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目的研究胡椒碱对实验性蛛网膜下腔出血后迟发性脑血管痉挛的作用机理。方法将新西兰白兔随机分为4组,每组12只。假手术组动物仅做枕大池假穿刺假注血,其余受试动物采用经枕大池穿刺2次注入自体动脉血的方法制作迟发性脑血管痉挛模型。自第1次注血始,生理盐水组动物经耳缘静脉注入生理盐水0．5ml/kg,依同样方法,胡椒碱溶媒组、胡椒碱组动物分别注入等量的胡椒碱溶媒、胡椒碱注射液20mg/kg,1次/d,直至第6天。各组受试动物在第7天时分两批处死,将脑组织连同基底动脉及其分支迅速取出,半数标本供组织学和TNF-α、IL-1β、IL-6等炎性细胞因子免疫组化观察,半数标本用RT-PCR的方法测定上述炎性细胞因子mRNA表达变化,用电泳迁移率变动分析法(EMSA)进行血管细胞核内NF-kB活性评价。结果与假手术组动物基底动脉正常血管形态相比,生理盐水组和胡椒碱溶媒组动物均有明显血管痉挛,血管壁上NF-kB活性、TNF-α、IL-1β和IL-6表达明显增高；而胡椒碱组动物血管痉挛得到明显缓解,血管壁上NF-kB活性、TNF-α、IL-1β和IL-6表达明显降低(P＜0．05)。结论胡椒碱可能通过抑制血管壁上NF-kB活性、下调TNF-α、IL-1β和IL-6的表达而发挥缓解蛛网膜下腔出血后迟发性脑血管痉挛作用。
Objective To study the mechanism of piperine on delayed cerebral vasospasm after experimental subarachnoid hemorrhage. Methods New Zealand white rabbits were randomly divided into 4 groups, 12 in each group. The animals in the sham-operation group were only given pseudo-puncture puncture, and the rest of the animals were made into the model of delayed-onset cerebral vasospasm by injecting autologous arterial blood twice through the puncture of large occipital cistern. From the beginning of the first injection of blood, the animals in the saline group were infused with 0.5 ml / kg of physiological saline via the ear vein. According to the same method, the animals in the piperine and piperine groups were injected with the same amount of piperine and piperine Liquid 20mg / kg, 1 time / d, until the first 6 days. The test animals in each group were sacrificed in two batches on the seventh day, and the brain tissues were rapidly removed along with the basilar artery and its branches. Half of the specimens were collected for histology and immunization with inflammatory cytokines such as TNF-α, IL-1β and IL-6 The changes of mRNA expression of the above inflammatory cytokines were measured by semi-quantitative RT-PCR. The activity of NF-κB in vascular nucleus was evaluated by electrophoretic mobility shift assay (EMSA). Results Compared with sham group, the animals in both normal saline group and piperine group had obvious vasospasm, NF-κB activity, and the expression of TNF-α, IL-1β and IL-6 were significantly increased (P <0.05). However, piperine group was significantly relieved of vasospasm and the expression of NF-κB, TNF-α, IL-1β and IL-6 in vessel wall were significantly decreased (P <0.05). Conclusion Piperine can relieve the delayed cerebral vasospasm after subarachnoid hemorrhage by inhibiting the activity of NF-κB on the vascular wall and down-regulating the expression of TNF-α, IL-1β and IL-6.