Chen Duo, Nishizawa Shigeru, Yokota Naoki, Ohta Seiji, Yokoyama Tetsuo, Namba Hiroki
Department of Neurosurgery, Hamamatsu University School of Medicine, 3600 Handacho, Hamamatsu, Shizuoka 431-3192, Japan.
Neurol Res. 2002 Mar;24(2):215-22. doi: 10.1179/016164102101199639.
We have previously shown that the inflammatory process after subarachnoid hemorrhage causes vasospasm. The efficacy of methylprednisolone by suppression of the inflammatory process has been reported, although pharmacological mechanisms have not been clarified. The purpose of this study was to investigate the pharmacological mechanism of methylprednisolone on vasospasm. Using the 'two-hemorrhage' canine model, progression of angiographic vasospasm was assessed in nontreated and treated groups with methylprednisolone. Methylprednisolone 10 mg kg-1 was injected i.v. after the first injection of blood, and the same dose was injected every 12 h until day 7. Protein kinase C (PKC) activity of canine basilar arteries in both groups was measured during the course of vasospasm. In the isometric tension study, the effect of methylprednisolone on tensions induced by phorbol 12-myristate 13-acetate (PMA), or high-K+ solution, was also evaluated. Methylprednisolone significantly reduced severity of vasospasm. In the treated group, PKC activity was not enhanced compared with the nontreated group at any point. Methylprednisolone inhibited tonic tension induced by PMA, but not that induced by high-K+ solution. We conclude that methylprednisolone prevents severity of vasospasm through inhibition of PKC activation, but does not work as a Ca2+ channel blocker.
我们之前已经表明蛛网膜下腔出血后的炎症过程会导致血管痉挛。尽管尚未阐明其药理机制，但已有报道称甲基强的松龙通过抑制炎症过程具有疗效。本研究的目的是探讨甲基强的松龙对血管痉挛的药理机制。使用“两次出血”犬模型，在未治疗组和甲基强的松龙治疗组中评估血管造影血管痉挛的进展。在首次注入血液后静脉注射10mg/kg甲基强的松龙，并且每12小时注射相同剂量直至第7天。在血管痉挛过程中测量两组犬基底动脉的蛋白激酶C（PKC）活性。在等长张力研究中，还评估了甲基强的松龙对佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）或高钾溶液诱导的张力的影响。甲基强的松龙显著降低了血管痉挛的严重程度。在治疗组中，与未治疗组相比，在任何时间点PKC活性均未增强。甲基强的松龙抑制了PMA诱导的强直张力，但未抑制高钾溶液诱导的强直张力。我们得出结论，甲基强的松龙通过抑制PKC激活来预防血管痉挛的严重程度，但不作为钙通道阻滞剂起作用。
