胡椒碱预防实验性家兔SAH后迟发性脑血管痉挛

Effect of piperine for preventing on delayed cerebral vasospasm following experimental subarachnoid hemorrhage in rabbit

目的观察胡椒碱对蛛网膜下腔出血(SAH)后迟发性脑血管痉挛是否具有预防作用,并对其可能的作用机制进行初步探讨。方法将新西兰大白兔32只随机分为4组(n=8),A组(假注血组):只接受枕大池穿刺而不注血;B组(SAH组):经枕大池穿刺2次注血的方法,制作脑血管痉挛模型;C组(SAH+胡椒碱组):自第1次穿刺日始,静脉给予胡椒碱(20 mg/kg,溶媒0.5 mL/kg),每日1次;D组(SAH+溶媒组):静脉注射给予胡椒碱溶媒(0.5 mL/kg)。在第1次穿刺后的第7天处死,测定基底动脉内径、内径与血管壁厚度之比(D/T);用免疫组化法检测血管壁ET-1、eNOS表达。结果与A组比较,B组血管痉挛明显、血管壁ET-1表达增多e、NOS表达减少。C组分别与B组、D组比较,血管痉挛明显缓解(P<0.01),其血管壁上ET-1表达明显减少(P<0.05),eNOS在内皮细胞表达相对增多(P<0.05)。D组血管痉挛无明显缓解,血管壁ET-1、eNOS表达与SAH组无显著差异。结论胡椒碱(20 mg/kg)对蛛网膜下腔出血后迟发性脑血管痉挛有预防作用,其抗血管痉挛作用可能与胡椒碱抑制ET-1、促进eNOS活性有关。

Objective To observe whether piperine has the ability to prevent delayed cerebral vasospasm （DCVS） after subarachnoid hemorrhage （SAH）. Methods Thirty-two New Zealand white rabbits were divided into four groups randomly （n = 8）. Group A （shamed-injecting blood）： Puncture was completed without injecting blood into the cistema magna; Group B （SAH） ： DCVS model was made with two-hemonhage of SAH by injecting autologous arterial blood into the cistema magna; Group C （SAH ＋ piperine） ： Piperine （piperine 20 mg/kg, solvent 0.5 mL/kg） was intravenously administrated daily since day 0 after first injection. Group D （SAH ＋ DMSO） ： The solvent （0.5 mL/kg） was gave by i. v. for DCVS models. All animals were sacrificed at day 7 after the first injection. The internal diameter and D/T （internal diameter/wall thickness） values of basilar artery （BA） were measured. The expression of ET-1 and eNOS in arterial wall of BA at day 7 was collected via immunohistochemistry method. Results The severe vasospasm of BA, over expression of ET-1 and diminished expression of eNOS in group B were found vs group A. The vasospasm of BA in group C was obviously alleviated in comparison with it in group B and D, respectively （P 〈 0.01 ） and similar to that in group A. The expression of ET-1 in BA of group C was significantly decreased vs that of group B and D; respectively （ P 〈 0.05）. On the contrary, that of eNOS was significantly increased （ P 〈 0.05）. All of those in group D were same as that in group B. Conclusions Piperine （20 mg/kg） has a pharmaceutical action to attenuted DCVS following subarachnoid hemorrhage in rabbit, which maybe has some relations with the effect of piperine to protect the activity of eNOS and reduce production of ET-1.