【摘要】 目的 :探讨大剂量甲基强地松龙对慢性脑血管痉挛的作用机制。方法 :将成年犬随机分成大剂量甲基强地松龙 (MP ,10mg/kg)治疗组和对照组 ,治疗组和对照组又根据犬脑血管痉挛动态发展过程中不同阶段各分为A ,B ,C ,D 4个小组。通过枕大池二次注血法建立犬脑血管痉挛模型 ,经脑血管造影观察犬脑血管痉挛的动态发展过程。应用酶联免疫生化技术检测各组犬基底动脉血管平滑肌细胞胞膜蛋白激酶C(PKC)活性。应用体外血管张力性研究方法观察PKC激活剂 (phorobol12 myristate 13 acetate ,PMA)和高钾溶液对血管张力的影响 ,及甲基强地松龙对PMA和高钾溶液引起的血管张力的影响。结果 :经脑血管造影证实该剂量甲基强地松龙明显减轻了实验性脑血管痉挛的严重程度 ,与对照组相比 ,PKC活性在大剂量甲基强地松龙治疗组没有明显增高。体外血管张力性研究显示甲基强地松龙没有影响高钾引起的血管张力变化 ,相反 ,却明显抑制了PKC的激活剂PMA引起的血管张力性收缩。结论 :大剂量甲基强地松龙能够明显减轻脑血管痉挛程度 ,这种作用是通过抑制血管平滑肌细胞PKC活性 ,而不是作为Ca2 + 拮抗剂来发挥防治脑血管痉挛的发生发展更多还原

【Abstract】 Objective: The purpose of this study was to further clarify the pharmacological mechanism of methylprednisolone (MP) on cerebral vasospasm after subarachnoid hemorrhage. Methods: The dogs were randomly divided into 2 groups: a non treated group and a group treated with high dose MP. The 2 groups were further divided into A, B, C and D groups, depending on the progression of vasospasm. Using a "two hemorrhage" canine model, progression of angiographic vasospasm was assessed in the 2 groups. The MP (10 mg/kg) was intravenously injected after the first injection of blood, and the same dose was injected every 12 hours until the 7th day. Activities of protein kinase C (PKC) in canine basilar arteries were measured with a non radioisotopic protein kinase assay kit in various groups during the course of vasospasm. In the isometric tension study, the effects of MP on tensions induced by PMA (phorbol 12 myristate 13 acetate,PMA:one of PKC activators) and high K + solution were also evaluated. Results: The MP significantly reduced angiographic severity of vasospasm. In the treated group, PKC activity of the artery was not enhanced compared with the non treated group at any time. The MP inhibited the tonic contraction induced by PMA, but not by high K + solution. Conclusion: These results suggest that MP can prevent vasospasm through inhibition of PKC activity, but does not work as a Ca 2+ channel blocker.更多还原