH models were made by injecting blood twice into cisterna magna. 30 min later of the first blood injected, the insulin 0.2 U/kg was subcutaneous injected in insulin group and insulin ± Edaravone group, 3 times daily for 7 d; while, the insulin ± Edaravone group received Edaravone 0. 5 mg/kg （ intravenous injected in ear vein） twice a day for 7 d. 7 d after the model made, the basilar artery cross sectional area was measured and the pathological changes were obseved to estimate the degree of CVS. The expression of insulin receptor （InRa） in vascular endothelial cell was detected by immunohistocbemical staining. Results The basilar artery cross sectional area between insulin ± Edaravone group [ （0.46 ± 0.3 ） mm^2 ] and the sham-operated group[ （0.48 ± 0.4 ）mm2] was no significant difference; but they were obviously bigger than those in SAH group [ （0.25 ± 0.3 ） mm^2 ] and the insulin group [ （ 0.30 ± 0.3 ） mm^2 ] （ all P 〈 0. 05 ）. Compared to sham-operated group, the vascular endothelial cell lnRa expression in SAH group and the insulin group were significantly reduced （ all P 〈 0.05 ） , but in insulin ± Edaravnne group was no significant difference. The pathological examination showed ： the endotheliocyte was smooth and the vessel wall was no thickened in the sham-operated group; in the SAH group and the insulin group,the endotheliocyte became corrugativus and the vessel wall became obviously thickened; in the insulin ± Edaravone group, the endotheliocyte did not corrugativus and the vessel wall was thickened slightly. Conclusion The insulin combined with Edaravone therapy can effectively improve CVS after experimental SAH.